Παιδιατρική | Τόμος 71 • Τεύχος 4 • Ιούλιος - Αύγουστος 2008

Pediatri Jul-Aug 08

30-07-08

15:51

¢ÈÌËÓÈ·›· ¤Î‰ÔÛË Ù˘ EÏÏËÓÈ΋˜ ¶·È‰È·ÙÚÈ΋˜ EÙ·ÈÚ›·˜ ¶Úfi‰ÚÔ˜ ∞. ∫ˆÓÛÙ·ÓÙfiÔ˘ÏÔ˜ ™˘ÓÙ·ÎÙÈ΋ EÈÙÚÔ‹ ¢È¢ı˘ÓÙ‹˜ ™‡ÓÙ·Í˘ ∫. ™ÙÂÊ·Ó›‰Ë˜ M¤ÏË ™. ∞Ó‰ÚÔÓ›ÎÔ˘ ª. ∞ÓıÚ·ÎfiÔ˘ÏÔ˜ ¶. ∞˘ÁÔ˘ÛÙ›‰Ô˘-™·‚‚ÔÔ‡ÏÔ˘ °. µ·ÚÏ¿Ì˘ ∂. °·Ï·Ó¿Î˘ §. £ˆÌ·˝‰Ô˘ ª. ∫·Ó¿ÚÈÔ˘ A. K·ÙÙ¿Ì˘ ™. K›ÙÛÈÔ˘-∆˙¤ÏË ∞. ¶··‰ÔÔ‡ÏÔ˘ µ. ¶··Â˘·ÁÁ¤ÏÔ˘ ∞. ™È·ÌÔÔ‡ÏÔ˘-ª·˘Ú›‰Ô˘ ∞. ™˘Ú›ÁÔ˘-¶··‚·ÛÈÏ›Ԣ ∂. ÷ÚÌ·Ó‰¿ÚË ÀÔ‚ÔÏ‹ ∂ÚÁ·ÛÈÒÓ e-mail: hps@ath.forthnet.gr

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¶·È‰È·ÙÚÈ΋ ∆fiÌÔ˜ 71 ñ ∆‡¯Ô˜ 4 ñ IÔ‡ÏÈÔ˜-∞‡ÁÔ˘ÛÙÔ˜ 2008

¶ÂÚȯfiÌÂÓ· ∞¡∞™∫O¶∏™∂π™

¶ƒ∞∫∆π∫√ £∂ª∞

255 °ÂÓÂÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÔÍ›·˜ ÏÂÌÊÔ‚Ï·ÛÙÈ΋˜ Ï¢¯·ÈÌ›·˜ Ù˘ ·È‰È΋˜ ËÏÈΛ·˜ º. ∆˙ÈÊ‹, ∞. KÔÏȷϤÍË, ∫. ™·Ï·‚Ô‡Ú·, ™. ∫›ÙÛÈÔ˘, ∞. ª·‡ÚÔ˘

304 ™‡Ó‰ÚÔÌÔ ·ÈÊÓ›‰ÈÔ˘ ‚ÚÂÊÈÎÔ‡ ı·Ó¿ÙÔ˘: ¶·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ Î·È ÓÂÒÙÂÚ˜ ηÙ¢ı˘ÓÙ‹ÚȘ Ô‰ËÁ›Â˜ ™. ™ÙÂÊ·Ó¿ÎË, ∞. ∆ÛÈÏÈÌÈÁοÎË

263 ∫˘ÙÙ·ÚÔÁÂÓÂÙÈο Â˘Ú‹Ì·Ù· ÛÙȘ Ï¢¯·È̛˜ Ù˘ ·È‰È΋˜ ËÏÈΛ·˜ ∞. °·ÏÏ¿-µÔ˘Ì‚Ô˘Ú¿ÎË 271 ªË Ù˘¯·›· ·‰Ú·ÓÔÔ›ËÛË ÙÔ˘ ÃÚˆÌÔÛÒÌ·ÙÔ˜ Ã: ÎÏÈÓÈΤ˜ ÂÈÙÒÛÂȘ ÙÔ˘ Ê·ÈÓÔ̤ÓÔ˘ skewing ÛÙ· ·È‰È¿ Î·È ÙÔ˘˜ ÂÓ‹ÏÈΘ °. §·‚Ú¿ÓÔ˜, ƒ. ∞ÁÁÂÏÔÔ‡ÏÔ˘

√‰ËÁ›Â˜ ÚÔ˜ ÙÔ˘˜ Û˘ÁÁÚ·Ê›˜: http://www.e-child.gr/Instructions_ to_Authors_GR.pdf

277 ªÈÎÚÔÏÈı›·ÛË fiÚ¯ÂˆÓ ¢. £ˆÌ¿˜, ∂. µÏ·¯Ô··‰ÔÔ‡ÏÔ˘, µ. ¶··‰¿Î˘

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∂ƒ∂À¡∏∆π∫∂™ ∂ƒ°∞™π∂™

∂È̤ÏÂÈ· ÂÏÏËÓÈÎÒÓ ÎÂÈÌ¤ÓˆÓ M. ¡·ÙÛÔ˘Ï›‰Ô˘

283 ∆È ÚÔηÏ› ÙË ¯ˆÏfiÙËÙ· ÙÔ˘ ∏Ê·›ÛÙÔ˘; ∂. ª·˙ÔÔ‡ÏÔ˘-∫˘Úηӛ‰Ô˘

EÈ̤ÏÂÈ· ·ÁÁÏÈÎÒÓ ÎÂÈÌ¤ÓˆÓ ™. ¡¿ÎÔ˘

291 Age-related serial plasma citrulline levels in preterm neonates H.P. Ioannou, E. Diamanti, Z. Tsampoura, V. Drossou-Agakidou, P. Augoustides-Savvopoulou

EΉfiÙ˘ K. °ÚÈ‚¤·˜ ™˘ÓÙÔÓÈÛÙ‹˜ ∂ΉfiÛˆ˜ E¶I™THMONIKE™ EK¢O™EI™ E.¶.E. ¶ÈÂÚ›·˜ 1∞ 144 51 MÂÙ·ÌfiÚʈÛË TËÏ.: 210 87 78 810 Fax: 210 87 78 822 I‰ÈÔÎÙ‹Ù˘ EÏÏËÓÈ΋ ¶·È‰È·ÙÚÈ΋ EÙ·ÈÚ›·© Mȯ·Ï·ÎÔÔ‡ÏÔ˘ 92 Aı‹Ó· 115 28 TËÏ.: 210 7771 140 210 7771 663 Fax: 210 7758 354 e-mail: hps@ath.forthnet.gr EÙ‹ÛÈ· ™˘Ó‰ÚÔÌ‹: 40 € EȉÈ΢fiÌÂÓÔÈ, ºÔÈÙËÙ¤˜: 20 € ∫ˆ‰ÈÎfi˜ ¢È‡ı˘ÓÛ˘ ∂ÔÙ›·˜ ªª∂: 3889

ISSN 0377-2551

296 Immune status and immune recovery in children with lymphoma at the end of treatment (chemotherapy and/or radiotherapy) and on follow-up evaluation S. Kosmidis, A. Pourtsidis, D. Bouhoutsou, M. Baka, M. Varvoutsi, D. Doganis, C. Kallergi, N. Douladiris, M. Synodinou, F. Saxoni-Papageorgiou, H. Vasilatou-Kosmidis 301 ∫ÏÈÓÈÎÔ-ÂȉËÌÈÔÏÔÁÈο ‰Â‰Ô̤ӷ Û ÓÔÛËÏ¢fiÌÂÓ· ·È‰È¿ Ì ÔÍ›· Á·ÛÙÚÂÓÙÂÚ›Ùȉ· ·fi Èfi ƒfiÙ· (1984-2007) O. TÛÈ¿ÙÛÈÔ˘, √. ¶··ÁÈ·ÓÓÔÔ‡ÏÔ˘, ∞ÈÎ. ™·Ú·ÓÙÔÔ‡ÏÔ˘, Ã. ∞ÏÂÍ·Ó‰Ú¿ÙÔ˜, ¢. K·Ú·Ì·ÍfiÁÏÔ˘, π. K·‚·ÏÈÒÙ˘

∂¡¢π∞º∂ƒ√À™∂™ ¶∂ƒπ¶∆ø™∂π™ 311 ™‡Ó‰ÚÔÌÔ ·Ó·ÛÙÚ¤„ÈÌ˘ Ô›ÛıÈ·˜ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜ (PRES): ÂÚÈÁÚ·Ê‹ ‰‡Ô ÂÚÈÙÒÛÂˆÓ Î·È ·Ó·ÛÎfiËÛË Ù˘ ‚È‚ÏÈÔÁÚ·Ê›·˜ µ. ∞ÛÎËÙ‹, ∞. ªËÙÛÈÒÓË, ™. ª·ÛÙÚÔÁÈ¿ÓÓË, ¶. °Ô˘ÚÙ˙ÂÏ›‰Ë˜, π. ¡›Î·˜, ∫. ™ÙÂÊ·Ó›‰Ë˜ 317 ™‡Ó‰ÚÔÌÔ McCune-Albright. ¶ÂÚÈÁÚ·Ê‹ ÂÚ›ÙˆÛ˘ µ. ∞ÁÁÂÏ¿ÎÔ˘, ∫. ∞Ó˘Ê·ÓÙ¿Î˘, ∞. ™Ù·Ì·Ù¿ÎË, ∂. ∫fiÎÔÚË, ¶. ¶··¯ÈÏϤˆ˜, Ã. ÷Ù˙Ë·ı·Ó·Û›Ô˘† ∫§π¡π∫√ ∫√Àπ∑ 323 ∞ÁfiÚÈ 16 ÌËÓÒÓ Ì ¯ˆÏfiÙËÙ· ¡. ª·ÚΤ·˜, π. ¶··¯Ú‹ÛÙÔ˜ ™À¡∆√ª∞ ¶∞π¢π∞∆ƒπ∫∞ ¡∂∞ 324 ¡¤· ÁÈ· Ù· ÂÌ‚fiÏÈ· 2008 E. °·Ï·Ó¿Î˘ ¡∂∞ ∞¶√ ∆√ ¢π∞¢π∫∆À√ 327 H ÈÛÙÔÛÂÏ›‰· ÙÔ˘ µ·ÛÈÏÈÎÔ‡ ∫ÔÏÂÁ›Ô˘ ¶·È‰È·ÙÚÈ΋˜ Î·È ¶·È‰È΋˜ ÀÁ›·˜ ∫. ™ÙÂÊ·Ó›‰Ë˜

Pediatri Jul-Aug 08

30-07-08

15:52

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Bimonthly Publication of the Greek Paediatric Society

Paediatriki

President A. Constantopoulos Editorial Board Editor-in-Chief C. Stefanidis Members S. Andronikou ª. ∞nthracopoulos P. Augoustides-Savvopoulou G. Varlamis ∂. Galanakis L. Thomaidou M. Kanariou A. Kattamis S. Kitsiou-Tzeli ∞. Papadopoulou V. Papaevagelou A. Siamopoulou-Mavridou A. Syrigou-Papavasiliou E. Charmandari Manuscript submission e-mail: hps@ath.forthnet.gr Instructions to authors: http://www.e-child.gr/paediatriki/ iae.pdf Manuscript Editing Greek Editing M. Natsoulidou English Editing S. Nakou Publisher K. Griveas Publishing Coordinator SCIENTIFIC PUBLICATIONS Ltd 1∞ Pierias St. GR - 144 51, Metamorfossi Tel.: +30 210 87 78 810 Fax: +30 210 87 78 822 Owner Greek Paediatric Society© 92 Michalakopoulou St. GR - 115 28, Athens Tel.: +30 210 7771 140 +30 210 7771 663 Fax: +30 210 7758 354 e-mail: hps@ath.forthnet.gr Annual Subscription All foreign countries: US $ 50

Volume 71 ñ Number 4 ñ July-August 2008

Contents REVIEW ARTICLES

PRACTICAL ISSUE

255 Genetic studies in childhood acute lymphoblastic leukaemia F. Tzifi, A. Kolialexi, K. Salavoura, S. Kitsiou, A. Mavrou

304 Sudden infant death syndrome: Risk factors and the latest guidelines S. Stefanaki, A. Tsilimigkaki

263 Cytogenetic abnormalities in leukaemias of childhood ∞. Galla-Voumvouraki

CASE REPORTS

271 Non-random X inactivation: clinical consequences of the skewing effect G. Lavranos, R. Angelopoulou 277 Testicular microlithiasis D. Thomas, ∂. Vlahopapadopoulou, V. Papadakis ORIGINAL ARTICLES 283 What causes the lameness of Hephaestus? ∂. µazopoulou-∫yrkanidou 291 Age-related serial plasma citrulline levels in preterm neonates H.P. Ioannou, E. Diamanti, Z. Tsampoura, V. Drossou-Agakidou, P. Augoustides-Savvopoulou 296 Immune status and immune recovery in children with lymphoma at the end of treatment (chemotherapy and/or radiotherapy) and on follow-up evaluation S. Kosmidis, A. Pourtsidis, D. Bouhoutsou, M. Baka, M. Varvoutsi, D. Doganis, C. Kallergi, N. Douladiris, M. Synodinou, F. Saxoni-Papageorgiou, H. Vasilatou-Kosmidis 301 Clinico-epidemiological data on children hospitalized with acute gastroenteritis due to rotavirus (1984-2007) O. Tsiatsiou, √. Papagiannopoulou, Aik. Sarantopoulou, C. Alexandratos, D. Karabaxoglou, π. Kavaliotis

311 Posterior reversible encephalopathy syndrome: a report of two cases and literature review V. Askiti, ∞. Mitsioni, S. ªastroyianni, P. Gourtzelidis, π. Nikas, C. Stefanidis 317 McCune-Albright syndrome. A case report V. Aggelakou, K. Anyfantakis, K. Stamataki, H. Kokori, P. Papachileos, C. Hadjiathanassiou† CLINICAL QUIZ 323 16-month old boy with lameness N. Markeas, I. Papachristos PAEDIATRIC NEWS IN BRIEF 324 Update on vaccination 2008 E. Galanakis NEWS FROM THE INTERNET 327 The web page of the Royal College of Paediatrics and Child Health (RCPCH) C. Stefanidis

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™À¡∆∞∫∆π∫∏ E¶π∆ƒ√¶∏

EDITORIAL BOARD

¢È¢ı˘ÓÙ‹˜ ™‡ÓÙ·Í˘

Editor-in-Chief

∫ˆÓÛÙ·ÓÙ›ÓÔ˜ ™ÙÂÊ·Ó›‰Ë˜, ∞ı‹Ó·

Constantinos Stefanidis, Athens

∂ȉÈÎÔ› ™˘ÓÙ¿ÎÙ˜

Section Editors

™Ù¤ÏÏ· ∞Ó‰ÚÔÓ›ÎÔ˘, ¡ÂÔÁÓÔÏÔÁ›·, πˆ¿ÓÓÈÓ·

Stella Andronikou, Neonatology, Ioannina

ªÈ¯·‹Ï ∞ÓıÚ·ÎfiÔ˘ÏÔ˜, ¶Ó¢ÌÔÓÔÏÔÁ›·, ¶¿ÙÚ·

Michael Anthracopoulos, Pneumonology, Patras

¶ÂÚÛÂÊfiÓË ∞˘ÁÔ˘ÛÙ›‰Ô˘-™·‚‚ÔÔ‡ÏÔ˘, MÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·, £ÂÛÛ·ÏÔÓ›ÎË

Persefoni Avgoustides-Savvopoulou, Metabolic Disorders, Thessaloniki

°ÂÒÚÁÈÔ˜ µ·ÚÏ¿Ì˘, ∫·Ú‰ÈÔÏÔÁ›·, £ÂÛÛ·ÏÔÓ›ÎË

George Varlamis, Cardiology, Thessaloniki

∂ÌÌ·ÓÔ˘‹Ï °·Ï·Ó¿Î˘, ∏ıÈ΋ Î·È ¢ÂÔÓÙÔÏÔÁ›·, ∏Ú¿ÎÏÂÈÔ

Emmanouil Galanakis, Ethics and Deontology, Heraklion

§ˆÚ¤ÙÙ· £ˆÌ·˝‰Ô˘, ∞Ó·Ù˘ÍȷΤ˜ ‰È·Ù·Ú·¯¤˜, ∞ı‹Ó·

Loretta Thomaidou, Developmental Pediatrics, Athens

ª·Ú›· ∫·Ó¿ÚÈÔ˘, ∞ÓÔÛÔÏÔÁ›·, ∞ı‹Ó·

Maria Kanariou, Immunology, Athens

∞ÓÙÒÓ˘ ∫·ÙÙ¿Ì˘, ∞ÈÌ·ÙÔÏÔÁ›· - OÁÎÔÏÔÁ›·, ∞ı‹Ó·

Antonis Kattamis, Haematology - √ncology, Athens

™ÔÊ›· ∫›ÙÛÈÔ˘-∆˙¤ÏË, °ÂÓÂÙÈ΋, ∞ı‹Ó·

Sophia Kitsiou-Tzeli, Genetics, Athens

∞ÏÂÍ¿Ó‰Ú· ¶··‰ÔÔ‡ÏÔ˘, °·ÛÙÚÂÓÙÂÚÔÏÔÁ›· - ¢È·ÙÚÔÊ‹, ∞ı‹Ó·

Alexandra Papadopoulou, Gastroenterology - Nutrition, Athens

µ·ÛÈÏÈ΋ ¶··Â˘·ÁÁ¤ÏÔ˘, §ÔÈ̈ÍÈÔÏÔÁ›·, ∞ı‹Ó·

Vassiliki Papaevagelou, Infectious Diseases, Athens

∞ÓÙÈÁfiÓË ™È·ÌÔÔ‡ÏÔ˘-ª·˘Ú›‰Ô˘, ƒÂ˘Ì·ÙÔÏÔÁ›·, πˆ¿ÓÓÈÓ·

Antigoni Siamopoulou-Mavridou, Rheumatology, Ioannina

∞ÓÙÈÁfiÓË ™˘Ú›ÁÔ˘-¶··‚·ÛÈÏ›Ԣ, ¡Â˘ÚÔÏÔÁ›·, ∞ı‹Ó·

Antigone Syrigou-Papavasiliou, Neurology, Athens

∂˘·ÁÁÂÏ›· ÷ÚÌ·Ó‰¿ÚË, ∂Ó‰ÔÎÚÈÓÔÏÔÁ›·, ∞ı‹Ó·

Evangelia Charmandari, Endocrinology, Athens

ª¤ÏË Ù˘ ¢ÈÂıÓÔ‡˜ ™˘ÓÙ·ÎÙÈ΋˜ ∂ÈÙÚÔ‹˜ ñ Members of the International Editorial Board Alexis Arzimanoglou, Paris, France

Peter Hoyer, Essen, Germany

Ellis D. Avner, Milwaukee, USA

Jan Janda, Prague, Czech Republic

Swati Bhave, New Delhi, India

Jan Kimpen, Ultrecht, Netherlands

Alberto Bissot, Panama, Panama

Craig B. Langman, Chicago, USA

David Branski, Jerusalem, Israel

John Manis, Boston, USA

Francesco Chiarelli, Chieti, Italy

Manuel Moya, Alicante, Spain

Chok-Wan Chan, Hong Kong, China

Hugh O'Brodovich, Toronto, Canada

Denis Daneman, Toronto, Canada

Ross Petty, Vancouver, Canada

Jochen Ehrich, Hannover, Germany

Willem Proesmans, Leuven, Belgium

Demetrius Ellis, Pittsburgh, USA

Jose Ramet, Antwerp, Belgium

Yoshikatsu Eto, Tokyo, Japan

Nikolai Shabalov, St. Petersburg, Russia

Richard N. Fine, Stony Brook, USA

Alan Sinaiko, Minneapolis, USA

Margaret C. Fisher, Philadelphia, USA

Nick J. Spencer, Coventry, UK

Raif Geha, Boston, USA

Alfred Tenore, Udine, Italy

Adenike Grange, Lagos, Nigeria

Alkis Togias, Bethesda, USA

Judith G. Hall, Vancouver, Canada

Eva Tsalikian, Iowa City, USA

Patricia Hamilton, London, UK

Catherine Weil-Olivier, Paris, France

Enver Hasanoglu, Ankara, Turkey

Max Zach, Graz, Austria

Christer Holmberg, Helsinki, Finland

Zheng-Yan Zhao, Hangzhou, China

Lewis B. Holmes, Boston, USA

Johannes Zschocke, Heidelberg, Germany

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Pediatri Jul-Aug 08

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∞ƒ£ƒ√ ™À¡∆∞•∏™

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EDITORIAL

∞Á·ËÙÔ› Û˘Ó¿‰ÂÏÊÔÈ, ™·˜ ¢¯·ÚÈÛÙԇ̠ÁÈ· ÙÔ Û˘Ó¯¤˜ ÂӉȷʤÚÔÓ Û·˜ ÁÈ· ÙËÓ “¶·È‰È·ÙÚÈ΋” Î·È ÁÈ· ÙÔÓ ·˘Í·ÓfiÌÂÓÔ ·ÚÈıÌfi ÂÚÁ·ÛÈÒÓ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È. £· ı¤Ï·Ì ӷ Û·˜ ÂÓËÌÂÚÒÛÔ˘Ì fiÙÈ Ù· Ó¤· ̤ÏË Ù˘ ™˘ÓÙ·ÎÙÈ΋˜ ∂ÈÙÚÔ‹˜ Â›Ó·È Ô Î‡ÚÈÔ˜ ªÈ¯·‹Ï ∞ÓıÚ·ÎfiÔ˘ÏÔ˜ (¶Ó¢ÌÔÓÔÏÔÁ›·), Ë Î˘Ú›· µ·ÛÈÏÈ΋ ¶··Â˘·ÁÁ¤ÏÔ˘ (§ÔÈ̈ÍÈÔÏÔÁ›·), Ë Î˘Ú›· ∞ÓÙÈÁfiÓË ™˘Ú›ÁÔ˘-¶··‚·ÛÈÏ›Ԣ (¡Â˘ÚÔÏÔÁ›·) Î·È Ë Î˘Ú›· ∂˘·ÁÁÂÏ›· ÷ÚÌ·Ó‰¿ÚË (∂Ó‰ÔÎÚÈÓÔÏÔÁ›·). ∏ ΢ڛ· ™˘Ú›ÁÔ˘-¶··‚·ÛÈÏ›Ԣ Î·È Ô Î‡ÚÈÔ˜ ∞ÓıÚ·ÎfiÔ˘ÏÔ˜ Û˘ÌÌÂÙ›¯·Ó Î·È ·Ï·ÈfiÙÂÚ· ÛÙË ™˘ÓÙ·ÎÙÈ΋ ∂ÈÙÚÔ‹ Ù˘ “¶·È‰È·ÙÚÈ΋˜”. ∏ ΢ڛ· ∞Ó‰ÚÈ·Ó‹ µ·˙·›Ô˘-°ÂÚ·ÛÈÌ›‰Ë, Ë Î˘Ú›· ∂˘ÛÙ·ı›· ∫·ÙÛ·ÚÔ‡-¶ÂÎÙ·Û›‰Ë, Ô Î‡ÚÈÔ˜ ¡ÈÎfiÏ·Ô˜ ¶··‰fiÔ˘ÏÔ˜ Î·È Ë Î˘Ú›· ª·Ú›˙· ∆ÛÔÏÈ¿-¶·Û·Ú¿ÎË ·Ô¯ÒÚËÛ·Ó ·fi ÙË ™˘ÓÙ·ÎÙÈ΋ ∂ÈÙÚÔ‹. £· ı¤Ï·Ì ӷ ÙÔ˘˜ ¢¯·ÚÈÛÙ‹ÛÔ˘Ì ÁÈ· ÙË Ì·ÎÚfi¯ÚÔÓË Î·È Ô˘ÛÈ·ÛÙÈ΋ Û˘Ì‚ÔÏ‹ ÙÔ˘˜. ªÂ ÙËÓ Â˘Î·ÈÚ›· ·˘Ù‹ ı· ı¤Ï·Ì ӷ Û·˜ ˘ÂÓı˘Ì›ÛÔ˘Ì fiÙÈ ÌÔÚ›Ù ӷ ÛÙ›ÏÂÙ ÛÙËÓ “¶·È‰È·ÙÚÈ΋” ÂÚˆÙ‹Ì·Ù· Ô˘ Û·˜ ··Û¯ÔÏÔ‡Ó ÛÙËÓ Î·ıËÌÂÚÈÓ‹ ÎÏÈÓÈ΋ Ú¿ÍË. ∆· ÂÚˆÙ‹Ì·Ù· ·˘Ù¿ ı· ·ÔÙÂϤÛÔ˘Ó Ù· ı¤Ì·Ù· ÁÈ· ÙË ÛÂÈÚ¿ ¿ÚıÚˆÓ: “ƒˆÙ‹ÛÙ ÙÔÓ ÂȉÈÎfi”. ªÂ ıÂÚÌÔ‡˜ ¯·ÈÚÂÙÈÛÌÔ‡˜,

∫ˆÓÛÙ·ÓÙ›ÓÔ˜ ™ÙÂÊ·Ó›‰Ë˜ ¢È¢ı˘ÓÙ‹˜ ™‡ÓÙ·Í˘

Dear colleagues, Thank you for your continuous interest in “Paediatriki” and the increasing number of submitted papers. We would like to inform you that Dr Michael Anthracopoulos (Pneumonology), Dr Vassiliki Papaevagelou (Infectious Diseases), Dr Antigone Syrigou-Papavasiliou (Neurology) and Dr Evangelia Charmandari (Endocrinology) are the new members of the Editorial Board. Dr Syrigou-Papavasiliou and Dr Anthracopoulos were formerly members of the Editorial Board of “Paediatriki”.

Dr Andriani Vazaiou-Gerasimidi, Dr Eustathia Katsarou-Pektasides, Dr Nicolaos Papadopoulos and Dr Marisa Tsolia withdrew from the Editorial Board. We would like to thank them for their longterm and important contribution.

On this occasion we would like to invite you to send us questions that arise from your every day practice. These questions will become the topics of the section: “Ask the expert”.

Warm greetings, Constantinos Stefanidis Editor-in-Chief

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REVIEW ARTICLE

255

°ÂÓÂÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÔÍ›·˜ ÏÂÌÊÔ‚Ï·ÛÙÈ΋˜ Ï¢¯·ÈÌ›·˜ Ù˘ ·È‰È΋˜ ËÏÈΛ·˜ º. ∆˙ÈÊ‹1, ∞. KÔÏȷϤÍË1, ∫. ™·Ï·‚Ô‡Ú·2, ™. ∫›ÙÛÈÔ˘1, ∞. ª·‡ÚÔ˘1 ¶ÂÚ›ÏË„Ë: H ÔÍ›· ÏÂÌÊÔ‚Ï·ÛÙÈ΋ Ï¢¯·ÈÌ›· (√§§) Â›Ó·È Ë ÈÔ Û˘¯Ó‹ Ï¢¯·ÈÌ›· Ù˘ ·È‰È΋˜ ËÏÈΛ·˜. ∏ Ù·ÍÈÓfiÌËÛ‹ Ù˘ Û هÔ˘˜ Î·È ˘ÔÙ‡Ô˘˜ Á›ÓÂÙ·È ÌÂ Û˘Ó‰˘·ÛÌfi ΢ÙÙ·ÚÔÏÔÁÈÎÒÓ, ·ÓÔÛÔÏÔÁÈÎÒÓ Î·È Î˘ÙÙ·ÚÔÁÂÓÂÙÈÎÒÓ ¯·Ú·ÎÙËÚÈÛÙÈÎÒÓ. √È ¯ÚˆÌÔÛˆÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ Ô‰ËÁÔ‡Ó Û ‰È·Ù·Ú·¯‹ Ù˘ ¤ÎÊÚ·Û˘ ÔÁÎÔÁÔÓȉ›ˆÓ ‹ ÔÁÎÔηٷÛÙ·ÏÙÈÎÒÓ ÁÔÓȉ›ˆÓ, Ù· ÔÔ›· ·›˙Ô˘Ó ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ·ÈÙÈÔ·ıÔÁ¤ÓÂÈ· Ù˘ ÓfiÛÔ˘. ∂ÈϤÔÓ, Ë ¤Ú¢ӷ ÛÙÔÓ ÙÔ̤· Ù˘ ÁÂÓÂÙÈ΋˜ ÙÔ˘ ηÚΛÓÔ˘ ¤¯ÂÈ Ó· ·ÚÔ˘ÛÈ¿ÛÂÈ ÏËıÒÚ· ÌÂÏÂÙÒÓ Ô˘ ‰ËÏÒÓÔ˘Ó fiÙÈ Ë ÓÂÔÏ·Û›· Â›Ó·È ÁÂÓÂÙÈ΋ ‰È·Ù·Ú·¯‹ Û Â›Â‰Ô ÛˆÌ·ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ. ™ÙËÓ ·Ó·ÛÎfiËÛË ·˘Ù‹ ·Ó·Ê¤ÚÔÓÙ·È Ù· ¯ÚˆÌÔÛˆÌÈο Î·È ÌÔÚȷο ¯·Ú·ÎÙËÚÈÛÙÈο Ù˘ √§§ Ô˘ ‚ÔËıÔ‡Ó ÛÙËÓ Î·Ù·ÓfiËÛË Ù˘ ‚ÈÔÏÔÁ›·˜ Ù˘ ÓfiÛÔ˘ Î·È ¤¯Ô˘Ó ÂÊ·ÚÌÔÁ‹ ÛÙË Û‡Á¯ÚÔÓË ‰È·ÁÓˆÛÙÈ΋. ∏ ÂÊ·ÚÌÔÁ‹ Ù˘ ªÔÚȷ΋˜ ∫˘ÙÙ·ÚÔÁÂÓÂÙÈ΋˜ ‰›ÓÂÈ Ó¤Â˜ ‰˘Ó·ÙfiÙËÙ˜ ÛÙËÓ ÂÚÁ·ÛÙËÚȷ΋ ‰ÈÂÚ‡ÓËÛË ·È‰ÈÒÓ Ì ·ÈÌ·ÙÔÏÔÁÈΤ˜ ηÎÔ‹ıÂȘ ÁÈ· ÙË ‰È·›ÛÙˆÛË ·ÚÈıÌËÙÈÎÒÓ Î·È ‰ÔÌÈÎÒÓ ¯ÚˆÌÔÛˆÌÈÎÒÓ ·ÓˆÌ·ÏÈÒÓ. ∆· Â˘Ú‹Ì·Ù· Ô˘ ÚÔ·ÙÔ˘Ó ·fi ÙÔÓ ÂÚÁ·ÛÙËÚÈ·Îfi ¤ÏÂÁ¯Ô Ì ÙȘ ·Ú·¿Óˆ Ù¯ÓÈΤ˜ ‚ÔËıÔ‡Ó ÛËÌ·ÓÙÈο ÛÙË ‰È¿ÁÓˆÛË, ÛÙÔÓ Î·ıÔÚÈÛÌfi Ù˘ ÚfiÁÓˆÛ˘ ÙˆÓ ·È‰ÈÒÓ Ì √§§, ÛÙËÓ ÂÈÏÔÁ‹ Ù˘ ηٿÏÏËÏ˘ ıÂÚ·›·˜ Ì ÙËÓ Î·Ï‡ÙÂÚË ‰˘Ó·Ù‹ ¤Î‚·ÛË Î·È ÙȘ ÏÈÁfiÙÂÚ˜ ·ÚÂÓ¤ÚÁÂȘ Î·È ÛÙËÓ ·Ú·ÎÔÏÔ‡ıËÛË ÙˆÓ ·ÛıÂÓÒÓ ÁÈ· ÙËÓ ·Ó›¯Ó¢ÛË ˘ÔÏÂÈfiÌÂÓ˘ ÓfiÛÔ˘.

1 ∂ÚÁ·ÛÙ‹ÚÈÔ π·ÙÚÈ΋˜ °ÂÓÂÙÈ΋˜ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·”, ∞ı‹Ó· 2 ∆Ì‹Ì· ∞ÓÔÛÔÏÔÁ›·˜πÛÙÔÛ˘Ì‚·ÙfiÙËÙ·˜, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·”, ∞ı‹Ó· AÏÏËÏÔÁÚ·Ê›·: ∞ÚÈ¿‰ÓË ª·‡ÚÔ˘ ariamav@hol.gr ∂ÚÁ·ÛÙ‹ÚÈÔ π·ÙÚÈ΋˜ °ÂÓÂÙÈ΋˜ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·” £Ë‚ÒÓ Î·È §Â‚·‰Â›·˜, T.K. 115 27, ∞ı‹Ó·

§¤ÍÂȘ ÎÏÂȉȿ: √§§ ·È‰È΋˜ ËÏÈΛ·˜, ÔÁÎÔÁÔÓ›‰È·, ¯ÚˆÌÔÛˆÌÈΤ˜ ·ÓˆÌ·Ï›Â˜.

Genetic studies in childhood acute lymphoblastic leukaemia F. Tzifi1, A. Kolialexi1, K. Salavoura2, S. Kitsiou1, A. Mavrou1 Abstract: Research in the field of cancer genetics has given rise to a plethora of studies, which indicate that cancer is a genetic disorder of the somatic cells. The classification of childhood haematological malignancies combines cytologic, immunologic and cytogenetic characteristic features. Mutations of proto-oncogenes or tumour-suppressor genes play an important role in the pathogenesis of leukaemias. The application of molecular cytogenetics offers new potential for the laboratory investigation of haematological malignancies in children, through the identification of numerical or structural chromosomal abnormalities, which can determine the diagnosis, prognosis and treatment of the disease. Acute lymphoblastic leukaemia (ALL) is the most common leukaemia in childhood. In this review the molecular, chromosomal and immunophenotypic features of ALL in childhood are reported, which facilitate comprehension of the biology of ALL and its clinical evaluation and treatment.

Key words: ALL, children, oncogenes, chromosome abnormalities.

∂ÈÛ·ÁˆÁ‹ √È ·ÈÌ·ÙÔÏÔÁÈΤ˜ ηÎÔ‹ıÂȘ Â›Ó·È ÔÈ Û˘¯ÓfiÙÂÚÔÈ Î·ÚΛÓÔÈ Ù˘ ·È‰È΋˜ ËÏÈΛ·˜, ·ÓÙÈÚÔÛˆ‡ÔÓÙ·˜ ÙÔ 35-40% ÙˆÓ ·È‰ÈÎÒÓ Î·ÎÔËıÂÈÒÓ. ∏ ÔÍ›· ÏÂÌÊÔ‚Ï·ÛÙÈ΋ Ï¢¯·ÈÌ›· (√§§) ·ÔÙÂÏ› ÙÔ 75% ÙˆÓ Ï¢¯·ÈÌÈÒÓ Ù˘ ·È‰È΋˜ ËÏÈΛ·˜ Î·È ÂÌÊ·Ó›˙ÂÙ·È Î˘Ú›ˆ˜ Û ·È‰È¿ ËÏÈΛ·˜ 3-4 ÂÙÒÓ, Ì ˘ÂÚÔ¯‹ ÙˆÓ ·ÁÔÚÈÒÓ Û ۯ¤ÛË Ì ٷ ÎÔÚ›ÙÛÈ·. ™ÙËÓ ·ÈÙÈÔ·ıÔÁ¤ÓÂÈ· Ù˘ ÓfiÛÔ˘ ÂÓ¤¯ÔÓÙ·È ÁÂÓÂÙÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÙˆÓ ·ÈÌÔÔÈËÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ, ÔÈ Ôԛ˜ Ô‰ËÁÔ‡Ó Û ÔÏÏ·Ï·ÛÈ·ÛÌfi ÙÔ˘ ÎÏÒÓÔ˘. ∆· ΢ÚÈfiÙÂÚ· Û˘ÌÙÒÌ·Ù· Ù˘ √§§ Â›Ó·È ˘ÚÂÙfi˜, ‡ÎÔÏË ÎfiˆÛË, ·ÒÏÂÈ· ‚¿ÚÔ˘˜,

1 Laboratory of Medical Genetics, University of Athens, “Aghia Sophia” Children’s Hospital, Athens, Greece 2 Department of Immunology and Histocompatibility, “Aghia Sophia” Children’s Hospital, Athens, Greece Correspondence: Ariadni Mavrou ariamav@hol.gr Laboratory of Medical Genetics, University of Athens, “Aghia Sophia” Children’s Hospital Thivon & Levadias St., 115 27, Athens, Greece

Ë·ÙÔÌÂÁ·Ï›·, ÏÂÌÊ·‰ÂÓÔ¿ıÂÈ·, Âί˘ÌÒÛÂȘ ‹ ·ÈÌÔÚÚ·Á›Â˜ Î·È Û·ÓÈfiÙÂÚ· ·ÚıÚ›Ùȉ· ‹ Û˘ÌÙÒÌ·Ù· ·fi ÙÔ ÎÂÓÙÚÈÎfi Ó¢ÚÈÎfi Û‡ÛÙËÌ· (∫¡™) (1). ∏ √§§ ηٷٿÛÛÂÙ·È Û 3 ˘ÔÙ‡Ô˘˜ (L1, L2 Î·È L3) Ì ‚¿ÛË ÙÔ Û‡ÛÙËÌ· FAB (FrenchAmerican-British), ÙÔ ÔÔ›Ô ÛÙËÚ›˙ÂÙ·È Û ÌÔÚÊÔÏÔÁÈΤ˜ Î·È Î˘ÙÙ·ÚÔ¯ËÌÈΤ˜ ·Ú·Ì¤ÙÚÔ˘˜ ÙˆÓ ÏÂÌÊÔ‚Ï·ÛÙÒÓ ÙÔ˘ Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ (2,3). √ ·ÓÔÛÔÊ·ÈÓÔÙ˘ÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÚÔÛ‰ÈÔÚ›˙ÂÈ ÙÔÓ Ù‡Ô Ù˘ ΢ÙÙ·ÚÈ΋˜ ÛÂÈÚ¿˜, ·fi ÙËÓ ÔÔ›· ÚÔ¤Ú¯ÂÙ·È Ô Ï¢¯·ÈÌÈÎfi˜ ÎÏÒÓÔ˜ (∆ ‹ µ ÛÂÈÚ¿), ÙÔ ‚·ıÌfi ˆÚÈÌfiÙËÙ·˜ ÙˆÓ Ï¢¯·ÈÌÈÎÒÓ Î˘ÙÙ¿ÚˆÓ Î·È ÙËÓ ÂÙÂÚÔÁ¤ÓÂÈ· ÙÔ˘ ÓÂÔÏ·ÛÌ·ÙÈÎÔ‡ ¶·È‰È·ÙÚÈ΋ 2008;71:255-262

Pediatri Jul-Aug 08

30-07-08

15:52

™ÂÏ›‰·256

256

º. ∆˙ÈÊ‹ Î·È Û˘Ó.

¶›Ó·Î·˜ 1. ∫˘ÙÙ·ÚÔÁÂÓÂÙÈΤ˜ ·ÓˆÌ·Ï›Â˜ Ù˘ µ-√§§, ·ÓÔÛÔÊ·ÈÓÔÙ˘Èο Â˘Ú‹Ì·Ù·, Û˘¯ÓfiÙËÙ· Î·È ÚfiÁÓˆÛË Ô˘ ·Ú·ÙËÚÔ‡ÓÙ·È Û ·˘Ù¤˜ (ÚÔÛ·ÚÌÔÁ‹ ·fi Jonhansson B, et al. Annals of Med 2004) ∫˘ÙÙ·ÚÔÁÂÓÂÙÈο Â˘Ú‹Ì·Ù·

°ÔÓ›‰È·

ÀÔ‰ÈÏÔÂȉ›· <35 ¯ÚˆÌÔÛÒÌ·Ù· 35-44 ¯ÚˆÌÔÛÒÌ·Ù· ÀÂÚ‰ÈÏÔÂȉ›· (>50) t(12;21)(p13;q22)

TEL/AML1

t(1;19)(q23;p13)

∂2∞/PBX1

t(4;11)(q21;q23)

MLL/MLLT2

t(11;19)(q23;p13)

MLL/MLLT1

t(8;14)(q24;q32)

MYC/IGH

∞ÓÔÛÔÊ·ÈÓfiÙ˘Ô˜

™˘¯ÓfiÙËÙ·

¶ÚfiÁÓˆÛË

cIg-, CD10+, CD19+ cIg-, CD10+, CD19+ cIg-, CD10+, CD19+, CD45CD9±, CD10+, CD13+, CD19+, CD20±, CD24+, CD33+, CD34+, CD45cIg+, CD9+, CD10+, CD19+, CD20±, CD22+, CD34CD9+, CD10-, CD15+, CD19+, CD24±, CD33+ CD34+, CD65+ CD10-, CD13±, CD15±, CD19+, CD24+, CD33±, CD34± B ·ÙÙ·ÚÔ Ì sIg

<1% 6% 23-26% 25-30%

∫·Î‹ ∫·Î‹ ∂˘ÓÔ˚΋ ∂˘ÓÔ˚΋

ÎÏÒÓÔ˘. ∆· Â˘Ú‹Ì·Ù· ·˘Ù¿ Û˘Ì‚¿ÏÏÔ˘Ó ÛÙË ‰È¿ÁÓˆÛË, ÙË ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË Ù˘ ÓfiÛÔ˘, ÙËÓ ·Ú·ÎÔÏÔ‡ıËÛË ÙˆÓ ·È‰ÈÒÓ Ì √§§ Î·È ÙËÓ ·Ó›¯Ó¢ÛË Ù˘ ˘ÔÏÂÈfiÌÂÓ˘ ÓfiÛÔ˘ (minimal residual disease) (4,5,6). ∆Ô 85% ÙˆÓ ÂÚÈÙÒÛÂˆÓ √§§ ÚÔ¤Ú¯ÔÓÙ·È ·fi ÙË µ-ÏÂÌÊÔ΢ÙÙ·ÚÈ΋ ÛÂÈÚ¿ Î·È Ù·ÍÈÓÔÌÔ‡ÓÙ·È Û ˘ÔÔÌ¿‰Â˜ ·Ó¿ÏÔÁ· Ì ÙÔ ‚·ıÌfi ˆÚ›Ì·ÓÛ˘ ÙÔ˘ µ ΢ÙÙ¿ÚÔ˘. √ ·ıÔÏÔÁÈÎfi˜ ÎÏÒÓÔ˜ ÂÎÊÚ¿˙ÂÈ Ù· ÂȉÈο ·ÓÙÈÁfiÓ· Ù˘ µ-ÛÂÈÚ¿˜ (CD10, CD19, cCD22, CD20, CD79∞, Tdt) Ì ٷ˘Ùfi¯ÚÔÓË ·ÛıÂÓ‹ ¤ÎÊÚ·ÛË ÙÔ˘ CD45. ∞Ó¿ÏÔÁ· Ì ÙËÓ ¤ÎÊÚ·ÛË ÙˆÓ ·Ú·¿Óˆ ‰ÂÈÎÙÒÓ, Ë µ-√§§ ‰È·ÎÚ›ÓÂÙ·È Û 4 ˘ÔÙ‡Ô˘˜: ÙËÓ ÚÔÚÔ-µ √§§ (µπ), ÙËÓ ÎÔÈÓ‹ √§§ (µππ), ÙËÓ ÚÔ-µ √§§ (µπππ) Î·È ÙËÓ ÒÚÈÌË µ-√§§ (µπV) (¶›Ó·Î·˜ 1). ∏ µππ √§§ ·ÊÔÚ¿ ÙÔ 70% ÙˆÓ ÂÚÈÙÒÛÂˆÓ Î·È ÂÎÊÚ¿˙ÂÈ ÙÔ ‰Â›ÎÙË CD10. √È ·ÛıÂÓ›˜ ¤¯Ô˘Ó ·˘ÍË̤ÓÔ ·ÚÈıÌfi Ï¢ÎÔ΢ÙÙ¿ÚˆÓ ÛÙÔ ÂÚÈÊÂÚÈÎfi ·›Ì· Î·È ·˘ÍË̤ÓË Á·Ï·ÎÙÈ΋ ‰Â¸‰ÚÔÁÂÓ¿ÛË (LDH) (7,8,9). ∏ √§§ ∆-ÏÂÌÊÔ΢ÙÙ·ÚÈ΋˜ ÛÂÈÚ¿˜ ¯·Ú·ÎÙËÚ›˙ÂÙ·È Î˘Ú›ˆ˜ ·fi ÙÔ Î˘ÙÙ·ÚÔÏ·ÛÌ·ÙÈÎfi ·ÓÙÈÁfiÓÔ CD3 (cCD3) Î·È Ù· ·ÓÙÈÁfiÓ· ÂÈÊ·Ó›·˜ CD7, CD5 Î·È CD2. ªÂ ‚¿ÛË ÙÔ˘˜ ‰Â›ÎÙ˜ Ô˘ ηıÔÚ›˙Ô˘Ó ÙÔ ‚·ıÌfi ˆÚ›Ì·ÓÛ˘ ÙÔ˘ ∆ ΢ÙÙ¿ÚÔ˘, Ë √§§ Ù·ÍÈÓÔÌÂ›Ù·È Û 3 ˘ÔÙ‡Ô˘˜: ÚÒÈÌË ∆-√§§ (TdT+, CD7+, cCD3+, CD2±, CD5±, ÂÈÊ·ÓÂÈ·Îfi CD3-, CD4-, CD8-), ÂӉȿÌÂÛË (TdT+, cCD3+, CD2+, CD5+, CD7+, ÂÈÊ·ÓÂÈ·Îfi CD3-, CD4+, CD8+, CD1a+) Î·È ÒÚÈÌË (TdT±, ÂÈÊ·ÓÂÈ·Îfi CD3+, CD2+, CD5+, CD7+, CD1a-, ›Ù CD4+ ›Ù CD8+) (¶›Ó·Î·˜ 2). ∆· ·È‰È¿ Ì ÒÚÈÌË ∆-√§§ ¤¯Ô˘Ó ηχÙÂÚË ÚfiÁÓˆÛË Û˘ÁÎÚÈÙÈο Ì ÙȘ ¿ÏϘ ÌÔÚʤ˜ ∆-√§§ (7,8,9).

∫˘ÙÙ·ÚÔÁÂÓÂÙÈο Î·È ÌÔÚȷο ¯·Ú·ÎÙËÚÈÛÙÈο ÃÚˆÌÔÛˆÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ ·Ó¢ڛÛÎÔÓÙ·È Û ÔPaediatriki 2008;71:255-262

4-5%

∂˘ÓÔ˚΋ Ì ÂÌ̤ÓÔ˘Û· ıÂÚ·›· 2% Û ·È‰È¿ ∫·Î‹ ȉ›ˆ˜ 70-80% Û ‚Ú¤ÊË Û ‚Ú¤ÊË <1% ∫·Î‹ 11% Û ‚Ú¤ÊË 1-5% ∫·Î‹

ÛÔÛÙfi 60-70% ÙˆÓ ·È‰ÈÒÓ Ì √§§ Î·È Û¯ÂÙ›˙ÔÓÙ·È ¿ÌÂÛ· Ì ÙË ‰È¿ÁÓˆÛË, ÙËÓ ÚfiÁÓˆÛË Î·È ÙË ıÂÚ·›· Ù˘ ÓfiÛÔ˘. ¢È·ÎÚ›ÓÔÓÙ·È Û ÚˆÙÔÁÂÓ›˜, Ô˘ ¤¯Ô˘Ó ¿ÌÂÛË Û¯¤ÛË Ì ÙËÓ Î·ÚÎÈÓÔÁ¤ÓÂÛË, Î·È Û ‰Â˘ÙÂÚÔÁÂÓ›˜, Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙËÓ ÂͤÏÈÍË Ù˘ ÓfiÛÔ˘. √È ·ÓˆÌ·Ï›Â˜ ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ÌÔÚ› Ó· Â›Ó·È ·ÚÈıÌËÙÈΤ˜, ‰ÔÌÈΤ˜ ‹ Û˘Ó‰˘·ÛÌfi˜ Î·È ÙˆÓ ‰‡Ô Î·È Û˘Ó‹ıˆ˜ ¤¯Ô˘Ó ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ˘ÂÚ¤ÎÊÚ·ÛË ‹ ·Ó·ÛÙÔÏ‹ Ù˘ ¤ÎÊÚ·Û˘ ÔÁÎÔÁÔÓȉ›ˆÓ, Ù· ÔÔ›· ÂÌϤÎÔÓÙ·È ÛÙËÓ ·ÈÙÈÔ·ıÔÁ¤ÓÂÈ· Î·È ÂͤÏÈÍË Ù˘ ÓfiÛÔ˘ (10). ∞ÚÈıÌËÙÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ √È ·ÚÈıÌËÙÈΤ˜ ¯ÚˆÌÔÛˆÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ Ô‰ËÁÔ‡Ó Û ·‡ÍËÛË ‹ ÂÏ¿ÙÙˆÛË ÙÔ˘ ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡. ∏ ÂÏ¿ÙÙˆÛË ÚÔ·ÙÂÈ ·fi ÌË ÈÛÔ˙˘ÁÈṲ̂Ó˜ ÌÂÙ·ı¤ÛÂȘ, ÂÏÏ›ÌÌ·Ù· ‹ Î·È ·Ô˘Û›· ÔÏfiÎÏËÚˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ (10). ™ÙËÓ ÙÂÏÂ˘Ù·›· ÂÚ›ÙˆÛË, Ë ·Ó›¯Ó¢ÛË ÌÔÓÔۈ̛·˜ ·ÔÙÂÏ› ‰˘ÛÌÂÓ‹ ÚÔÁÓˆÛÙÈÎfi ·Ú¿ÁÔÓÙ·, ÏfiÁˆ Èı·Ó‹˜ ·ÒÏÂÈ·˜ ÔÁÎÔηٷÛÙ·ÏÙÈÎÒÓ ÁÔÓȉ›ˆÓ (11). ∞ÚÈıÌËÙÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ÚÔ·ÙÔ˘Ó Î·È ·fi ·‡ÍËÛË ÁÂÓÂÙÈÎÔ‡ ˘ÏÈÎÔ‡, ÏfiÁˆ ÌÂÚÈ΋˜ ‹ ÔÏÈ΋˜ ÙÚÈۈ̛·˜ ‹ ÔÏ˘ÛˆÌ›·˜. √È ÙÚÈۈ̛˜ ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ 4 Î·È 10 ··ÓÙÒÓÙ·È Û˘¯ÓfiÙÂÚ· ÛÙËÓ √§§ Î·È ¤¯Ô˘Ó ηϋ ÚfiÁÓˆÛË (12). ∏ ˘ÂÚ‰ÈÏÔÂȉ›· (56-67 ¯ÚˆÌÔÛÒÌ·Ù·) ‹ ˘Ô‰ÈÏÔÂȉ›· (35-44 ¯ÚˆÌÔÛÒÌ·Ù·) ·ÔÙÂÏÔ‡Ó ÙȘ Û˘¯ÓfiÙÂÚ· ·ÓȯÓ¢fiÌÂÓ˜ ·ÚÈıÌËÙÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ÛÙËÓ √§§ Ù˘ ·È‰È΋˜ ËÏÈΛ·˜ Î·È ·Ó¢ڛÛÎÔÓÙ·È ÛÙÔ˘˜ L1 Î·È L2 ˘ÔÙ‡Ô˘˜, ÂÓÒ Ô L3 Û˘Ó‰˘¿˙ÂÙ·È Û˘Ó‹ıˆ˜ Ì „¢‰Ô‰ÈÏÔÂȉ›·, ‰ËÏ·‰‹ ‡·ÚÍË 46 ¯ÚˆÌÔۈ̿وÓ, ·ÏÏ¿ Ì ٷ˘Ùfi¯ÚÔÓË ÂÓfi˜ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ Î·È ÂÚ›ÛÛÂÈ· ÂÓfi˜ ¿ÏÏÔ˘. ∆· ¯ÚˆÌÔÛÒÌ·Ù· Ô˘ Û˘Ó‹ıˆ˜ ‰ÈÏ·ÛÈ¿˙ÔÓÙ·È Â›Ó·È

Pediatri Jul-Aug 08

30-07-08

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257

°ÂÓÂÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÔÍ›·˜ ÏÂÌÊÔ‚Ï·ÛÙÈ΋˜ Ï¢¯·ÈÌ›·˜

¶›Ó·Î·˜ 2. √È Î˘ÚÈfiÙÂÚ˜ ΢ÙÙ·ÚÔÁÂÓÂÙÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÛÙËÓ ·È‰È΋ ∆-√§§ Ì ٷ ·ÓÔÛÔÊ·ÈÓÔÙ˘Èο ÙÔ˘˜ Â˘Ú‹Ì·Ù· Î·È ÚfiÁÓˆÛË ·˘ÙÒÓ (ÚÔÛ·ÚÌÔÁ‹ ·fi Jonhansson B, et al. Annals of Med 2004) ∫˘ÙÙ·ÚÔÁÂÓÂÙÈο Â˘Ú‹Ì·Ù·

°ÔÓ›‰È·

∞ÓÔÛÔÊ·ÈÓfiÙ˘Ô˜

™˘¯ÓfiÙËÙ·

¶ÚfiÁÓˆÛË

t(5;14)(q35q32)

BCL11B/HOX11L2

20%

∫·Î‹

t(10;14)(q24q11)

TCR‰/HOX11

4-7%

∂˘ÓÔ˚΋

t(11;14)(p13q11)

TCR‰/LMO1

7%

∫·Î‹

∞Ó·‰È·Ù¿ÍÂȘ TAL1: t(1;14)(p32;q11)

TCR‰/TAL1

3%

∂˘ÓÔ˚΋

t(8;14)(q24q11)

TCR·/MYC

CD1a+, CD2+, cCD3+, CD4±, CD5+, CD7+, CD8±, CD10±, CD34± CD1+, CD2+, CD3+, CD4+, CD5+, CD7+, CD8+, CD10± CD2+, CD3±, CD4+, CD5+, CD7+, CD8+, CD10CD1a±, CD2+, CD3±, CD4±, CD5+, CD7+, CD8±, CD10-, CD15±, CD38+, CD71± CD2+, CD7+, CD3+

1,5%

∫·Î‹

Ù· Ã, 4, 6, 10, 14, 17, 18, 21. ∏ ˘ÂÚÏÔÂȉ›·, Û˘Ó‰˘¿˙ÂÙ·È Ì ¯·ÌËÏfi ·ÚÈıÌfi Ï¢ÎÔ΢ÙÙ¿ÚˆÓ, ·ÓÔÛÔÊ·ÈÓfiÙ˘Ô ÎÔÈÓ‹˜ √§§ Î·È ËÏÈΛ· ÂÌÊ¿ÓÈÛ˘ 1-9 ÂÙÒÓ (13). ∆· ·È‰È¿ Ì ˘ÂÚÏÔÂȉ›· ¤¯Ô˘Ó ηχÙÂÚË ÚfiÁÓˆÛË ·fi ÂΛӷ Ì ˘Ô‰ÈÏÔÂȉ›· (14). ¢ÔÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ √È ‰ÔÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÛÙËÓ √§§ Â›Ó·È ÌÂÙ·ı¤ÛÂȘ ÌÂٷ͇ ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ‹ ÂÏÏ›ÌÌ·Ù·. À¿Ú¯Ô˘Ó 2 ÌÔÚÈ·ÎÔ› Ì˯·ÓÈÛÌÔ›, Ì ÙÔ˘˜ ÔÔ›Ô˘˜ ÔÈ ¯ÚˆÌÔÛˆÌÈΤ˜ ÌÂÙ·ı¤ÛÂȘ Ô‰ËÁÔ‡Ó ÛÙËÓ ·Ó¿Ù˘ÍË ·ÈÌ·ÙÔÏÔÁÈÎÒÓ Î·ÎÔËıÂÈÒÓ. √ ÚÒÙÔ˜ ·ÊÔÚ¿ ÙȘ ıÚ·‡ÛÂȘ ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ Û ı¤ÛÂȘ ÂÓÙfi˜ ÙˆÓ ÁÔÓȉ›ˆÓ (Û˘Ó‹ıˆ˜ Û ÈÓÙÚfiÓÈ·), ÔfiÙÂ Â¿Ó ÙÔ Ï·›ÛÈÔ ·Ó¿ÁÓˆÛ˘ ‰È·ÙËÚ›ٷÈ, ‰ËÌÈÔ˘ÚÁÔ‡ÓÙ·È ¯ÈÌ·ÈÚÈο ÁÔÓ›‰È· Ì ‰È·ÊÔÚÂÙÈ΋ ÏÂÈÙÔ˘ÚÁ›· ·fi ÂΛÓË ÙˆÓ Ê˘ÛÈÔÏÔÁÈÎÒÓ. ªÂ ÙÔ ‰Â‡ÙÂÚÔ Ì˯·ÓÈÛÌfi, Ë ¯ÚˆÌÔÛˆÌÈ΋ ıÚ·‡ÛË Ú·ÁÌ·ÙÔÔÈÂ›Ù·È Û ·Ú·Î›ÌÂÓ˜ ÚˆÙÔÔÁÎÔÁÔÓȉ›ˆÓ ı¤ÛÂȘ, Ì ·ÔÙ¤ÏÂÛÌ· ÙË ‰È·Ù·Ú·¯‹ ¤ÎÊÚ·Û‹˜ ÙÔ˘˜. ∂ÈϤÔÓ, ÛÙȘ ¯ÚˆÌÔÛˆÌÈΤ˜ ÌÂÙ·ı¤ÛÂȘ ¤Ó· ·fi Ù· ÙÌ‹Ì·Ù· Ô˘ ÌÂÙ·Ù›ıÂÙ·È ·ÊÔÚ¿ οÔÈÔ ÌÂÙ·ÁÚ·ÊÈÎfi ·Ú¿ÁÔÓÙ·. √È ÌÂÙ·ÁÚ·ÊÈÎÔ› ·Ú¿ÁÔÓÙ˜ Â›Ó·È Ôχ ÛËÌ·ÓÙÈÎÔ› ÁÈ· ÙËÓ ·Ó¿Ù˘ÍË Î·È ˆÚ›Ì·ÓÛË ÙˆÓ ·ÈÌÔÔÈËÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ. ∂Ô̤ӈ˜, ‰È·Ù·Ú·¯‹ Ù˘ ÏÂÈÙÔ˘ÚÁ›·˜ ÙÔ˘˜ Ô‰ËÁ› Û ·Ó·ÛÙÔÏ‹ ‰È·ÊÔÚÔÔ›ËÛ˘ ÙˆÓ Î˘ÙÙ¿ÚˆÓ, ÂÓÒ ÂÈÚfiÛıÂÙ˜ ÌÂÙ·ÏÏ¿ÍÂȘ ¤¯Ô˘Ó ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙÔÓ Î·ÎÔ‹ıË ÌÂÙ·Û¯ËÌ·ÙÈÛÌfi ÙÔ˘˜ (15). ÃÚˆÌÔÛˆÌÈΤ˜ ÌÂÙ·ı¤ÛÂȘ ÛÙË µ-√§§ ∏ ÈÔ Û˘¯Ó‹ ÌÂÙ¿ıÂÛË Ô˘ ÂÌÊ·Ó›˙ÂÙ·È ÌÂ Û˘¯ÓfiÙËÙ· 25-30% Û ·È‰È¿ Ì µ-√§§, ΢ڛˆ˜ ÛÙËÓ ËÏÈΛ· ÙˆÓ 3-6 ÂÙÒÓ, Â›Ó·È Ë t(12;21)(p13;q22), ηٿ ÙËÓ ÔÔ›· ÙÔ ÁÔÓ›‰ÈÔ TEL ‹ ETV6, Ô˘ Ú˘ıÌ›˙ÂÈ ÙËÓ ·Ú·ÁˆÁ‹ ÌÂÙ·ÁÚ·ÊÈÎÔ‡ ·Ú¿ÁÔÓÙ·, ÌÂÙ·Ù›ıÂÙ·È ·fi Ù· ‚Ú·¯¤· ÛΤÏË ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 12 (p13) ‰›Ï· ÛÙÔ ÁÔÓ›‰ÈÔ AML1(CBFA) ÛÙÔ ¯ÚˆÌfiۈ̷ 21

(21q22) (16). ∏ ¯ÈÌ·ÈÚÈ΋ ÚˆÙ½ÓË Ô˘ ·Ú¿ÁÂÙ·È ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·Ó·‰fiÌËÛË ÙˆÓ ÂÓ˙‡ÌˆÓ ·Ô·ÎÂÙ˘Ï›ˆÛ˘ ÈÛÙÔÓÒÓ Î·È Ô‰ËÁ› ÛÙÔ Û¯ËÌ·ÙÈÛÌfi ÎÏÂÈÛÙ‹˜ ‰ÔÌ‹˜ ¯ÚˆÌ·Ù›Ó˘, Ë ÔÔ›· ÂÌÔ‰›˙ÂÈ ÙË ‰È·‰Èηۛ· ÌÂÙ·ÁÚ·Ê‹˜ (17). ∏ ÌÂÙ¿ıÂÛË ·˘Ù‹ Û˘Ó‰¤ÂÙ·È Ì ·ÓÔÛÔÊ·ÈÓfiÙ˘Ô µππ-√§§ Ì ÂÈϤÔÓ ¤ÎÊÚ·ÛË ÙˆÓ ·ÓÙÈÁfiÓˆÓ CD33 Î·È CD13, ‰ÈÎfiÚ˘ÊË ¤ÎÊÚ·ÛË ÙÔ˘ CD34 Î·È ¯·ÌËÏ‹ ‹ ·Ô‡Û· ¤ÎÊÚ·ÛË ÙÔ˘ CD45 (¶›Ó·Î·˜ 1). ∏ ÌÂÙ¿ıÂÛË ·˘Ù‹ Û¯ÂÙ›˙ÂÙ·È Ì ηϋ ÚfiÁÓˆÛË (18,19). ∆· ‚Ú·¯¤· ÛΤÏË ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 19 (p13) Û˘ÌÌÂÙ¤¯Ô˘Ó Ì ‰‡Ô ÌÂÙ·ı¤ÛÂȘ, ÙËÓ t(1;19)(q23;p13) Î·È ÈÔ Û¿ÓÈ· ÙËÓ t(17;19)(q21;p13), ÔÈ Ôԛ˜ ·Ú·ÙËÚÔ‡ÓÙ·È ÛÙÔ 4-5% ÙˆÓ ·È‰ÈÒÓ Ì √§§. ∏ ÌÂÙ¿ıÂÛË t(1;19)(q23;p13) Ô‰ËÁ› ÛÙË Û‡ÓÙËÍË ÙÔ˘ ÁÔÓȉ›Ô˘ ÙÔ˘ ÌÂÙ·ÁÚ·ÊÈÎÔ‡ ·Ú¿ÁÔÓÙ· ∂2∞ (¯ÚˆÌfiۈ̷ 19p13) Ì ÙÔ ÁÔÓ›‰ÈÔ ƒµÃ1 (¯ÚˆÌfiۈ̷ 1q23). ∆Ô ¯ÈÌ·ÈÚÈÎfi ÁÔÓ›‰ÈÔ ∂2∞/PBX1 Έ‰ÈÎÔÔÈ› ÙËÓ ·Ú·ÁˆÁ‹ ÂÓfi˜ ÌÂÙ·ÁÚ·ÊÈÎÔ‡ ·Ú¿ÁÔÓÙ·, Ô ÔÔ›Ô˜ ·Ó·ÛÙ¤ÏÏÂÈ ÙË ‰È·ÊÔÚÔÔ›ËÛË ÙˆÓ ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ (20). ™Â ÔÛÔÛÙfi 95% Ë ÌÂÙ¿ıÂÛË ·˘Ù‹ Û˘Ó‰˘¿˙ÂÙ·È Ì ˘ÂÚ‰ÈÏÔÂȉ›·. ∆· ·È‰È¿ Ì ·˘Ùfi ÙÔ Î˘ÙÙ·ÚÔÁÂÓÂÙÈÎfi ‡ÚËÌ· ¤¯Ô˘Ó µπππ-√§§ ˘fiÙ˘Ô, ¯·Ú·ÎÙËÚÈÛÙÈ΋ ·ÚÔ˘Û›· ΢ÙÙ·ÚÔÏ·ÛÌ·ÙÈ΋˜ ª ·ÓÔÛÔÛÊ·ÈÚ›Ó˘ (cIgM), ¯·ÌËÏfi ·ÚÈıÌfi Ï¢ÎÔ΢ÙÙ¿ÚˆÓ, ˘„ËÏ‹ ÙÈÌ‹ LDH Î·È Û˘ÌÌÂÙÔ¯‹ ÙÔ˘ ∫¡™ (21). ™ÙË ÌÂÙ¿ıÂÛË t(9;22)(q34;p11) ‹ ¯ÚˆÌfiۈ̷ ºÈÏ·‰¤ÏÊÂÈ·˜ (Ph), ÙÔ 3ã ¿ÎÚÔ ÙÔ˘ ÁÔÓȉ›Ô˘ ABL ·fi ÙÔ ¯ÚˆÌfiۈ̷ 9 ÌÂٷʤÚÂÙ·È ÛÙÔ 5ã ¿ÎÚÔ ÙÔ˘ ÁÔÓȉ›Ô˘ BCR ÛÙÔ ¯ÚˆÌfiۈ̷ 22. ∞˘Ùfi ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙË Á¤ÓÂÛË ¯ÈÌ·ÈÚÈÎÔ‡ mRNA, Ô˘ Ì ÙË ÛÂÈÚ¿ ÙÔ˘ Έ‰ÈÎÔÔÈ› ÌÈ· ¯ÈÌ·ÈÚÈ΋ Ù˘ÚÔÛÈÓÈ΋ ÎÈÓ¿ÛË BCR/ABL Ì ·˘ÍË̤ÓË ‰Ú·ÛÙÈÎfiÙËÙ·. ∞Ó¿ÏÔÁ· Ì ÙÔ ÛËÌÂ›Ô ıÚ·‡Û˘ ÛÙÔ BCR ÁÔÓ›‰ÈÔ, ·Ú¿ÁÔÓÙ·È 2 ·ıÔÏÔÁÈΤ˜ ÔÁÎÔÚˆÙ½Ó˜ Ì ‰È·ÊÔÚÂÙÈÎfi ÌÔÚÈ·Îfi ‚¿ÚÔ˜ Ë Î¿ı ̛·. ™ÙËÓ ·È‰È΋ √§§ ·Ó¢ڛÛÎÂÙ·È Ë ÔÁÎÔÚˆÙ½ÓË p190 BCR/ABL, Û ·ÓÙ›ıÂÛË Ì ¶·È‰È·ÙÚÈ΋ 2008;71:255-262

Pediatri Jul-Aug 08

30-07-08

15:52

™ÂÏ›‰·258

258

º. ∆˙ÈÊ‹ Î·È Û˘Ó.

XÚˆÌfiۈ̷ 8

XÚˆÌfiۈ̷ 14 ™ËÌ›· ıÚ·‡Û˘ 3ã

™ËÌ›· ıÚ·‡Û˘ 5ã

5ã

3ã Vn 1

2

™Ù·ıÂÚ¤˜ ÂÚÈÔ¯¤˜

3

∂ÍfiÓÈ· ÙÔ˘ MYC ÁÔÓȉ›Ô˘

V1

ªÂÙ·‚ÏËÙ¤˜ ÂÚÈÔ¯¤˜

°ÔÓȉȷÎfi˜ ÙfiÔ˜ ‚·ÚÈ¿˜ ·Ï˘Û›‰·˜ ·ÓÔÛÔÛÊ·ÈÚÈÓÒÓ

3ã

5ã

C

V2

C

C

5ã

3ã

2

IGH

3 MYC

ÃÈÌ·ÈÚÈÎfi ÁÔÓ›‰ÈÔ ∂ÈÎfiÓ· 1. ™¯ËÌ·ÙÈ΋ ·ÚÔ˘Û›·ÛË Ù˘ ÌÂÙ¿ıÂÛ˘ ÙÔ˘ ÁÔÓȉ›Ô˘ MYC ÛÙÔ ¯ÚˆÌfiۈ̷ 6 Î·È Ù˘ ‚·ÚÈ¿˜ ·Ï˘Û›‰·˜ ÙˆÓ ·ÓÔÛÔÛÊ·ÈÚÈÓÒÓ ÛÙÔ ¯ÚˆÌfiۈ̷ 14 Û ·ÛıÂÓ›˜ Ì √§§.

ÙË ¯ÚfiÓÈ· Ì˘ÂÏÔÁÂÓ‹ Ï¢¯·ÈÌ›· Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÙËÓ p210 BCR/ABL ÔÁÎÔÚˆÙ½ÓË. ∏ ·Ó›¯Ó¢ÛË ÙÔ˘ ¯ÚˆÌfiۈ̷ÙÔ˜ Ph Â›Ó·È Û¿ÓÈ· ÛÙ· ·È‰È¿ Ì √§§ Î·È ·ÔÙÂÏ› ηÎfi ÚÔÁÓˆÛÙÈÎfi ·Ú¿ÁÔÓÙ· ·ÓÂÍ·Úًو˜ ËÏÈΛ·˜ (22). ÕÏϘ ¯ÚˆÌÔÛˆÌÈΤ˜ ÌÂÙ·ı¤ÛÂȘ Ô˘ ·Ó¢ڛÛÎÔÓÙ·È ÛÙË µ-√§§ Â›Ó·È ·˘Ù¤˜ Ô˘ ·ÊÔÚÔ‡Ó ÙË ¯ÚˆÌÔÛˆÌÈ΋ ı¤ÛË 8q24, ÛÙËÓ ÔÔ›· ÂÓÙÔ›˙ÂÙ·È ÙÔ ÁÔÓ›‰ÈÔ MYC. √È ÌÂÙ·ı¤ÛÂȘ ·˘Ù¤˜ ¤¯Ô˘Ó ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙË ‰È·Ù·Ú·¯‹ Ù˘ ¤ÎÊÚ·Û˘ ÙÔ˘ MYC ÁÔÓȉ›Ô˘, ÏfiÁˆ ·ÌÔÈ‚·›·˜ ÌÂÙ¿ıÂÛ˘ Ì ڢıÌÈÛÙÈο ÛÙÔȯ›· ÙˆÓ ÁÔÓȉ›ˆÓ ÙˆÓ ·ÓÔÛÔÛÊ·ÈÚÈÓÒÓ ÛÙ· ¯ÚˆÌÔÛÒÌ·Ù· 14, 2, Î·È 22 Î·È Â›Ó·È ÔÈ t(8;22)(q24;q11), t(2;8)(p11;q24) Î·È t(8;14)(q24;q32) (∂ÈÎfiÓ· 1). ∞ÔÙ¤ÏÂÛÌ· ÙˆÓ ÌÂÙ·ı¤ÛÂˆÓ ·˘ÙÒÓ Â›Ó·È Ë ˘ÂÚ¤ÎÊÚ·ÛË ÙÔ˘ ÁÔÓȉ›Ô˘ MYC, Ë ÔÔ›· ‰È·ÎfiÙÂÈ ÙË Ê˘ÛÈÔÏÔÁÈ΋ ÔÚ›· ·Ó¿Ù˘Í˘, ‰È·ÊÔÚÔÔ›ËÛ˘ Î·È ·fiÙˆÛ˘ ÙˆÓ ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ. √È ÌÂÙ·ı¤ÛÂȘ ÙÔ˘ MYC ÁÔÓȉ›Ô˘ ·ÊÔÚÔ‡Ó ÏÈÁfiÙÂÚÔ ·fi ÙÔ 5% ÙˆÓ ·È‰ÈÒÓ Ì µπV-√§§ Î·È ÙÔ 1,5% ÙˆÓ ·È‰ÈÒÓ Ì ∆√§§, ÂÓÒ Û˘Ó‹ıˆ˜ ¤¯Ô˘Ó η΋ ÚfiÁÓˆÛË, Ë ÔÔ›· fï˜ ¤¯ÂÈ ‚ÂÏÙȈı› Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· Ì ÙË Û˘Ó‰˘·Ṳ̂ÓË ¯ËÌÂÈÔıÂÚ·›· (23,24). √È ‚ÚÂÊÈΤ˜ Ï¢¯·È̛˜ ·ÔÙÂÏÔ‡Ó ÌÈ· ͯˆÚÈÛÙ‹ ÎÏÈÓÈ΋ ÔÓÙfiÙËÙ· Ì ÌÔÓ·‰Èο ‚ÈÔÏÔÁÈο Î·È ÎÏÈÓÈο ¯·Ú·ÎÙËÚÈÛÙÈο Î·È ÛÙËÓ ÏÂÈÔ„ËÊ›· ·˘ÙÒÓ (80%) ˘¿Ú¯Ô˘Ó ΢ÙÙ·ÚÔÁÂÓÂÙÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 11 ÛÙË Ù·ÈÓ›· q23 Ô˘ Ô‰ËÁ› Û ‰È¿Û·ÛË ÙÔ˘ ÁÔÓȉ›Ô˘ MLL (Mixed Lineage Leukemia). Œ¯Ô˘Ó Paediatriki 2008;71:255-262

ÂÚÈÁÚ·Ê› ¿Óˆ ·fi 30 ‰È·ÊÔÚÂÙÈΤ˜ ÌÂÙ·ı¤ÛÂȘ ÙÔ˘ MLL ÁÔÓȉ›Ô˘, ÙÔ ÔÔ›Ô ·›˙ÂÈ ÚfiÏÔ ÛÙË Ú‡ıÌÈÛË Ù˘ ÌÂÙ·ÁÚ·Ê‹˜. ∏ ÈÔ Û˘¯Ó‹ ÌÂÙ¿ıÂÛË Â›Ó·È Ë t(4;11)(q21;q23), fiÔ˘ Û˘Ó˘¿Ú¯ÂÈ ÔÚÁ·ÓÔÌÂÁ·Ï›·, ˘„ËÏfi˜ ·ÚÈıÌfi˜ Ï¢ÎÔ΢ÙÙ¿ÚˆÓ ÛÙÔ ÂÚÈÊÂÚÈÎfi ·›Ì· Î·È Û˘ÌÌÂÙÔ¯‹ ÙÔ˘ ∫¡™, Ô ‰Â ·ÓÔÛÔÊ·ÈÓfiÙ˘Ô˜ Â›Ó·È Û˘Ó‹ıˆ˜ µπ-√§§ (25,26). ™˘¯Ó¿ ÂÎÊÚ¿˙ÔÓÙ·È Î·È Ù· ·ÓÙÈÁfiÓ· Ì˘ÂÏÈ΋˜ ÛÂÈÚ¿˜, fiˆ˜ Ù· CD13, CD15 Î·È CD33 (20). ∏ ÚfiÁÓˆÛË Ù˘ ÌÂÙ¿ıÂÛ˘ ·˘Ù‹˜ Â›Ó·È ¯ÂÈÚfiÙÂÚË fiÙ·Ó ··ÓÙ¿Ù·È ÛÙȘ ‚ÚÂÊÈΤ˜ Ï¢¯·È̛˜, ÂÓÒ Â›Ó·È Ï›ÁÔ Î·Ï‡ÙÂÚË fiÙ·Ó ·Ó¢ڛÛÎÂÙ·È Û ·È‰È¿ ËÏÈΛ·˜ 1-9 ÂÙÒÓ (20,27). ¶ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ‰Â›¯ÓÔ˘Ó ÂÏ·Ùو̤ÓË ¤ÎÊÚ·ÛË ÙÔ˘ ÔÁÎÔηٷÛÙ·ÏÙÈÎÔ‡ ÁÔÓȉ›Ô˘ FHIT (Fragile Histidine Triad) ÛÙËÓ √§§ Ì ·Ó·‰È¿Ù·ÍË ÙÔ˘ MLL ÁÔÓȉ›Ô˘ Î·È Â›Ó·È Èı·Ófi Ë

∂ÈÎfiÓ· 2. ∆¯ÓÈ΋ FICTION: ∞. ∞ÓÔÛÔÊ·ÈÓÔÙ˘È΋ ¯ÚÒÛË ÓÂÔÏ·ÛÌ·ÙÈÎÔ‡ ΢ÙÙ¿ÚÔ˘ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜ ·fi ·ÛıÂÓ‹ Ì √§§ Ì ÌÔÓÔÎψÓÈÎfi ·Óٛۈ̷ ¤Ó·ÓÙÈ ÙÔ˘ ˘Ô‰Ô¯¤· ÂÈÊ·Ó›·˜ CD34. B. To ›‰ÈÔ Î‡ÙÙ·ÚÔ ‡ÛÙÂÚ· ·fi ÌÂϤÙË Ì FISH Ì ÂȉÈÎfi DNA ·ÓȯÓÂ˘Ù‹ Ù˘ ÌÂÙ¿ıÂÛ˘ BCR/abl.

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°ÂÓÂÙÈÎfi˜ ¤ÏÂÁ¯Ô˜ ÔÍ›·˜ ÏÂÌÊÔ‚Ï·ÛÙÈ΋˜ Ï¢¯·ÈÌ›·˜

ÂÏ¿ÙÙˆÛË ·˘Ù‹ Ó· ·›˙ÂÈ ÚfiÏÔ ÛÙËÓ ·ıÔÁ¤ÓÂÈ· Î·È ÂͤÏÈÍË Ù˘ ÓfiÛÔ˘. ∆Ô ÁÔÓ›‰ÈÔ ·˘Ùfi ‚Ú›ÛÎÂÙ·È ÛÙÔ ¯ÚˆÌfiۈ̷ 3 ÛÙËÓ ÈÔ ÎÔÈÓ‹ ı¤ÛË Â˘ıÚ·˘ÛÙfiÙËÙ·˜ Ô˘ ˘¿Ú¯ÂÈ ÛÙÔ ·ÓıÚÒÈÓÔ ÁÔÓȉ›ˆÌ· Î·È ÂÓ¤¯ÂÙ·È ÛÙËÓ ·ıÔÁ¤ÓÂÈ· ÔÏÏÒÓ ÌÔÚÊÒÓ Î·ÚΛÓÔ˘, Ô ‰Â ÚfiÏÔ˜ ÙÔ˘ ‰ÂÓ ¤¯ÂÈ Ï‹Úˆ˜ ‰È¢ÎÚÈÓÈÛı› (28). ÃÚˆÌÔÛˆÌÈΤ˜ ÌÂÙ·ı¤ÛÂȘ ÛÙËÓ ∆-√§§ ™Â fi,ÙÈ ·ÊÔÚ¿ ÙËÓ ∆-√§§, Û ÔÛÔÛÙfi ÂÚ›Ô˘ 35% ÔÈ ¯ÚˆÌÔÛˆÌÈΤ˜ ÌÂÙ·ı¤ÛÂȘ Û¯ÂÙ›˙ÔÓÙ·È Ì ¤Ó· ·fi Ù· ÁÔÓ›‰È· ÙÔ˘ ˘Ô‰Ô¯¤· ÙˆÓ ∆-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ (TCR - T-cell Receptor), fiˆ˜ ÙÔ ÁÔÓ›‰ÈÔ TCR·‰ Î·È ÙÔ TCR‚ ÛÙ· ¯ÚˆÌÔÛÒÌ·Ù· 14 Î·È 7 ·ÓÙÈÛÙÔ›¯ˆ˜, Ù· ÔÔ›· ÌÂÙ·Ù›ıÂÓÙ·È Û ı¤ÛÂȘ ÁÔÓȉ›ˆÓ Ô˘ Έ‰ÈÎÔÔÈÔ‡Ó ÌÂÙ·ÁÚ·ÊÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜. ∆Ô ·ÔÙ¤ÏÂÛÌ· Â›Ó·È Ë ‰È·Ù·Ú·¯‹ Ù˘ ·Ó¿Ù˘Í˘, ‰È·ÊÔÚÔÔ›ËÛ˘ Î·È ÂÈ‚›ˆÛ˘ ÙˆÓ ∆ ΢ÙÙ¿ÚˆÓ (29,30). √È ÌÂÙ·ÁÚ·ÊÈÎÔ› ·Ú¿ÁÔÓÙ˜ Ô˘ ÂÌϤÎÔÓÙ·È ÛÙËÓ ·ıÔÁ¤ÓÂÛË ÙˆÓ ∆-√§§ Â›Ó·È ÔÈ TAL1, HOX11L2, HOX11, TAL2, BHLHB1, LYL1, LMO1(11p15) Î·È LMO2(11p13). ∏ ÁÔÓȉȷ΋ ¤ÎÊÚ·ÛË ÙˆÓ LYL1 Î·È LMO2 ÛÙ· Ï¢¯·ÈÌÈο ·ÙÙ·Ú· ÌÔÈ¿˙ÂÈ Ì ÂΛÓË ÙˆÓ Î˘ÙÙ¿ÚˆÓ Ô˘ ‚Ú›ÛÎÔÓÙ·È ÛÙÔ ÚÔ-∆ ÛÙ¿‰ÈÔ ·Ó¿Ù˘Í˘ (20). ∏ ÌÂÙ¿ıÂÛË t(5;14)(q35;q32) ··ÓÙ¿Ù·È Û ÔÛÔÛÙfi ÂÚ›Ô˘ 20% ÙˆÓ ·È‰ÈÒÓ Ì ∆-√§§ (¶›Ó·Î·˜ 3), Ë ÚfiÁÓˆÛ‹ Ù˘ Â›Ó·È Î·Î‹ Î·È ÙÔ ·ÔÙ¤ÏÂÛÌ· Ù˘ ÌÂÙ¿ıÂÛ˘ ·˘Ù‹˜ Â›Ó·È Ë ˘ÂÚ¤ÎÊÚ·ÛË ÙÔ˘ ÁÔÓȉ›Ô˘ HOX11L2 Ô˘ Ê˘ÛÈÔÏÔÁÈο ÂÓÙÔ›˙ÂÙ·È ÛÙ· Ì·ÎÚ¿ ÛΤÏË ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 5 (31,32). §ÈÁfiÙÂÚÔ Û˘¯Ó‹ (Û ÔÛÔÛÙfi 4-7%) Â›Ó·È Ë ÌÂÙ¿ıÂÛË t(10;14) Ô˘ ·ÊÔÚ¿ ÙÔ ÁÔÓ›‰ÈÔ HOX11. ÀÂÚ¤ÎÊÚ·ÛË ÙÔ˘ ÁÔÓȉ›Ô˘ HOX11 ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙË ‰È·Ù·Ú·¯‹ ÙÔ˘ ΢ÙÙ·ÚÈÎÔ‡ ·ÎÏÔ˘ ÛÙË Ê¿ÛË G2 Î·È Û¯ÂÙ›˙ÂÙ·È Ì ηϋ ÚfiÁÓˆÛË (33). ∏ ÌÂÙ¿ıÂÛË t(1;14)(p32;q11), ÛÙËÓ ÔÔ›· ÙÔ ÁÔÓ›‰ÈÔ TAL1 (‹ SCL) ·fi ÙË ¯ÚˆÌÔÛˆÌÈ΋ ı¤ÛË 1p33 ÌÂÙ·Ù›ıÂÙ·È ÛÙË ı¤ÛË ÙÔ˘ ÁÔÓȉ›Ô˘ TCR‰ ÛÙÔ ¯ÚˆÌfiۈ̷ 14, ¤¯ÂÈ ˆ˜ ·ÔÙ¤ÏÂÛÌ· ÙËÓ ˘ÂÚ¤ÎÊÚ·ÛË ÙÔ˘ TAL1 Î·È ··ÓÙ¿Ù·È ÛÙÔ 3% ÙˆÓ ·È‰ÈÒÓ Ì ∆√§§ (33,34). ∆Ô ÁÔÓ›‰ÈÔ TAL1 Έ‰ÈÎÔÔÈ› ÙÔÓ ÔÌÒÓ˘ÌÔ ÌÂÙ·ÁÚ·ÊÈÎfi ·Ú¿ÁÔÓÙ·, Ô ÔÔ›Ô˜ ÂÎÊÚ¿˙ÂÙ·È ÛÙ· ÚÔÁÔÓÈο ·ÙÙ·Ú· Ù˘ ·ÈÌÔÔÈËÙÈ΋˜ ÛÂÈÚ¿˜ Î·È Â›Ó·È ··Ú·›ÙËÙÔ˜ ÁÈ· ÙËÓ ·ÈÌÔÔ›ËÛË (35). Œ¯ÂÈ ·Ú·ÙËÚËı› fiÙÈ Ë Ï¢¯·ÈÌÔÁfiÓÔ˜ ‰Ú¿ÛË ÙÔ˘ TAL1 ÔÊ›ÏÂÙ·È Û ·ÏÏËÏÂȉڿÛÂȘ Ì ¿ÏÏÔ˘˜ ·Ú¿ÁÔÓÙ˜ ÌÂÙ·ÁÚ·Ê‹˜, fiˆ˜ Ô ∂12 Î·È Ô ∂47, Î·È fiÙÈ ·ÎfiÌ· Î·È Ë ¤ÏÏÂÈ„‹ ÙÔ˘ ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û ÓÂÔÏ·ÛÌ·ÙÈ΋ ÂÍ·ÏÏ·Á‹ (20). ¶ÈÔ Û¿ÓÈ· Â›Ó·È Ë ÌÂÙ¿ıÂÛË t(4;11)(q21;p15.5), Ë ÔÔ›· Û˘¯Ó¿ Û˘Ó˘¿Ú¯ÂÈ Ì ¤ÏÏÂÈÌÌ· ÛÙ· ‚Ú·¯¤· ÛΤÏË ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 12 (12p) Î·È ¤¯ÂÈ Î·Î‹ ÚfiÁÓˆÛË (36).

™ÙËÓ ·ıÔÁ¤ÓÂÈ· ΢ڛˆ˜ Ù˘ ∆-√§§, ·ÏÏ¿ Î·È Ù˘ µ-√§§, Èı·ÓfiÓ Ó· ·›˙Ô˘Ó ÚfiÏÔ ÎÏËÚÔÓÔÌÔ‡ÌÂÓ˜ ÌÂÙ·ÏÏ¿ÍÂȘ ÙÔ˘ ∞∆ª ÁÔÓȉ›Ô˘, ÔÈ Ôԛ˜ Â›Ó·È Î˘Ú›ˆ˜ ·ÚÂÚÌËÓ‡ÛÈ̘ (37). ∆Ô ÁÔÓ›‰ÈÔ ∞∆ª ÂÓÙÔ›˙ÂÙ·È ÛÙ· Ì·ÎÚ¿ ÛΤÏË ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 11 (11q23) Î·È Îˆ‰ÈÎÔÔÈ› ÌÈ· ʈÛÊÔÚˆÙ½ÓË ÌÂÁ¤ıÔ˘˜ 350 kd Ô˘ ·›˙ÂÈ ÚfiÏÔ ÛÙËÓ ÂȉÈfiÚıˆÛË ÙˆÓ ‚Ï·‚ÒÓ ÙÔ˘ DNA. ªÂÙ·ÏÏ¿ÍÂȘ Î·È ÛÙ· ‰‡Ô ·ÏÏËÏfiÌÔÚÊ· ÙÔ˘ ÁÔÓȉ›Ô˘ Â›Ó·È ˘‡ı˘Ó˜ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ÌÈ·˜ Û¿ÓÈ·˜ ÁÂÓÂÙÈ΋˜ ÓfiÛÔ˘, Ù˘ ·Ù·Í›·˜ÙËÏ·ÁÁÂÈÂÎÙ·Û›·˜ (∞-∆), Ë ÔÔ›· ·Ó‹ÎÂÈ ÛÙ· Û‡Ó‰ÚÔÌ· ÂȉÈfiÚıˆÛ˘. √È ·ÛıÂÓ›˜ Ì ∞-∆ ÂÌÊ·Ó›˙Ô˘Ó Û˘¯Ó¿ ÓÂÔϷۛ˜ Î·È Î˘Ú›ˆ˜ Ï¢¯·È̛˜ Î·È ÏÂÌÊÒÌ·Ù· ÛÙËÓ ·È‰È΋ ËÏÈΛ· (37). ÕÏϘ ‰ÔÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ∂ÎÙfi˜ ·fi ÙȘ ¯ÚˆÌÔÛˆÌÈΤ˜ ÌÂÙ·ı¤ÛÂȘ, Â›Ó·È ‰˘Ó·Ùfi Ó· ˘¿Ú¯Ô˘Ó ÛÙËÓ ·È‰È΋ √§§ Î·È ÂÏÏ›ÌÌ·Ù· ÙˆÓ ¯ÚˆÌÔۈ̿وÓ, ÂÎ ÙˆÓ ÔÔ›ˆÓ Ù· ÈÔ Û˘Ó‹ıË ··ÓÙÒÓÙ·È ÛÙ· ‚Ú·¯¤· ÛΤÏË ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ 9 Î·È 12 Î·È ÛÙ· Ì·ÎÚ¿ ÛΤÏË ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 6. ¢È·Ù·Ú·¯¤˜ ÛÙ· ‚Ú·¯¤· ÛΤÏË ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 9 (p21) Ô‰ËÁÔ‡Ó ÛÙËÓ ·ÒÏÂÈ· ÏÂÈÙÔ˘ÚÁ›·˜ ÙˆÓ ·Ó·ÛÙÔϤˆÓ ÙˆÓ ÎÈÓ·ÛÒÓ Ô˘ ÂÍ·ÚÙÒÓÙ·È ·fi ÙËÓ Î˘ÎÏ›ÓË (CDK1) (p16INK4a/p14ARF Î·È p15INK4b) Î·È ·Ó¢ڛÛÎÂÙ·È ÛÙÔ 80% ÙˆÓ ·È‰ÈÒÓ Ì ∆-√§§ Î·È ÛÙÔ 20% Ù˘ µ-√§§ (38). ∏ ‰È·Ù·Ú·¯‹ ÛÙËÓ ¤ÎÊÚ·ÛË ÙˆÓ ·ÓˆÙ¤Úˆ ÁÔÓȉ›ˆÓ ÛÙËÓ √§§ ÌÔÚ› Ó· ÚÔ·„ÂÈ ·fi ÂÏÏ›ÌÌ·Ù· Î·È ÛËÌÂȷΤ˜ ÌÂÙ·ÏÏ¿ÍÂȘ, ηıÒ˜ Î·È Ì¤Ûˆ ÂÈÁÂÓÂÙÈÎÒÓ Ì˯·ÓÈÛÌÒÓ, Ô ÚfiÏÔ˜ ÙÔ˘˜ fï˜ ÛÙËÓ ÚfiÁÓˆÛË Ù˘ √§§ Â›Ó·È ·ÌÊ›‚ÔÏÔ˜ (39,40). ∆Ô ¯ÚˆÌfiۈ̷ 9 Û˘ÌÌÂÙ¤¯ÂÈ Û˘¯Ó¿ ÛÙÔ Û¯ËÌ·ÙÈÛÌfi ‰ÈÎÂÓÙÚÈÎÒÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ Ì ٷ ¯ÚˆÌÔÛÒÌ·Ù· 12 Î·È 20, Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·ÒÏÂÈ· ÁÔÓȉ›ˆÓ ÙfiÛÔ ÛÙÔ 9p fiÛÔ Î·È ÛÙÔ 12 ‹ ÛÙÔ 20 (39). ∞ÒÏÂÈ· Ù˘ ÂÙÂÚÔ˙˘ÁˆÙ›·˜ ÛÙÔ ¯ÚˆÌfiۈ̷ 12 ·Ú·ÙËÚÂ›Ù·È ÛÙÔ 17-33% ÙˆÓ ÂÚÈÙÒÛÂˆÓ Ì √§§ Î·È Û¯ÂÙ›˙ÂÙ·È Ì ηϋ ÚfiÁÓˆÛË (41).

∂ÚÁ·ÛÙËÚȷΤ˜ ̤ıÔ‰ÔÈ ÌÂϤÙ˘ ÁÂÓÂÙÈÎÒÓ ·ÓˆÌ·ÏÈÒÓ ÛÙËÓ √§§ √ ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ Ù˘ √§§ ÂÚÈÏ·Ì‚¿ÓÂÈ ÂÚÁ·ÛÙËÚȷΤ˜ Ù¯ÓÈΤ˜ Ô˘ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ‰È·‰Ô¯Èο ÁÈ· ÙË ‰È¿ÁÓˆÛË Î·È Ù·ÍÈÓfiÌËÛË Ù˘ ÓfiÛÔ˘ Û هÔ˘˜ Î·È ˘ÔÙ‡Ô˘˜. ∆Ô ÚÒÙÔ ‚‹Ì· ÁÈ· ÙËÓ Â‡ÚÂÛË ÙÔ˘ ·ıÔÏÔÁÈÎÔ‡ ÎÏÒÓÔ˘ ÂÚÈÏ·Ì‚¿ÓÂÈ ÙË ÌÈÎÚÔÛÎÔÈ΋ ÂͤٷÛË ÙˆÓ ·ÈÌÔÔÈËÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ ÙÔ˘ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜ ‹/Î·È ÙÔ˘ Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ. ŒÙÛÈ Î·ıÔÚ›˙ÔÓÙ·È Ù· ÌÔÚÊÔÏÔÁÈο Î·È Î˘ÙÙ·ÚÔ¯ËÌÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÙˆÓ ÏÂÌÊÔ‚Ï·ÛÙÒÓ ‚¿ÛÂÈ Ù˘ FAB Ù·ÍÈÓfiÌËÛ˘ (42). ∏ ΢ÙÙ·ÚÔÌÂÙÚ›· ÚÔ‹˜ ηıÔÚ›˙ÂÈ ÙÔÓ ·ÓÔÛÔÊ·ÈÓfiÙ˘Ô ÙˆÓ Î˘ÙÙ¿ÚˆÓ ÙÔ˘ ÓÂÔÏ·ÛÌ·ÙÈÎÔ‡ ÎÏÒÓÔ˘ Ì ¶·È‰È·ÙÚÈ΋ 2008;71:255-262

Pediatri Jul-Aug 08

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º. ∆˙ÈÊ‹ Î·È Û˘Ó.

ÙË ¯Ú‹ÛË ÂȉÈÎÒÓ ‰ÂÈÎÙÒÓ ÁÈ· ÙË ÛÂÈÚ¿ ÚÔ¤Ï¢Û˘ (∆ ‹ µ), fiˆ˜ Ô CD19 ÁÈ· ÙË µ-ÛÂÈÚ¿ Î·È Ô CD7 ÁÈ· ÙËÓ ∆-ÛÂÈÚ¿. ªÂ ÙË ¯Ú‹ÛË ¿ÏÏˆÓ ÌÔÓÔÎψÓÈÎÒÓ ·ÓÙÈÛˆÌ¿ÙˆÓ Î·ıÔÚ›˙ÂÙ·È Ô ‚·ıÌfi˜ ˆÚÈÌfiÙËÙ·˜ ÙˆÓ Ï¢¯·ÈÌÈÎÒÓ Î˘ÙÙ¿ÚˆÓ Î·È ÂÈϤÔÓ ·ÓȯÓ‡ÔÓÙ·È ¿Ù˘ÔÈ ‹ ÌË Ê˘ÛÈÔÏÔÁÈÎÔ› Ê·ÈÓfiÙ˘ÔÈ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ˘ÔΛÌÂÓ˜ ÁÂÓÂÙÈΤ˜ ·ÓˆÌ·Ï›Â˜. À¿Ú¯Ô˘Ó ‰È¿ÊÔÚ˜ ÚÔÙ¿ÛÂȘ ÁÈ· Ù· ÌÔÓÔÎψÓÈο ·ÓÙÈÛÒÌ·Ù· Ô˘ ÌÔÚÔ‡Ó Ó· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó Î·Ù¿ ÙÔÓ ¤ÏÂÁ¯Ô ÚÔ˘Ù›Ó·˜ ÁÈ· ÙË ‰È¿ÁÓˆÛË Ù˘ √§§, ·ÏÏ¿ ‰ÂÓ ˘¿Ú¯ÂÈ ÁÂÓÈ΋ ÔÌÔʈӛ·. ™˘Ó‹ıˆ˜, ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ˆ˜ ÁÂÓÈÎÔ› ‰Â›ÎÙ˜ Ù· ·ÓÙÈÁfiÓ· CD39, HLA-DR, CD45 Î·È Tdt, ˆ˜ ‰Â›ÎÙ˜ Ù˘ µ-ÛÂÈÚ¿˜ Ù· CD19, CD10, CD22, CD20 Î·È CD79a Î·È ˆ˜ ‰Â›ÎÙ˜ Ù˘ ∆-ÛÂÈÚ¿˜ Ù· CD1a, CD2, cCD3, CD4, CD8, CD5 Î·È CD7. ∂›Û˘, Ì ÙËÓ Î˘ÙÙ·ÚÔÌÂÙÚ›· ÚÔ‹˜, ÂÎÙfi˜ ·fi ÙÔÓ ÎÏ·ÛÈÎfi ΢ÙÙ·ÚÔÁÂÓÂÙÈÎfi ¤ÏÂÁ¯Ô, Â›Ó·È ‰˘Ó·Ù‹ Ë ·Ó‡ÚÂÛË ·ÚÈıÌËÙÈÎÒÓ ¯ÚˆÌÔÛˆÌÈÎÒÓ ·ÓˆÌ·ÏÈÒÓ, ‰Â‰Ô̤ÓÔ˘ fiÙÈ Ë ¤ÓÙ·ÛË ÙÔ˘ ÊıÔÚÈÛÌÔ‡ οı ¯ÚˆÌÔÛÒÌ·ÙÔ˜ Û¯ÂÙ›˙ÂÙ·È ¿ÌÂÛ· Ì ÙÔ ÁÂÓÂÙÈÎfi ˘ÏÈÎfi Ô˘ ÂÚȤ¯ÂÈ. ªÂ ·˘ÙfiÓ ÙÔÓ ÙÚfiÔ Â›Ó·È ‰˘Ó·Ùfi˜ Ô Î·ıÔÚÈÛÌfi˜ ÙˆÓ ˙¢ÁÒÓ Î¿ı ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ÛÙÔ ˘fi ÌÂϤÙË ÁÂÓÂÙÈÎfi ˘ÏÈÎfi Î·È Ë Ù·˘ÙÔÔ›ËÛË ÌÔÓÔۈ̛·˜ ‹ ÙÚÈۈ̛·˜. ™ÙËÓ Î˘ÙÙ·ÚÔÌÂÙÚ›· ÚÔ‹˜, Ë ÌÔÓÔۈ̛· ÂÓfi˜ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÂÏ¿ÙÙˆÛË Ù˘ ¤ÓÙ·Û˘ ηٿ 50% ÙÔ˘ ÊıÔÚÈÛÌÔ‡, ÂÓÒ Ë ÙÚÈۈ̛· ·fi ·‡ÍËÛË Î·Ù¿ 50% (5,42). √ ΢ÙÙ·ÚÔÁÂÓÂÙÈÎfi˜ Î·È ÌÔÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ Â›Ó·È ·Ó·ÓÙÈηٿÛÙ·ÙÔ˜ ÁÈ· ÙË ‰È¿ÁÓˆÛË Ù˘ √§§, ÙËÓ ÚfiÁÓˆÛË Î·È ÙËÓ ·Ó›¯Ó¢ÛË Ù˘ ˘ÔÏÂÈfiÌÂÓ˘ ÓfiÛÔ˘. √ ηڢfiÙ˘Ô˜ ¯ÚËÛÈÌÔÔÈÂ›Ù·È Â˘Ú¤ˆ˜ ÁÈ· ÙË ‰È·›ÛÙˆÛË ¯ÚˆÌÔÛˆÌÈÎÒÓ ·ÓˆÌ·ÏÈÒÓ ÛÙÔ ÓÂÔÏ·ÛÌ·ÙÈÎfi ÎÏÒÓÔ Î·È ·ÔÙÂÏ› ·ÓÂÍ¿ÚÙËÙÔ ÚÔÁÓˆÛÙÈÎfi ·Ú¿ÁÔÓÙ· ÙˆÓ ·ÈÌ·ÙÔÏÔÁÈÎÒÓ Î·ÎÔËıÂÈÒÓ. °È· ÙË ‰È¿ÁÓˆÛË Ù˘ √§§ Ú¤ÂÈ Ó· ÌÂÏÂÙËıÔ‡Ó ÙÔ˘Ï¿¯ÈÛÙÔÓ 20 ÌÂÙ·Ê¿ÛÂȘ ÁÈ· ÙË ‰È¿ÁÓˆÛË Ù˘ √§§ Î·È ÁÈ’ ·˘Ùfi Ô ·ÚÈıÌfi˜ ÙˆÓ Î˘ÙÙ¿ÚˆÓ ÙÔ˘ Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ Ô˘ ··ÈÙÔ‡ÓÙ·È Â›Ó·È ÂÚ›Ô˘ 5x107. ªÂ ·˘Ù‹ ÙËÓ ÎÏ·ÛÈ΋ Ù¯ÓÈ΋ Â›Ó·È ‰˘Ó·Ù‹ Ë Ù·˘ÙÔÔ›ËÛË ·ÚÈıÌËÙÈÎÒÓ Î·È ‰ÔÌÈÎÒÓ ·ÓˆÌ·ÏÈÒÓ ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ÌÂÁ¤ıÔ˘˜ 3-5 Mb DNA Û ΢ÙÙ·ÚÈÎfi Â›‰Ô. ªÂÈÔÓÂÎÙ‹Ì·Ù· Ù˘ ÌÂıfi‰Ô˘ ·ÔÙÂÏÔ‡Ó Ë Û˘¯Ó‹ ·ÔÙ˘¯›· Ù˘ ηÏÏȤÚÁÂÈ·˜ ΢ÙÙ¿ÚˆÓ Ì˘ÂÏÔ‡ ÙˆÓ ÔÛÙÒÓ, Ë Î·Î‹ ÔÈfiÙËÙ· Î·È Ô ÌÈÎÚfi˜ ·ÚÈıÌfi˜ ÙˆÓ ÌÂÙ·Ê¿ÛˆÓ, Ë ·ÚÔ˘Û›· ÔÏÏ·ÏÒÓ ·ıÔÏÔÁÈÎÒÓ ÎÏÒÓˆÓ, ηıÒ˜ Î·È Ë ·‰˘Ó·Ì›· ·Ó›¯Ó¢Û˘ ‰ÔÌÈÎÒÓ ÌÂÙ·‚ÔÏÒÓ ÌÂÁ¤ıÔ˘˜ ÌÈÎÚfiÙÂÚˆÓ ÙˆÓ 3 Mb ‹ Î·È ÂÓÙÔÈ˙fiÌÂÓˆÓ ÛÙ· ÙÂÏÔÌÂÚ›‰È· ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ (42,43). ∂¿Ó ‰ÂÓ Â›Ó·È ‰˘Ó·Ù‹ Ë Ï‹„Ë ‰Â›ÁÌ·ÙÔ˜ ·fi ÙÔ Ì˘ÂÏfi ÙˆÓ ÔÛÙÒÓ, Ë ·Ó›¯Ó¢ÛË ÙˆÓ ¯ÚˆÌÔÛˆÌÈÎÒÓ ·ÓˆÌ·ÏÈÒÓ ÌÔÚ› Ó· Á›ÓÂÈ Î·È Û ‚Ï·ÛÙÈο ·ÙÙ·Ú· ÙÔ˘ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜. ™Â ·˘Ù‹ ÙËÓ ÂÚ›ÙˆÛË Paediatriki 2008;71:255-262

‰ÂÓ ÚÔÛÙ›ıÂÙ·È ÌÈÙÔÁfiÓÔ (Ê˘ÙÔ·ÈÌ·ÙÔÁÏÔ˘ÙÈÓ›ÓË) ÛÙÔ ˘ÏÈÎfi Ù˘ ηÏÏȤÚÁÂÈ·˜, ¤ÙÛÈ ÒÛÙ ӷ ÔÏÏ·Ï·ÛÈ·ÛÙÔ‡Ó ÌfiÓÔ Ù· ÓÂÔÏ·ÛÌ·ÙÈο ·ÙÙ·Ú·. ∏ Ù¯ÓÈ΋ ÙÔ˘ ÊıÔÚ›˙ÔÓÙÔ˜ in situ ˘‚ÚȉÈÛÌÔ‡ (FISH - fluorescent in situ hybridization), Ì ÙË ¯Ú‹ÛË ÂȉÈÎÒÓ DNA ·ÓȯÓ¢ÙÒÓ, ¤¯ÂÈ Û˘Ì‚¿ÏÏÂÈ ÒÛÙ ӷ ÍÂÂÚ·ÛÙÔ‡Ó Ù· ÚÔ‚Ï‹Ì·Ù· Ù˘ ÎÏ·ÛÈ΋˜ ΢ÙÙ·ÚÔÁÂÓÂÙÈ΋˜ ·Ó¿Ï˘Û˘ (43,44). ∏ Ù¯ÓÈ΋ ·˘Ù‹ ¯ÚËÛÈÌÔÔÈÂ›Ù·È Â˘Ú¤ˆ˜ Î·È ÁÈ· ÙË ‰È¿ÁÓˆÛË ˘ÔÏÂÈfiÌÂÓ˘ ÓfiÛÔ˘. ªÂÁ¿ÏÔ ÏÂÔÓ¤ÎÙËÌ· Ù˘ ÌÂıfi‰Ô˘ FISH ·ÔÙÂÏ› Ë ‰˘Ó·ÙfiÙËÙ· ·Ó›¯Ó¢Û˘ ·ÚÈıÌËÙÈÎÒÓ Î·È ‰ÔÌÈÎÒÓ ¯ÚˆÌÔÛˆÌÈÎÒÓ ·ÓˆÌ·ÏÈÒÓ, ·ÎfiÌË Î·È Û ÌÂÛÔÊ·ÛÈÎÔ‡˜ ˘Ú‹Ó˜, ÁÂÁÔÓfi˜ Ô˘ ÂÈÙ·¯‡ÓÂÈ ÙË Ï‹„Ë ÙˆÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ, ‰ÂÓ ··ÈÙ› ÚÔËÁÔ‡ÌÂÓË Î·ÏÏȤÚÁÂÈ· ÙÔ˘ ˘fi ÌÂϤÙË ˘ÏÈÎÔ‡ Î·È ÂÍ·ÛÊ·Ï›˙ÂÈ ÈηÓÔÔÈËÙÈÎfi ·ÚÈıÌfi ΢ÙÙ¿ÚˆÓ ÁÈ· ÌÂϤÙË. ∂ÈϤÔÓ, Ì ÙËÓ Ù¯ÓÈ΋ FISH Â›Ó·È ‰˘Ó·Ù‹ Ë ·Ó›¯Ó¢ÛË Ôχ ÌÈÎÚÔ‡ ÌÂÁ¤ıÔ˘˜ (<3 ªµ) ¯ÚˆÌÔÛˆÌÈÎÒÓ ·Ó·Î·Ù·Ù¿ÍÂˆÓ ‹ ÂÏÏ›„ˆÓ, fiÙ·Ó ‰Â Û˘Ó‰˘·ÛÙ› Ì ·ÓÔÛÔÊ·ÈÓÔÙ˘È΋ ¯ÚÒÛË ÙˆÓ Î˘ÙÙ¿ÚˆÓ (Ì ·ÓÔÛÔ˚ÛÙÔ¯ËÌ›·) (Fluorescence Immunophenotyping and Interphase Cytogenetics - FICTION), ÂÈÙÚ¤ÂÈ ÙËÓ Ù·˘Ùfi¯ÚÔÓË Ù·˘ÙÔÔ›ËÛË ·ÓÔÛÔÊ·ÈÓÔÙ˘ÈÎÒÓ ‰ÂÈÎÙÒÓ Î·È ÁÂÓÂÙÈÎÒÓ ·ÓˆÌ·ÏÈÒÓ Û ÌÂÌÔӈ̤ӷ Ï¢¯·ÈÌÈο ·ÙÙ·Ú· (∂ÈÎfiÓ· 2). ∏ ·Ï˘ÛȉˆÙ‹ ·ÓÙ›‰Ú·ÛË ÔÏ˘ÌÂÚ¿Û˘ (PCR) ¯ÚËÛÈÌÔÔÈÂ›Ù·È ÁÈ· ÙËÓ Â‡ÚÂÛË ÛËÌÂÈ·ÎÒÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ Î·È ‰ÔÌÈÎÒÓ ·ÓˆÌ·ÏÈÒÓ Ô˘ ‰ÂÓ ·ÓȯÓ‡ÔÓÙ·È Ì ÙÔÓ Î·Ú˘fiÙ˘Ô. ¶ÚfiÎÂÈÙ·È ÁÈ· ȉȷ›ÙÂÚ· ¢·›ÛıËÙË Ì¤ıÔ‰Ô, Ì ÙËÓ ÔÔ›· ÂÈÙ˘Á¯¿ÓÂÙ·È Ë Â‡ÚÂÛË ·ÎfiÌ· Î·È ÂÓfi˜ Ï¢¯·ÈÌÈÎÔ‡ ΢ÙÙ¿ÚÔ˘ ÌÂٷ͇ 105 Î·È 106 Ê˘ÛÈÔÏÔÁÈÎÒÓ Î·È ¯ÚËÛÈ̇ÂÈ Î·È ÁÈ· ÙËÓ ·Ó›¯Ó¢ÛË ˘ÔÏÂÈfiÌÂÓ˘ ÓfiÛÔ˘ (42). ∆fiÛÔ Ë Ù¯ÓÈ΋ FISH fiÛÔ Î·È Ô ÌÔÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ Ì PCR ¤¯Ô˘Ó ÙË ‰˘Ó·ÙfiÙËÙ· Ó· ·ÓȯÓÂ‡Ô˘Ó Û˘ÁÎÂÎÚÈ̤Ó˜ ÁÂÓÂÙÈΤ˜ ‚Ï¿‚˜ ‹ ÌÂÙ·ÙÔ›ÛÂȘ, ÁÈ· ÙȘ Ôԛ˜ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ÂȉÈÎÔ› DNA ·ÓȯÓÂ˘Ù¤˜ ‹ ÂÎÎÈÓËÙ¤˜. ∏ ÓÂfiÙÂÚË Ù¯ÓÈ΋ ÙˆÓ ÌÈÎÚÔÛ˘ÛÙÔȯÈÒÓ Û˘ÁÎÚÈÙÈÎÔ‡ ÁÂÓˆÌÈÎÔ‡ ˘‚ÚȉÈÛÌÔ‡ (CGH arrays) ¯ÚËÛÈÌÔÔÈÂ›Ù·È Û‹ÌÂÚ· ¢ڤˆ˜ ÁÈ· ÙËÓ ·Ó›¯Ó¢ÛË ¯ÚˆÌÔÛˆÌÈÎÒÓ ÂÏÏÂÈÌÌ¿ÙˆÓ, ‰ÈÏ·ÛÈ·ÛÌÒÓ ‹ ·Ó·Î·Ù·Ù¿ÍˆÓ. ∏ ̤ıÔ‰Ô˜ ¤¯ÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· ÌÂϤÙ˘ ÂηÙÔÓÙ¿‰ˆÓ ¯ÚˆÌÔÛˆÌÈÎÒÓ ı¤ÛÂˆÓ Î·È ÁÔÓȉ›ˆÓ Û ¤Ó· ÌfiÓÔ ›ڷ̷, Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ·Ó›¯Ó¢ÛË ÁÓˆÛÙÒÓ ·ÓˆÌ·ÏÈÒÓ Ô˘ ÂÌϤÎÔÓÙ·È ÛÙËÓ ÂÌÊ¿ÓÈÛË Ù˘ ÓfiÛÔ˘, ·ÏÏ¿ Î·È ÙË ‰È·›ÛÙˆÛË Ó¤ˆÓ ¯ÚˆÌÔÛˆÌÈÎÒÓ ı¤ÛÂˆÓ Ô˘ Èı·ÓÒ˜ ¢ı‡ÓÔÓÙ·È ÁÈ· ÙËÓ ·ÈÙÈÔ·ıÔÁ¤ÓÂÈ· Î·È ÙËÓ ÂͤÏÈÍË Ù˘ √§§ Ù˘ ·È‰È΋˜ ËÏÈΛ·˜. π‰È·›ÙÂÚÔ ÂӉȷʤÚÔÓ ·ÚÔ˘ÛÈ¿˙ÂÈ Ë ÂÊ·ÚÌÔÁ‹ Ù˘ Ù¯ÓÈ΋˜ ÛÙËÓ ·Ó›¯Ó¢ÛË ÁÔÓȉ›ˆÓ Ô˘ Â›Ó·È ˘‡ı˘Ó· ÁÈ· ÙËÓ ·ÓÙÔ¯‹ Ô˘ ·ÚÔ˘ÛÈ¿˙Ô˘Ó Î¿ÔÈÔÈ ·ÛıÂÓ›˜ ÛÙ· ¯ËÌÂÈÔıÂÚ·¢ÙÈο Û¯‹Ì·Ù· ‹ ÙËÓ ÂÌÊ¿ÓÈÛË ‰Â˘ÙÂÚÔ·ıÒÓ Î·ÎÔËıÂÈÒÓ

Pediatri Jul-Aug 08

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‡ÛÙÂÚ· ·fi ¯ËÌÂÈÔıÂÚ·›·. √È Ì¤¯ÚÈ Û‹ÌÂÚ· ÌÂϤÙ˜ ¤¯Ô˘Ó ‰Â›ÍÂÈ fiÙÈ Ë ·ÓÙÔ¯‹ ÛÙË ¯ËÌÂÈÔıÂÚ·›· ‰ÂÓ ÔÊ›ÏÂÙ·È Û ¤Ó· ÌfiÓÔ ÁÔÓ›‰ÈÔ, ·ÏÏ¿ Û ÔÌ¿‰Â˜ ÁÔÓȉ›ˆÓ Ô˘ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙË ‰È·‰Èηۛ· Ù˘ ÌÂÙ·ÁÚ·Ê‹˜, Ù˘ ÂȉÈfiÚıˆÛ˘ ÙÔ˘ DNA, ÙÔ˘ ΢ÙÙ·ÚÈÎÔ‡ ·ÎÏÔ˘ Î·È ÙÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙˆÓ ÓÔ˘ÎÏÂ˚ÓÈÎÒÓ ÔͤˆÓ (46).

™˘ÌÂÚ¿ÛÌ·Ù· ∏ ÌÂÁ¿ÏË ÚfiÔ‰Ô˜ ÛÙÔÓ ÙÔ̤· Ù˘ ÁÂÓÂÙÈ΋˜ Î·È Ù˘ ·ÓÔÛÔÏÔÁ›·˜ ¤¯ÂÈ ‚ÔËı‹ÛÂÈ ÛÙËÓ Î·Ï‡ÙÂÚË Ù·ÍÈÓfiÌËÛË Ù˘ √§§, Ô˘ ·ÚÔ˘ÛÈ¿˙ÂÈ ÂÍ·ÈÚÂÙÈ΋ ÂÙÂÚÔÁ¤ÓÂÈ·, ÏfiÁˆ ÙˆÓ ÔÏÏÒÓ Î·È ‰È·ÊÔÚÂÙÈÎÒÓ ·ÓÔÛÔÊ·ÈÓÔÙ˘ÈÎÒÓ, ÌÔÚÈ·ÎÒÓ Î·È ¯ÚˆÌÔÛˆÌÈÎÒÓ Â˘ÚËÌ¿ÙˆÓ. ∏ ¯ÚˆÌÔÛˆÌÈ΋ ·Ó¿Ï˘ÛË ÙˆÓ ·ÛıÂÓÒÓ Ì √§§ ·ÔÙÂÏ› ÛËÌ·ÓÙÈÎfi ÂÚÁ·ÏÂ›Ô ÁÈ· ÙËÓ ·Ó›¯Ó¢ÛË ÂÚÈÔ¯ÒÓ Ô˘ ÂÚȤ¯Ô˘Ó ÁÔÓ›‰È· Ì›˙ÔÓÔ˜ ÛËÌ·Û›·˜ ÁÈ· ÙË ‰È·‰Èηۛ· Ù˘ Ï¢¯·ÈÌÔÁ¤ÓÂÛ˘. ∆· ΢ÙÙ·ÚÔÁÂÓÂÙÈο ¯·Ú·ÎÙËÚÈÛÙÈο, ÙÔ Â›‰Ô˜ ÙˆÓ ¯ÚˆÌÔÛˆÌÈÎÒÓ ·ÓˆÌ·ÏÈÒÓ ‹ Ô Ù‡Ô˜ ÙˆÓ ÌÂÙ·ÏÏ¿ÍÂˆÓ ‰È·Ê¤ÚÔ˘Ó ÛËÌ·ÓÙÈο ÛÙÔ˘˜ ˘ÔÙ‡Ô˘˜ Ù˘ √§§. ∂›Û˘, ˘¿Ú¯ÂÈ ÈÛ¯˘Ú‹ Û˘Û¯¤ÙÈÛË ÙˆÓ Î˘ÙÙ·ÚÔÁÂÓÂÙÈÎÒÓ ¯·Ú·ÎÙËÚÈÛÙÈÎÒÓ Ì ÙËÓ ÎÏÈÓÈ΋ ÂÈÎfiÓ·, ÙÔÓ ·ÓÔÛÔÊ·ÈÓfiÙ˘Ô, ÙËÓ ÚfiÁÓˆÛË Ù˘ ÓfiÛÔ˘ Î·È ÙËÓ ÂÈÏÔÁ‹ ÙÔ˘ ηٿÏÏËÏÔ˘ ıÂÚ·¢ÙÈÎÔ‡ Û¯‹Ì·ÙÔ˜, ¤ÙÛÈ ÒÛÙÂ Ô ·ÛıÂÓ‹˜ Ó· ¤¯ÂÈ ÙËÓ Î·Ï‡ÙÂÚË ·ÓÙ·fiÎÚÈÛË Ì ÙȘ ÏÈÁfiÙÂÚ˜ ·ÚÂÓ¤ÚÁÂȘ. ∂Ô̤ӈ˜, Ë ÁÓÒÛË Ù˘ ÌÔÚȷ΋˜ ‚¿Û˘ Ù˘ √§§ ‚ÔËı¿ÂÈ ÛÙËÓ Î·Ï‡ÙÂÚË Î·Ù·ÓfiËÛË Ù˘ ·ÈÙÈÔ·ıÔÁ¤ÓÂÈ·˜ Ù˘ ÓfiÛÔ˘ Î·È ÛÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙÂÚË ıÂÚ·¢ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË (47). µÈ‚ÏÈÔÁÚ·Ê›· 1. ∆˙ˆÚÙ˙¿ÙÔ˘-™Ù·ıÔÔ‡ÏÔ˘ º. ¶·È‰È·ÙÚÈ΋ √ÁÎÔÏÔÁ›·. π·ÙÚÈΤ˜ ÂΉfiÛÂȘ ¶. ¶·Û¯·Ï›‰Ë; 1997. ÛÂÏ. 20-23.

2. Kebriaei P, Anastasi J, Larson RA. Acute lymphoblastic leukaemia: diagnosis and classification. Best Pract Res Clin Haematol 2002;15:597-621.

3. McKenna RW. Multifaceted approach to the diagnosis and classification of acute leukemias. Clin Chem 2000;46:12521259.

4. Basso G, Buldini B, De Zen L, Orfao A. New methodologic approaches for immunophenotyping acute leukemias.

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41. Kanerva J, Niini T, Vettenranta K, Riikonen P, Mäkipernaa A, Karhu R, et al. Loss at 12p detected by comparative genomic hybridization (CGH): association with TEL-AML1 fusion and favorable prognostic features in childhood acute lymphoblastic leukemia (ALL). A multi-institutional study. Med Pediatr Oncol 2001;37:419-425.

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∫˘ÙÙ·ÚÔÁÂÓÂÙÈο Â˘Ú‹Ì·Ù· ÛÙȘ Ï¢¯·È̛˜ Ù˘ ·È‰È΋˜ ËÏÈΛ·˜ ∞. °·ÏÏ¿-µÔ˘Ì‚Ô˘Ú¿ÎË ¶ÂÚ›ÏË„Ë: ∫·Ù¿ ÙË ‰È¿ÚÎÂÈ· ÙˆÓ ‰‡Ô ÙÂÏÂ˘Ù·›ˆÓ ‰ÂηÂÙÈÒÓ ¤¯ÂÈ ÙÂÎÌËÚȈı› Ë ÛËÌ·ÓÙÈ΋ Û¯¤ÛË Ô˘ ˘¿Ú¯ÂÈ ÌÂٷ͇ Û˘ÁÎÂÎÚÈÌ¤ÓˆÓ ¯ÚˆÌÔÛˆÌÈÎÒÓ ·ÓˆÌ·ÏÈÒÓ Î·È Ù˘ ÔÍ›·˜ Ï¢¯·ÈÌ›·˜ ÛÙËÓ ·È‰È΋ ËÏÈΛ·. ∂ÈϤÔÓ, Ì ÙË ‚Ô‹ıÂÈ· Ù˘ ÌÔÚȷ΋˜ ‚ÈÔÏÔÁ›·˜, ¤¯ÂÈ ÂÈÙ¢¯ı› Ë Ù·˘ÙÔÔ›ËÛË ÙˆÓ ÁÔÓȉ›ˆÓ, Ë ÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ÔÔ›ˆÓ ‰È·Ù·Ú¿ÛÛÂÙ·È ÏfiÁˆ ÙˆÓ ¯ÚˆÌÔÛˆÌÈÎÒÓ ·˘ÙÒÓ ‰È·Ù·Ú·¯ÒÓ. £ÂˆÚÂ›Ù·È fiÙÈ Ë ÛˆÛÙ‹ ·ÍÈÔÏfiÁËÛË ÙˆÓ ¯ÚˆÌÔÛˆÌÈÎÒÓ ‰È·Ù·Ú·¯ÒÓ Î·È ÙˆÓ ÂÈÙÒÛÂÒÓ ÙÔ˘˜ Û ÌÔÚÈ·Îfi Â›Â‰Ô ÌÔÚ› Ó· Û˘Ì‚¿ÏÏÂÈ ÛËÌ·ÓÙÈο ÛÙËÓ Ù·ÍÈÓfiÌËÛË, ÙËÓ ÚfiÁÓˆÛË Î·È ÙË ıÂÚ·¢ÙÈ΋ ÚÔÛ¤ÁÁÈÛË ÙˆÓ Î·ÎÔËıÂÈÒÓ ÙÔ˘ ·ÈÌÔÔÈËÙÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜. ™ÎÔfi˜ Ù˘ ·Ó·ÛÎfiËÛ˘ ·˘Ù‹˜ Â›Ó·È Ó· ·ÚÔ˘ÛÈ·ÛÙÔ‡Ó ÔÈ ϤÔÓ Û˘¯Ó¤˜ ¯ÚˆÌÔÛˆÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ Ô˘ ¤¯Ô˘Ó ·Ú·ÙËÚËı› ÛÙȘ ÔÍ›˜ Ï¢¯·È̛˜ Ù˘ ·È‰È΋˜ ËÏÈΛ·˜.

∆Ì‹Ì· °ÂÓÂÙÈ΋˜, µ' ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡” AÏÏËÏÔÁÚ·Ê›·: ∞ÁÁÂÏÈ΋ °·ÏÏ¿-µÔ˘Ì‚Ô˘Ú¿ÎË ∆Ì‹Ì· °ÂÓÂÙÈ΋˜, µ’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”

§¤ÍÂȘ ÎÏÂȉȿ: ÃÚˆÌÔÛˆÌÈΤ˜ ‰È·Ù·Ú·¯¤˜, ÔÍ›· Ï¢¯·ÈÌ›·, ·È‰È¿.

Cytogenetic abnormalities in leukaemias of childhood ∞. Galla-Voumvouraki Abstract: During the past two decades, the close association between specific chromosomal abnormalities and acute childhood leukaemias has been established and identification of clonal rearrangements of the involved genes has been made by molecular biology assays. It is suggested that detailed evaluation of the chromosomal rearrangements and the genes involved could contribute to the classification, prognosis and treatment of cancer of the haematopoetic system. This is a review of the most frequent chromosomal abnormalities associated with childhood leukaemias.

Key words: Chromosomal abnormalities, acute leukaemias, children.

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∂ÈÛ·ÁˆÁ‹ √È Ï¢¯·È̛˜ Â›Ó·È Ë ÈÔ Û˘¯Ó‹ ηÎÔ‹ı˘ ÓfiÛÔ˜ ÛÙ· ·È‰È¿ Î·È ·ÓÙÈÚÔÛˆÂ‡Ô˘Ó ÙÔ 33% ÙˆÓ Î·ÎÔËıÂÈÒÓ Ù˘ ·È‰È΋˜ ËÏÈΛ·˜. ¶·ÁÎÔÛÌ›ˆ˜, Ë ÂÙ‹ÛÈ· Û˘¯ÓfiÙËÙ¿ ÙÔ˘˜ ·Ó¤Ú¯ÂÙ·È Û 42,1/1.000.000 Î·È 24,3/1.000.000 ·È‰È¿ Ù˘ Ï¢΋˜ Î·È Ù˘ Ì·‡Ú˘ Ê˘Ï‹˜, ·ÓÙÈÛÙÔ›¯ˆ˜ (1). ∫‡ÚÈÔ˜ ÂÎÚfiÛˆÔ˜ ÙˆÓ Ï¢¯·ÈÌÈÒÓ Ù˘ ·È‰È΋˜ ËÏÈΛ·˜ Â›Ó·È Ë ÔÍ›· ÏÂÌÊÔ‚Ï·ÛÙÈ΋ Ï¢¯·ÈÌ›·. √Í›· ÏÂÌÊÔ‚Ï·ÛÙÈ΋ Ï¢¯·ÈÌ›· ∏ ÔÍ›· ÏÂÌÊÔ‚Ï·ÛÙÈ΋ Ï¢¯·ÈÌ›· (√§§) ·ÔÙÂÏ› ÙÔ 75% ÙˆÓ ÂÚÈÙÒÛÂˆÓ Ï¢¯·ÈÌ›·˜ Ù˘ ·È‰È΋˜ ËÏÈΛ·˜ Î·È ¤¯ÂÈ Ôχ ηϋ ÚfiÁÓˆÛË (1). ™ÙÔ ÁÂÓÂÙÈÎfi ˘ÏÈÎfi ÙˆÓ ‚Ï·ÛÙÒÓ ‰È·ÈÛÙÒÓÔÓÙ·È ¯ÚˆÌÔÛˆÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ Û ÂÚÈÛÛfiÙÂÚ˜ ·fi 90% ÙˆÓ ÂÚÈÙÒÛÂˆÓ ÌÂ

Department of Genetics, 2nd Department of Paediatrics, University of Athens, “P. & A. Kyriakou” Children’s Hospital, Athens, Greece Correspondence: ∞ggeliki Galla-Voumvouraki Department of Genetics, 2nd Department of Paediatrics, University of Athens, “P. & A. Kyriakou” Children’s Hospital, Athens, Greece

Û˘Ó‰˘·Ṳ̂Ó˜ ÌÂıfi‰Ô˘˜ ÎÏ·ÛÈ΋˜/ÌÔÚȷ΋˜ ΢ÙÙ·ÚÔÁÂÓÂÙÈ΋˜ Î·È ÌÔÚȷΤ˜ Ù¯ÓÈΤ˜ (2). ∏ ¯ÚˆÌÔÛˆÌÈ΋ ·Ó¿Ï˘ÛË (ηڢfiÙ˘Ô˜) ÙˆÓ ‚Ï·ÛÙÒÓ ıˆÚÂ›Ù·È ÂȂ‚ÏË̤ÓË ÁÈ· ÙËÓ Ù·ÍÈÓfiÌËÛË, ÙË ıÂÚ·¢ÙÈ΋ ÚÔÛ¤ÁÁÈÛË Î·È ÙËÓ ÚfiÁÓˆÛË Ù˘ ÓfiÛÔ˘. √È ¯ÚˆÌÔÛˆÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ Ô˘ ‰È·ÈÛÙÒÓÔÓÙ·È ÛÙËÓ √§§ ‰È·ÎÚ›ÓÔÓÙ·È ÛÙȘ ·ÚÈıÌËÙÈΤ˜ Î·È ÙȘ ‰ÔÌÈΤ˜.

∞ÚÈıÌËÙÈΤ˜ ¯ÚˆÌÔÛˆÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÛÙËÓ √§§ ™ÙËÓ √§§, Ì ‚¿ÛË ÙÔÓ ·ÚÈıÌfi ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ÙˆÓ ‚Ï·ÛÙÒÓ ÛÙÔ Ì˘ÂÏfi ÙˆÓ ÔÛÙÒÓ, ‰È·ÎÚ›ÓÔÓÙ·È Î˘Ú›ˆ˜ 4 ηÙËÁÔڛ˜ Ì ÛËÌ·ÓÙÈ΋ ÚÔÁÓˆÛÙÈ΋ ·Í›· ÁÈ· ÙË ÓfiÛÔ (2-7). ™˘ÁÎÂÎÚÈ̤ӷ ÔÈ Î·ÙËÁÔڛ˜ ·˘Ù¤˜ Â›Ó·È Ô „¢‰Ô‰ÈÏÔÂȉÈÛÌfi˜ (pseudodiploidy), Ô ÔÏ˘ÏÔÂȉÈÛÌfi˜ (hyperdirploidy), Ô ‰ÈÏÔÂȉÈÛÌfi˜ (diploidy) Î·È Ô ˘Ô‰ÈÏÔÂȉÈÛÌfi˜ (hypodiploidy) Î·È ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Î·Ù¿ ÛÂÈÚ¿ Û˘¯ÓfiÙËÙ·˜ ÛÙÔÓ ¶›Ó·Î· 1. ø˜ „¢‰Ô‰ÈÏÔÂȉÈÛÌfi˜ ÔÚ›˙ÂÙ·È Ë ·ÚÔ˘Û›· ÛÙÔ˘˜ ‚Ï¿ÛÙ˜ 46 ¯ÚˆÌÔۈ̿وÓ, ·ÏÏ¿ ¯ˆÚ›˜ Ó· ÂÎÚÔÛˆÔ‡ÓÙ·È fiÏ· Ù· ˙‡ÁË ÙˆÓ ¶·È‰È·ÙÚÈ΋ 2008;71:263-270

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46 51-68 47-50 46 <46

40 26 14 12 8

¯ÚˆÌÔۈ̿وÓ, fiˆ˜ Û˘Ì‚·›ÓÂÈ ÛÙÔ Ê˘ÛÈÔÏÔÁÈÎfi ηڢfiÙ˘Ô. ∂›Ó·È ‰˘Ó·Ùfi, ‰ËÏ·‰‹, Ó· ˘¿Ú¯ÂÈ Ù·˘Ùfi¯ÚÔÓ· ÂÚ›ÛÛÂÈ· οÔÈÔ˘ Î·È ¤ÏÏÂÈ„Ë Î¿ÔÈÔ˘ ¿ÏÏÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜. √ „¢‰Ô‰ÈÏÔÂȉÈÛÌfi˜ ·Ú·ÙËÚÂ›Ù·È ÛÙÔ 40% ÙˆÓ ÂÚÈÙÒÛÂˆÓ √§§ Î·È ¯·Ú·ÎÙËÚ›˙ÂÈ ÌÂÁ¿ÏË ÂÙÂÚÔÁÂÓ‹ ÔÌ¿‰· ·ÛıÂÓÒÓ Ì ÌÂÁ¿ÏÔ ·ÚÈıÌfi Ï¢ÎÒÓ ·ÈÌÔÛÊ·ÈÚ›ˆÓ Î·È ·˘ÍË̤ӷ Â›‰· Á·Ï·ÎÙÈ΋˜ ‰Â¸‰ÚÔÁÂÓ¿Û˘. √È ·ÛıÂÓ›˜ Ì „¢‰Ô‰ÈÏÔÂȉÈÛÌfi ¤¯Ô˘Ó Ôχ η΋ ÚfiÁÓˆÛË, ÂÎÙfi˜ Â¿Ó ˘Ô‚ÏËıÔ‡Ó Û ÂȉÈο Û˘Ó‰˘·Ṳ̂ӷ ¯ËÌÂÈÔıÂÚ·¢ÙÈο Û¯‹Ì·Ù·, ÔfiÙ ¤¯Ô˘Ó ÙËÓ ›‰È· ·ÎÚÈ‚Ò˜ ·ÓÙ·fiÎÚÈÛË Ì ÙȘ ¿ÏϘ ÔÌ¿‰Â˜ ·ÛıÂÓÒÓ (8,9). ∂Í·›ÚÂÛË ·ÔÙÂÏÔ‡Ó ÔÈ ·ÛıÂÓ›˜ Ì ÙȘ ¯ÚˆÌÔÛˆÌÈΤ˜ ÌÂÙ·ı¤ÛÂȘ t(9;22) Î·È t(4;11), ÔÈ ÔÔ›ÔÈ ÂÌÊ·Ó›˙Ô˘Ó ÓfiÛÔ ·ÓıÂÎÙÈ΋ ÛÙ· ¯ËÌÂÈÔıÂÚ·¢ÙÈο Û¯‹Ì·Ù· (2). ™ÙÔÓ ÔÏ˘ÏÔÂȉÈÛÌfi Ô ·ÚÈıÌfi˜ ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ÙˆÓ ‚Ï·ÛÙÒÓ Î˘Ì·›ÓÂÙ·È ·fi 47 ¤ˆ˜ 92 Î·È ·Ó¿ÏÔÁ· Ì ÙÔÓ ·ÚÈıÌfi ‰È·ÎÚ›ÓÔÓÙ·È ˘ÔηÙËÁÔڛ˜ Ì ȉȷ›ÙÂÚ·, Û οı ̛·, ¯·Ú·ÎÙËÚÈÛÙÈο. ™˘ÁÎÂÎÚÈ̤ӷ, Ô ÔÏ˘ÏÔÂȉÈÛÌfi˜ Ì ·ÚÈıÌfi ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ·fi 51 ¤ˆ˜ 68 ·ÔÙÂÏ› ÙÔ ϤÔÓ Û˘¯Ófi ‡ÚËÌ·. ¶·Ú·ÙËÚÂ›Ù·È ÛÙÔ 26% ÙˆÓ ·ÛıÂÓÒÓ Ì √§§, ΢ڛˆ˜ Û ·È‰È¿ ËÏÈΛ·˜ 2-10 ÂÙÒÓ Ì ۯÂÙÈο ÌÈÎÚfi ·ÚÈıÌfi Ï¢ÎÒÓ ·ÈÌÔÛÊ·ÈÚ›ˆÓ Î·È ÚÔ-µ ·ÓÔÛÔÊ·ÈÓfiÙ˘Ô ÙˆÓ ‚Ï·ÛÙÒÓ (4,10,11). ∆· ¯ÚˆÌÔÛÒÌ·Ù· (¯Ú) Ù· ÔÔ›· ˘¿Ú¯Ô˘Ó Û ÂÚ›ÛÛÂÈ· Â›Ó·È Î·Ù¿ ÛÂÈÚ¿ Û˘¯ÓfiÙËÙ·˜ ÙÔ ¯Ú≠21 (97%), ¯Ú≠6 (86%), ¯Ú≠à (81%), ¯Ú≠14 (80%), ¯Ú≠4 (76%), ¯Ú≠17 (68%), ¯Ú≠18 (68%), ¯Ú≠10 (56%), ¯Ú≠8 (34%) Î·È ¯Ú≠5 (26%) (12). √ ÔÏ˘ÏÔÂȉÈÛÌfi˜ Û¯ÂÙ›˙ÂÙ·È Ì ÙËÓ Î·Ï‡ÙÂÚË ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘, ȉȷ›ÙÂÚ· fiÙ·Ó ˘¿Ú¯ÂÈ ÙÚÈۈ̛· ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ≠4 Î·È ≠10 (13). ∞ӷʤÚÂÙ·È Ì¿ÏÈÛÙ· fiÙÈ ÔÈ ·ÛıÂÓ›˜ Ì √§§ Î·È ÔÏ˘ÏÔÂȉÈÛÌfi Ù˘ Ù¿Í˘ ÙˆÓ 56 ¤ˆ˜ 68 ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ¤¯Ô˘Ó ηχÙÂÚË ÚfiÁÓˆÛË, Û ۯ¤ÛË Ì ÂΛÓÔ˘˜ ÛÙÔ˘˜ ÔÔ›Ô˘˜ Ô ·ÚÈıÌfi˜ ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ Â›Ó·È 51 ¤ˆ˜ 55 (22). ™Â in vitro ÌÂϤÙË ·fi ÙÔ˘˜ Whitehead Î·È Û˘Ó.

(1994) ‰È·ÈÛÙÒıËÎ·Ó ˘„ËÏfiÙÂÚ˜ Û˘ÁÎÂÓÙÚÒÛÂȘ ÌÂıÔÙÚÂÍ¿Ù˘ Î·È ÙˆÓ ÔÏ˘ÁÏÔ˘Ù·ÌÈÓÈÎÒÓ ·Ú·ÁÒÁˆÓ Ù˘ ÛÙȘ ÂÚÈÙÒÛÂȘ ‚Ï·ÛÙÒÓ Ì 56 ¤ˆ˜ 65 ·ÚÈıÌfi ¯ÚˆÌÔۈ̿وÓ, Û ۇÁÎÚÈÛË Ì ÂΛÓÔ˘˜ ÛÙÔ˘˜ ÔÔ›Ô˘˜ Ô ÔÏ˘ÏÔÂȉÈÛÌfi˜ ‹Ù·Ó Ù˘ Ù¿Í˘ ÙˆÓ 51 ¤ˆ˜ 55 ¯ÚˆÌÔÛˆÌ¿ÙˆÓ (14). ¶Èı·ÓÔÏÔÁÂ›Ù·È Paediatriki 2008;71:263-270

ÂÔ̤ӈ˜ fiÙÈ ÔÈ ‚Ï¿ÛÙ˜ Ì ÙÔ ÌÂÁ·Ï‡ÙÂÚÔ ·ÚÈıÌfi ¯ÚˆÌÔÛˆÌ¿ÙˆÓ Â›Ó·È ÈÔ Â˘·›ÛıËÙÔÈ ÛÙÔ ¯ËÌÂÈÔıÂÚ·¢ÙÈÎfi ·Ú¿ÁÔÓÙ· ÌÂıÔÙÚÂÍ¿ÙË. ∞Í›˙ÂÈ Ó· ·Ó·ÊÂÚı› fiÙÈ, ‰Â‰Ô̤ÓÔ˘ fiÙÈ ÔÏϤ˜ ÊÔÚ¤˜ Ì ÙȘ ÎÏ·ÛÈΤ˜ ΢ÙÙ·ÚÔÁÂÓÂÙÈΤ˜ ÌÂıfi‰Ô˘˜ ‰ÂÓ Â›Ó·È ‰˘Ó·Ù‹ Ë Ù·˘ÙÔÔ›ËÛË ÙˆÓ ¯ÚˆÌÔÛˆÌÈÎÒÓ ‰È·Ù·Ú·¯ÒÓ ÛÙËÓ √§§, ·fi ÔÚÈṲ̂Ó˜ ÂÚ¢ÓËÙÈΤ˜ ÔÌ¿‰Â˜, fiˆ˜ ÂΛÓË Ù˘ ∫˘ÙÙ·ÚÔÁÂÓÂÙÈ΋˜ ÙÔ˘ ∫·ÚΛÓÔ˘ Ù˘ ªÂÁ¿Ï˘ µÚÂÙ·Ó›·˜, Û˘ÓÈÛÙ¿Ù·È Ë ÂÊ·ÚÌÔÁ‹ ¿ÏÏ˘ Ú·ÎÙÈ΋˜. ™˘ÁÎÂÎÚÈ̤ӷ, Û˘ÛÙ‹ÓÂÙ·È Ó· ¯ÚËÛÈÌÔÔÈÂ›Ù·È Ë ÌÔÚȷ΋ ΢ÙÙ·ÚÔÁÂÓÂÙÈ΋ ̤ıÔ‰Ô˜ ÙÔ˘ ÊıÔÚÈÛÌÔ‡ Ì in situ ˘‚ÚȉÈÛÌfi (FISH) Û ÌÂÛÔÊ·ÛÈο (interphase) ·ÙÙ·Ú· ÛÙȘ ÂÚÈÙÒÛÂȘ √§§ Ì ·ÚÈıÌfi ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ÌÂÁ·Ï‡ÙÂÚÔ ÙÔ˘ 50. √ ÛÎÔfi˜ Â›Ó·È Ë ÁÚ‹ÁÔÚË ·Ó›¯Ó¢ÛË Èı·Ó‹˜ ÙÚÈۈ̛·˜ ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ≠4 Î·È ≠10, ÒÛÙ ӷ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ϤÔÓ ‹È· ¯ËÌÂÈÔıÂÚ·¢ÙÈο Û¯‹Ì·Ù· (13,15,16). ∞ӷʤÚÂÙ·È Â›Û˘ ·fi ÙËÓ ·Ú·¿Óˆ ÂÚ¢ÓËÙÈ΋ ÔÌ¿‰· fiÙÈ Ë Û˘ÁÎÂÎÚÈ̤ÓË Ù¯ÓÈ΋ ı· ÌÔÚÔ‡Û ӷ ÂÊ·ÚÌÔÛı› Î·È ˆ˜ ̤ıÔ‰Ô˜ Ù·˘ÙÔÔ›ËÛ˘ Ù˘ ˘ÔÏÂÈfiÌÂÓ˘ ÓfiÛÔ˘ √§§ (minimal residual disease) (13,15,16). ™ÙÔ 10-15% ÙˆÓ ÂÚÈÙÒÛÂˆÓ √§§ ·Ú·ÙËÚÂ›Ù·È ÔÏ˘ÏÔÂȉÈÛÌfi˜ Ù˘ Ù¿Í˘ ÙˆÓ 47-50 ¯ÚˆÌÔۈ̿وÓ. ™ÙȘ ÂÚÈÙÒÛÂȘ ·˘Ù¤˜, Ù· ¯ÚˆÌÔÛÒÌ·Ù· Ô˘ ˘ÂÚÂÎÚÔÛˆÔ‡ÓÙ·È Â›Ó·È Î·Ù¿ ÛÂÈÚ¿ Û˘¯ÓfiÙËÙ·˜ ÙÔ ¯ÚˆÌfiۈ̷ ≠21, ≠10 Î·È ≠8. £ÂˆÚÂ›Ù·È fiÙÈ Ô ÔÏ˘ÏÔÂȉÈÛÌfi˜ ·˘Ùfi˜ Û¯ÂÙ›˙ÂÙ·È Ì ηϋ ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘, ȉȷ›ÙÂÚ· Â› ÙÚÈۈ̛·˜ 21, ÂÓÒ Ë ÙÚÈۈ̛· 8 Û˘Ó‰˘¿˙ÂÙ·È Ì ∆-·ÓÔÛÔÊ·ÈÓfiÙ˘Ô Î·È ‰ÂÓ Â›Ó·È ·ÎÚÈ‚Ò˜ ÁÓˆÛÙ‹ Ë ÚÔÁÓˆÛÙÈ΋ Ù˘ ·Í›· (17,18,19). ¶Ú¤ÂÈ Ó· ·Ó·ÊÂÚı› fiÙÈ o ÔÏ˘ÏÔÂȉÈÛÌfi˜ Ì ·ÚÈıÌfi ¯ÚˆÌÔÛˆÌ¿ÙˆÓ Ù˘ Ù¿Í˘ ÙˆÓ 69 ¤ˆ˜ 81 ¯ÚˆÌÔÛˆÌ¿ÙˆÓ (near-triploidy) Â›Ó·È Ôχ Û¿ÓÈÔ˜ ÛÙËÓ √§§ (0,3%) Î·È ‰ÂÓ Ê·›ÓÂÙ·È Ó· Û¯ÂÙ›˙ÂÙ·È ÌÂ Û˘ÁÎÂÎÚÈ̤ӷ ÎÏÈÓÈο ‹ ·ÓÔÛÔÊ·ÈÓÔÙ˘Èο ¯·Ú·ÎÙËÚÈÛÙÈο, ÂÎÙfi˜ ·fi ÌÈ· ÌÈÎÚ‹ ˘ÂÚÔ¯‹ ÙÔ˘ ÚÔ-µ ·ÓÔÛÔÊ·ÈÓÔÙ‡Ô˘ (20). ∂›Û˘, Ô ÔÏ˘ÏÔÂȉÈÛÌfi˜ Ì ·ÚÈıÌfi ¯ÚˆÌÔÛˆÌ¿ÙˆÓ Ô˘ Î˘Ì·›ÓÂÙ·È ·fi 82-94 (near-tetraploidy) Â›Ó·È Ôχ Û¿ÓÈÔ˜ ÛÙËÓ √§§ (<1%). ™ÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ, ÚfiÎÂÈÙ·È ÁÈ· ¯ÚˆÌÔÛˆÌÈÎfi ÂÓ‰Ô·Ó·‰ÈÏ·ÛÈ·ÛÌfi (endoreduplication), ÂÓÒ Û¯ÂÙ›˙ÂÙ·È Ì ÌÂÁ·Ï‡ÙÂÚË ËÏÈΛ· ·È‰ÈÒÓ, L2 ‚Ï¿ÛÙ˜ Î·È ∆-·ÓÔÛÔÊ·ÈÓfiÙ˘Ô (2). °ÂÓÈÎfiÙÂÚ·, ıˆÚÂ›Ù·È fiÙÈ Ë Î·Ï‹ ¤Î‚·ÛË Ù˘ √§§ ÛÙ· ·È‰È¿ Ì ˘ÂÚ‰ÈÏÔÂȉÈÛÌfi Èı·Ófiٷٷ ÔÊ›ÏÂÙ·È ÛÂ Û˘Ó‰˘·ÛÌfi ·Ú·ÁfiÓÙˆÓ, fiˆ˜ Ë ·˘ÍË̤ÓË Û˘ÁΤÓÙÚˆÛË ÛÙÔ˘˜ ‚Ï¿ÛÙ˜ ÙˆÓ ÔÏ˘ÁÏÔ˘Ù·ÌÈÓÈÎÒÓ ·Ú·ÁÒÁˆÓ Ù˘ ÌÂıÔÙÚÂÍ¿Ù˘ (methotrexate polyglutanates), Ë ·˘ÍË̤ÓË Â˘·ÈÛıËÛ›· ÛÙÔ˘˜ ·ÓÙÈÌÂÙ·‚Ôϛ٘, ηıÒ˜ Î·È Ë ·˘ÍË̤ÓË ·fiÙˆÛË ÙˆÓ ‚Ï·ÛÙÒÓ (2).

Pediatri Jul-Aug 08

30-07-08

15:52

™ÂÏ›‰·265

265

°ÂÓÂÙÈ΋ Î·È Ï¢¯·ÈÌ›· ÛÙ· ·È‰È¿

¶›Ó·Î·˜ 2. ¢ÔÌÈΤ˜ ¯ÚˆÌÔÛˆÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÛÙËÓ √§§ ¢È·Ù·Ú·¯‹ ÃÚˆÌfiۈ̷ ≠12 (12p)

∂ÏÏ›ÌÌ·Ù· 12 p t(12;21) t(2;12) dic 9 (9;12) dic 7 (7;12) t(12;13) t(12;17)

ªÂÙ¿ıÂÛË

der 19 t(1;19) t(1;19)

ÃÚˆÌfiۈ̷ ≠11 (11q)

t(4;11) t(11;19) t(1;11) t(9;11) t(10;11)

ÃÚˆÌfiۈ̷ Philadelphia

t(9;22)

ÃÚˆÌfiۈ̷ ≠6 (6q)

∂ÏÏ›ÌÌ·Ù·

ÃÚˆÌfiۈ̷ ≠9 (9p)

∂ÏÏ›ÌÌ·Ù·

ªÂÙ¿ıÂÛË

t(8;14) t(2;8) t(8;22)

™ÙÔ 10-15% ÙˆÓ ÂÚÈÙÒÛÂˆÓ √§§ ·Ó¢ڛÛÎÂÙ·È Ê˘ÛÈÔÏÔÁÈÎfi˜ ·ÚÈıÌfi˜ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ Î·È ‰ÂÓ ·Ú·ÙËÚÔ‡ÓÙ·È Î˘ÙÙ·ÚÔÁÂÓÂÙÈΤ˜ ‰È·Ù·Ú·¯¤˜ Ì ÙȘ ÎÏ·ÛÈΤ˜ ÌÂıfi‰Ô˘˜ ΢ÙÙ·ÚÔÁÂÓÂÙÈ΋˜ ·Ó¿Ï˘Û˘ (4,17). ∆¤ÏÔ˜, ÛÙÔ 8% ÙˆÓ ÂÚÈÙÒÛÂˆÓ √§§ ·Ú·ÙËÚÂ›Ù·È ˘Ô‰ÈÏÔÂȉÈÛÌfi˜, ‰ËÏ·‰‹ ·ÚÈıÌfi˜ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ÌÈÎÚfiÙÂÚÔ˜ ÙÔ˘ 46. ™˘Ó‹ıˆ˜ ·Ó¢ڛÛÎÔÓÙ·È 45 ¯ÚˆÌÔÛÒÌ·Ù· Î·È Â›Ù ÚfiÎÂÈÙ·È ÁÈ· ¤ÏÏÂÈ„Ë ÔÏfiÎÏËÚÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ›Ù ÁÈ· ÌË ÈÛÔ˙˘ÁÈṲ̂ÓË ÌÂÙ¿ıÂÛË Â›Ù ÁÈ· ‰ËÌÈÔ˘ÚÁ›· ‰ÈÎÂÓÙÚÈÎÔ‡ ¯ÚˆÌÔÛÒÌ·ÙÔ˜. ™ÙȘ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ ÚfiÎÂÈÙ·È ÁÈ· ·ÒÏÂÈ· ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ≠20. √ ˘Ô‰ÈÏÔÂȉÈÛÌfi˜ Û¯ÂÙ›˙ÂÙ·È Ì η΋ ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘ Î·È Ì¿ÏÈÛÙ· ηٿ ÙÚfiÔ ·Ó¿ÏÔÁÔ Ì ÙÔÓ ·ÚÈıÌfi ÙˆÓ ¯ÚˆÌÔۈ̿وÓ. ™˘ÁÎÂÎÚÈ̤ӷ, fiÛÔ ÌÈÎÚfiÙÂÚÔ˜ Ô ·ÚÈıÌfi˜ ÙˆÓ ¯ÚˆÌÔۈ̿وÓ, ÙfiÛÔ ¯ÂÈÚfiÙÂÚË Ë ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘ (2,21-23).

¢ÔÌÈΤ˜ ¯ÚˆÌÔÛˆÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÛÙËÓ √§§ √È ‰ÔÌÈΤ˜ ¯ÚˆÌÔÛˆÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ Ô˘ ·Ú·ÙËÚÔ‡ÓÙ·È ÛÙËÓ √§§ ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È ·Ó·Ï˘ÙÈο ÛÙÔÓ ¶›Ó·Î· 2. ¢ÔÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 12 √È ‰ÔÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ¯Ú≠12 ·Ó¢ڛÛÎÔÓÙ·È ÛÙÔ 8-20% ÙˆÓ ·È‰ÈÒÓ Ì √§§. ∞ÊÔÚÔ‡Ó Î˘Ú›ˆ˜ ÙÔ

‚Ú·¯‡ ÛΤÏÔ˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ (12p) Î·È ÛÙÔ 25% ·ÊÔÚÔ‡Ó ÂÏÏ›ÌÌ·Ù· Ù˘ ÂÚÈÔ¯‹˜ (12p deletions). ∂›Û˘, Ì ·˘ÍË̤ÓË Û˘¯ÓfiÙËÙ· ·Ú·ÙËÚÔ‡ÓÙ·È ÌÂÙ·ı¤ÛÂȘ ÛÙÔ˘˜ Ù‡Ô˘˜ t(12;21), dic(9;12), dic(7;12) Î·È t(12;13). √È ÏÂÌÊÔ‚Ï¿ÛÙ˜ Ì ¯ÚˆÌÔÛˆÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ¯Ú≠12 ‰ÂÓ ¤¯Ô˘Ó Û˘ÁÎÂÎÚÈ̤ÓÔ ·ÓÔÛÔÊ·ÈÓfiÙ˘Ô, ÂÓÒ ‰ÂÓ ·Ú·ÙËÚÂ›Ù·È Û˘¯Ó¿ ˘ÂÚ‰ÈÏÔÂȉÈÛÌfi˜ Ì ·ÚÈıÌfi ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ÌÂÁ·Ï‡ÙÂÚÔ ÙÔ˘ 50. ∏ ÚfiÁÓˆÛË Ù˘ ÓfiÛÔ˘ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì √§§ Ì ÙȘ ¯ÚˆÌÔÛˆÌÈΤ˜ ·˘Ù¤˜ ‰È·Ù·Ú·¯¤˜ ‰ÂÓ ‰È·Ê¤ÚÂÈ Û˘ÁÎÚÈÙÈο Ì ¿ÏÏÔ˘˜ ·ÛıÂÓ›˜ Ì √§§ (2,24-26). π‰È·›ÙÂÚË ·Ó·ÊÔÚ¿ ı· Ú¤ÂÈ Ó· Á›ÓÂÈ ÛÙË ¯ÚˆÌÔÛˆÌÈ΋ ÌÂÙ¿ıÂÛË t(12;21)(p13;q22), Ë ÔÔ›· ‰ÂÓ ·Ó¢ڛÛÎÂÙ·È ÛÙÔ˘˜ ‚Ï¿ÛÙ˜ Ì ÙȘ ÎÏ·ÛÈΤ˜ ΢ÙÙ·ÚÔÁÂÓÂÙÈΤ˜ ÌÂıfi‰Ô˘˜, ÂÂȉ‹ ÚfiÎÂÈÙ·È ÁÈ· ¤ÏÏÂÈ„Ë ÙÂÏÔÌÂÚȉ›Ô˘, ·ÏÏ¿ ÌfiÓÔ Ì ÊıÔÚ›˙ÔÓÙ· in situ ˘‚ÚȉÈÛÌfi (FISH) ‹ Ì ÌÔÚȷΤ˜ Ù¯ÓÈΤ˜. ¶·Ú·ÙËÚÂ›Ù·È ÛÙÔ 20-25% ÙˆÓ ·È‰ÈÒÓ Î˘Ú›ˆ˜ 3-5 ÂÙÒÓ Ì √§§, Û¯ÂÙ›˙ÂÙ·È Ì µ-·ÓÔÛÔÊ·ÈÓfiÙ˘Ô Î·È ¤ÎÊÚ·ÛË ÙˆÓ ·ÓÙÈÁfiÓˆÓ CD13, CD33 Î·È Û¯ÂÙ›˙ÂÙ·È Ì ¿ÚÈÛÙË ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘. ™Â ÌÔÚÈ·Îfi Â›Â‰Ô ·fi ÙË ¯ÚˆÌÔÛˆÌÈ΋ ·˘Ù‹ ÌÂÙ¿ıÂÛË ÚÔ·ÙÂÈ ÁÔÓ›‰ÈÔ “Û‡ÓÙË͢” ÙˆÓ ÁÔÓȉ›ˆÓ TEL (¯Ú≠12p) Î·È ∞ªL1 (¯Ú≠21q), Ù· ÔÔ›· ·ÔÙÂÏÔ‡Ó ÌÂÙ·ÁÚ·ÊÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ (2,27). ªÂÙ¿ıÂÛË t(1;19)(q23;p13.3)/der (19) t(1;19) ∏ ¯ÚˆÌÔÛˆÌÈ΋ ÌÂÙ¿ıÂÛË t(1;19)(q23;p13.3) ·Ó¢ڛÛÎÂÙ·È ÛÙÔ 20-25% ÙˆÓ ·È‰ÈÒÓ Ì √§§ Î·È ÚÔ-µ ·ÓÔÛÔÊ·ÈÓfiÙ˘Ô Ì ¤ÎÊÚ·ÛË ÙÔ˘ ·ÓÙÈÁfiÓÔ˘ clg. ∂›Ó·È Ë ÈÔ Û˘¯Ó‹ ¯ÚˆÌÔÛˆÌÈ΋ ‰È·Ù·Ú·¯‹, Ë ÔÔ›· ‰È·ÈÛÙÒÓÂÙ·È Ì ÙȘ ÎÏ·ÛÈΤ˜ ΢ÙÙ·ÚÔÁÂÓÂÙÈΤ˜ ÌÂıfi‰Ô˘˜. ™ÙÔ 25% ·Ó¢ڛÛÎÂÙ·È ˆ˜ ÈÛÔ˙˘ÁÈṲ̂ÓË ÌÂÙ¿ıÂÛË t(1;19)(q23;p13.3), ÂÓÒ ÛÙÔ ˘fiÏÔÈÔ 75% ˘¿Ú¯ÂÈ ˆ˜ ÌË ÈÛÔ˙˘ÁÈṲ̂ÓË ÌÂÙ¿ıÂÛË, ‰ËÏ·‰‹ ÚfiÎÂÈÙ·È ÁÈ· der(19) t(1;19). ™Â ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ Â›Ó·È ‰˘Ó·ÙfiÓ ÔÈ ‚Ï¿ÛÙ˜ Ó· ÂÚȤ¯Ô˘Ó Î·È ÙȘ ‰‡Ô ÌÔÚʤ˜ Ù˘ ¯ÚˆÌÔÛˆÌÈ΋˜ ‰È·Ù·Ú·¯‹˜ (2,28). Œ¯ÂÈ ÛËÌ·Û›· Ó· ·Ó·ÊÂÚı› fiÙÈ Ë ÚfiÁÓˆÛË Ù˘ ÓfiÛÔ˘ ıˆÚÂ›Ù·È Î·Ï‡ÙÂÚË fiÙ·Ó Ë ·Ú·¿Óˆ ‰È·Ù·Ú·¯‹ ˘¿Ú¯ÂÈ ˆ˜ ÌË ÈÛÔ˙˘ÁÈṲ̂ÓË ÌÂÙ¿ıÂÛË (2,28,29). ™Â ÌÔÚÈ·Îfi Â›Â‰Ô ·fi ÙË ¯ÚˆÌÔÛˆÌÈ΋ ·˘Ù‹ ‰È·Ù·Ú·¯‹ ÚÔ·ÙÂÈ Û‡ÓÙËÍË ÙˆÓ ÁÔÓȉ›ˆÓ ∂2∞ Î·È PBXI. ∆Ô ÁÔÓ›‰ÈÔ ∂2∞ ‰ڿ˙ÂÙ·È ÛÙÔ ¯ÚˆÌfiۈ̷ ≠19 (19p 13.3) Î·È Îˆ‰ÈÎÔÔÈ› ÙÔ˘˜ ·Ú¿ÁÔÓÙ˜ ∂12 Î·È ∂47, ÔÈ ÔÔ›ÔÈ ÂÓÈÛ¯‡Ô˘Ó ÙË Û‡Ó‰ÂÛË ÙˆÓ ·ÓÔÛÔÛÊ·ÈÚÈÓÒÓ (Ig enhancer - binding factors E12, E47). ∆Ô ÁÔÓ›‰ÈÔ ƒµÃπ ‰ڿ˙ÂÙ·È ÛÙÔ ¯ÚˆÌfiۈ̷ ≠1 (1q 23) Î·È ¤¯ÂÈ ¿ÁÓˆÛÙË ‰Ú¿ÛË. In vitro ¤¯ÂÈ Ê·Ó› fiÙÈ ÙÔ ÚÔ˚fiÓ Û‡ÓÙË͢ ÙˆÓ ÁÔÓȉ›ˆÓ ·˘ÙÒÓ ¤¯ÂÈ ‰Ú¿ÛË ÔÁÎÔÁÔÓȉ›Ô˘, ÂÓÒ Ì ÌÔÚȷΤ˜ Ù¯ÓÈΤ˜ (reverse transcriptase polymerase chain reaction RT-PCR) Â›Ó·È ‰˘Ó·Ù‹ Ë ·Ó›¯Ó¢ÛË ÙÔ˘ ÁÔÓȉ›Ô˘ Û‡ÓÙË͢ ∂2∞-ƒµÃπ (2,30). ¶·È‰È·ÙÚÈ΋ 2008;71:263-270

Pediatri Jul-Aug 08

30-07-08

15:52

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∞. °·ÏÏ¿-µÔ˘Ì‚Ô˘Ú¿ÎË

¢ÔÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 11 (11q23) √È ‰ÔÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ Ì·ÎÚÔ‡ ÛΤÏÔ˘˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ≠11 (11q23) ·ÔÙÂÏÔ‡Ó Û¯ÂÙÈο Û˘¯Ófi ‡ÚËÌ·, ‰Â‰Ô̤ÓÔ˘ fiÙÈ ·Ú·ÙËÚÔ‡ÓÙ·È ÛÙÔ 60% ÙˆÓ ‚ÚÂÊÒÓ Ì √§§, Ì ËÏÈΛ· ÌÈÎÚfiÙÂÚË ÙˆÓ 12 ÌËÓÒÓ (2). ∞fi ÏÂ˘Ú¿˜ ÎÏÈÓÈ΋˜ ÚÔ‚ÔÏ‹˜ Ù˘ ÓfiÛÔ˘, Û¯ÂÙ›˙ÔÓÙ·È Ì ÌÂÁ¿ÏÔ ·ÚÈıÌfi Ï¢ÎÒÓ ·ÈÌÔÛÊ·ÈÚ›ˆÓ, ‰ÈfiÁΈÛË ‹·ÙÔ˜/ÛÏËÓfi˜, Û˘ÌÌÂÙÔ¯‹ ÙÔ˘ ∫¡™ Î·È ÚÔ-µ ·ÓÔÛÔÊ·ÈÓfiÙ˘Ô ÙˆÓ ‚Ï·ÛÙÒÓ (2,31). √È ‰ÔÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ ·ÊÔÚÔ‡Ó Î˘Ú›ˆ˜ ÌÂÙ·ı¤ÛÂȘ Î·È ÏÈÁfiÙÂÚÔ Û˘¯Ó¿ ÂÏÏ›ÌÌ·Ù· Î·È ·Ó·ÛÙÚÔʤ˜ Ù˘ ÂÚÈÔ¯‹˜ 11q23. √È Û˘¯ÓfiÙÂÚ˜ ¯ÚˆÌÔÛˆÌÈΤ˜ ÌÂÙ·ı¤ÛÂȘ Â›Ó·È Ë ÌÂÙ¿ıÂÛË t(4;11) Î·È Ë t(11;19), ÂÓÒ ÏÈÁfiÙÂÚÔ Û˘¯Ó¿ ·Ú·ÙËÚÔ‡ÓÙ·È ÔÈ ÌÂÙ·ı¤ÛÂȘ t(1;11), t(9;11) Î·È t(10;11) (31). √È ¯ÚˆÌÔÛˆÌÈΤ˜ ÌÂÙ·ı¤ÛÂȘ Ô˘ ·ÊÔÚÔ‡Ó ÙËÓ ÂÚÈÔ¯‹ ≠11q23 Û¯ÂÙ›˙ÔÓÙ·È Ì η΋ ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘, Û ·ÓÙ›ıÂÛË Ì ٷ ÂÏÏ›ÌÌ·Ù· Î·È ÙȘ ·Ó·ÛÙÚÔʤ˜ Ù˘ ÂÚÈÔ¯‹˜, fiÔ˘ Ë ÚfiÁÓˆÛË Ù˘ ÓfiÛÔ˘ Â›Ó·È Î·Ï‹ (2,31-33). ™Â ÌÔÚÈ·Îfi Â›‰Ô, ·fi ÙȘ ¯ÚˆÌÔÛˆÌÈΤ˜ ·˘Ù¤˜ ÌÂÙ·ı¤ÛÂȘ ÚÔηÏÂ›Ù·È ·Ó·‰È¿Ù·ÍË ÙÔ˘ ÁÔÓȉ›Ô˘ MLL (Mixed Lineage Leukemia) Ô˘ ‰ڿ˙ÂÙ·È ÛÙËÓ ÂÚÈÔ¯‹ q23 ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ≠11 Î·È Â›Ó·È ˘‡ı˘ÓÔ ÁÈ· ÙËÓ ·Ó¿Ù˘ÍË Ì˘ÂÏÔÁÂÓÔ‡˜/ÏÂÌÊÔÁÂÓÔ‡˜ Ï¢¯·ÈÌ›·˜. ÷ڷÎÙËÚÈÛÙÈÎfi ·Ú¿‰ÂÈÁÌ· Â›Ó·È Ë ÌÂÙ¿ıÂÛË t(4;11)(q21;q23), ÛÙËÓ ÔÔ›· Â¤Ú¯ÂÙ·È ·ÓÙÈ·Ú¿ıÂÛË ÙÔ˘ ÁÔÓȉ›Ô˘ MLL Ì ÙÔ ÁÔÓ›‰ÈÔ AF4 Ô˘ ‰ڿ˙ÂÙ·È ÛÙÔ ¯ÚˆÌfiۈ̷ ≠4 (q21) Î·È ıˆÚÂ›Ù·È Â›Û˘ ˘‡ı˘ÓÔ ÁÈ· ÙËÓ ÂÌÊ¿ÓÈÛË ÔÍ›·˜ Ï¢¯·ÈÌ›·˜ (2,31,33,34). ∞Í›˙ÂÈ Ó· ·Ó·ÊÂÚı› fiÙÈ ÙÔ ÁÔÓ›‰ÈÔ MLL ·ÔÙÂÏÂ›Ù·È ·fi 36 ÂÍfiÓÈ·, Έ‰ÈÎÔÔÈ› ÚˆÙ½ÓË 430 KD, Ë ÔÔ›· ÂÓÙÔ›˙ÂÙ·È ÙfiÛÔ ÛÙÔÓ ˘Ú‹Ó·, fiÛÔ Î·È ÛÙÔ Î˘ÙÙ·ÚfiÏ·ÛÌ·, ÂÎÊÚ¿˙ÂÙ·È Û ÔÈΛÏÔ˘˜ ÈÛÙÔ‡˜, fiˆ˜ ÛÙÔÓ ÂÁΤʷÏÔ, ÙÔ ı‡ÌÔ, ÙÔ ÛÏ‹Ó·, ÙÔ ‹·Ú, ÙËÓ Î·Ú‰È¿, ÙÔ˘˜ ÓÂÊÚÔ‡˜, ÙÔ ¤ÓÙÂÚÔ, ÙÔ˘˜ Ó‡ÌÔÓ˜, ÙÔ˘˜ fiÚ¯ÂȘ, ÙÔ ı˘ÚÂÔÂȉ‹ Î·È ÙȘ ·Ì˘Á‰·Ï¤˜, Î·È ·ÛΛ Ú˘ıÌÈÛÙÈ΋ ‰Ú¿ÛË ÛÙË ÌÂÙ·ÁÚ·Ê‹ (35). ∏ ·ÒÏÂÈ· Î·È ÙˆÓ ‰‡Ô ·ÏÏËÏfiÌÔÚÊˆÓ ÁÔÓȉ›ˆÓ MLL Â›Ó·È ·Û‡Ì‚·ÙË Ì ÙË ˙ˆ‹, ÂÓÒ Ë ‰È·Ù·Ú·¯‹ ÙÔ˘ ÂÓfi˜ ·ÏÏËÏfiÌÔÚÊÔ˘ ÚÔηÏ› ‰È·Ù·Ú·¯‹ ÛÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ ÁÔÓȉ›Ô˘, Ì ·ÔÙ¤ÏÂÛÌ· ·Ó·ÛÙÔÏ‹ Ù˘ ·Ó¿Ù˘Í˘, ·Ó·ÈÌ›·, ıÚÔÌ‚ÔÂÓ›·, ‰È·Ù·Ú·¯¤˜ ÙˆÓ µ-΢ÙÙ¿ÚˆÓ Î·È ÌÈÎÚfi ·ÚÈıÌfi ·ÔÈÎÈÒÓ ÙÔ˘ ·ÈÌÔÔÈËÙÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ (35). ∏ ·Ó·‰È¿Ù·ÍË ÙÔ˘ ÁÔÓȉ›Ô˘ MLL Â›Ó·È ‰˘Ó·Ùfi Ó· ·ÓȯÓ¢ı› Ì ÙËÓ Ù¯ÓÈ΋ ÙÔ˘ ÊıÔÚ›˙ÔÓÙ· in situ ˘‚ÚȉÈÛÌÔ‡ (FISH), ηıÒ˜ Î·È Ì ÌÔÚȷΤ˜ Ù¯ÓÈΤ˜ (reverse transcriptase polymerase chain reaction RT-PCR) (35). £ÂˆÚÂ›Ù·È Ì¿ÏÈÛÙ· ÂȂ‚ÏË̤ÓÔ Ó· Paediatriki 2008;71:263-270

ÚÔÛ‰ÈÔÚ›˙ÂÙ·È Â¿Ó ˘¿Ú¯ÂÈ ·Ó·‰È¿Ù·ÍË ÙÔ˘ ÁÔÓȉ›Ô˘ MLL ÛÙȘ ÂÚÈÙÒÛÂȘ Ô˘ ·Ó¢ڛÛÎÔÓÙ·È ¯ÚˆÌÔÛˆÌÈΤ˜ ‰È·Ù·Ú·¯¤˜, ÔÈ Ôԛ˜ ·ÊÔÚÔ‡Ó ÙËÓ ÂÚÈÔ¯‹ q23 ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ≠11, ÚÔÎÂÈ̤ÓÔ˘ Ó· ηıÔÚÈÛÙ› ÙÔ Â›‰Ô˜ Ù˘ ıÂÚ·¢ÙÈ΋˜ ·ÁˆÁ‹˜ Ô˘ ı· ·ÎÔÏÔ˘ıËı› ÛÙÔÓ ·ÛıÂÓ‹ (35). ÃÚˆÌfiۈ̷ ºÈÏ·‰¤ÏÊÂÈ·: t (9;22)(q34;q11.2) ∆Ô ¯ÚˆÌfiۈ̷ ºÈÏ·‰¤ÏÊÂÈ·, ‰ËÏ·‰‹ Ë ¯ÚˆÌÔÛˆÌÈ΋ ÌÂÙ¿ıÂÛË t(9;22)(q34;q11.2), ·Ú·ÙËÚÂ›Ù·È ÛÙÔ 3-5% ÙˆÓ ·È‰ÈÒÓ Ì √§§. ∞fi ÏÂ˘Ú¿˜ ÎÏÈÓÈ΋˜ ¤ÎÊÚ·Û˘ Ù˘ ÓfiÛÔ˘, Û¯ÂÙ›˙ÂÙ·È Ì ÌÂÁ·Ï‡ÙÂÚË ËÏÈΛ· ·È‰ÈÒÓ, ÌÂÁ¿ÏÔ ·ÚÈıÌfi Ï¢ÎÒÓ ·ÈÌÔÛÊ·ÈÚ›ˆÓ, ·˘ÍË̤ÓË Û˘¯ÓfiÙËÙ· ‚Ï·ÛÙÒÓ FAB-L2, µ-·ÓÔÛÔÊ·ÈÓfiÙ˘Ô, ηڢfiÙ˘Ô Ì „¢‰Ô‰ÈÏÔÂȉÈÛÌfi Î·È Ôχ η΋ ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘ (2,36). ¶Ú¤ÂÈ Ó· ·Ó·ÊÂÚı› fiÙÈ ÙÔ ¯ÚˆÌfiۈ̷ ºÈÏ·‰¤ÏÊÂÈ·, ÂÓÒ Î˘ÙÙ·ÚÔÁÂÓÂÙÈο ‰ÂÓ ‰È·Ê¤ÚÂÈ ·fi ÂΛÓÔ Ô˘ ·Ú·ÙËÚÂ›Ù·È ÛÙË ¯ÚfiÓÈ· Ì˘ÂÏÔÁÂÓ‹ Ï¢¯·ÈÌ›· (ê§), Û ÌÔÚÈ·Îfi Â›Â‰Ô ¤¯ÂÈ ‰È·ÊÔÚÂÙÈο ÛËÌ›· ÙÔÌ‹˜ ·fi ÂΛӷ Ù˘ ê§ Î·È ‰ÂÓ ·Ó¢ڛÛÎÂÙ·È Î·Ù¿ ÙÔ ÛÙ¿‰ÈÔ Ù˘ Ï‹ÚÔ˘˜ ‡ÊÂÛ˘ Ù˘ ÓfiÛÔ˘ (2,36-38). ™Â ÌÔÚÈ·Îfi Â›Â‰Ô ·fi ÙË ¯ÚˆÌÔÛˆÌÈ΋ ·˘Ù‹ ÌÂÙ¿ıÂÛË Â¤Ú¯ÂÙ·È Û‡ÓÙËÍË ÙˆÓ ÁÔÓȉ›ˆÓ bcr (¯Ú≠22) Î·È abl (¯Ú≠9), ÙÔ ÚÔ˚fiÓ ÌÂÙ·ÁÚ·Ê‹˜ Ù˘ ÔÔ›·˜ ·ÚÔ˘ÛÈ¿˙ÂÈ ·˘ÍË̤ÓË ‰Ú·ÛÙËÚÈfiÙËÙ· ÎÈÓ¿Û˘ Ù˘ Ù˘ÚÔÛ›Ó˘ Î·È ÂÓÔ¯ÔÔÈÂ›Ù·È ÁÈ· ÂÌÊ¿ÓÈÛË Ï¢¯·ÈÌ›·˜ (2,39,40). ¢ÔÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ≠6 √È ‰ÔÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ≠6 ÛÙÔ 85% ÙˆÓ ÂÚÈÙÒÛÂˆÓ ·ÊÔÚÔ‡Ó ÂÏÏ›ÌÌ·Ù· ÙÔ˘ Ì·ÎÚÔ‡ ÛΤÏÔ˘˜ (6q). ∞Ó¢ڛÛÎÔÓÙ·È ÛÙÔ 4-13% ÙˆÓ ·È‰ÈÒÓ Ì √§§ Î·È ‰ÂÓ Ê·›ÓÂÙ·È Ó· Û¯ÂÙ›˙ÔÓÙ·È Ì ÙȘ ÂΉËÏÒÛÂȘ Î·È ÙËÓ ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘ (2,41). ¢ÔÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ≠9 √È ‰ÔÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ≠9 ·ÊÔÚÔ‡Ó Î˘Ú›ˆ˜ ÂÏÏ›ÌÌ·Ù· ÙÔ˘ ‚Ú·¯¤Ô˜ ÛΤÏÔ˘˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ (9p) Î·È ·Ó¢ڛÛÎÔÓÙ·È ÛÙÔ 712% ÙˆÓ ·È‰ÈÒÓ Ì √§§. ∞fi ÏÂ˘Ú¿˜ ÎÏÈÓÈ΋˜ ¤ÎÊÚ·Û˘ Ù˘ ÓfiÛÔ˘, ÔÈ ¯ÚˆÌÔÛˆÌÈΤ˜ ·˘Ù¤˜ ‰È·Ù·Ú·¯¤˜ Û¯ÂÙ›˙ÔÓÙ·È Ì ÌÂÁ·Ï‡ÙÂÚË ËÏÈΛ· ·È‰ÈÒÓ, ÌÂÁ¿ÏÔ ·ÚÈıÌfi Ï¢ÎÒÓ ·ÈÌÔÛÊ·ÈÚ›ˆÓ, ‰ÈfiÁΈÛË ÏÂÌÊ·‰¤ÓˆÓ, Û˘ÌÌÂÙÔ¯‹ ÙÔ˘ ÌÂÛÔıˆÚ·Î›Ô˘, ÛÏËÓÔÌÂÁ·Ï›·, ∆-·ÓÔÛÔÊ·ÈÓfiÙ˘Ô, ηıÒ˜ Î·È ·˘ÍË̤ÓË Û˘¯ÓfiÙËÙ· ÂÍˆÌ˘ÂÏÈ΋˜ ˘ÔÙÚÔ‹˜ (42). ™Â ÌÔÚÈ·Îfi Â›‰Ô, ·Ú·ÙËÚÂ›Ù·È ¤ÏÏÂÈ„Ë ÙˆÓ ÁÔÓȉ›ˆÓ Ù˘ ÈÓÙÂÚÊÂÚfiÓ˘, ηıÒ˜ Î·È ¤ÏÏÂÈ„Ë ‹ ÌÂÙ¿ÏÏ·ÍË ÙˆÓ ÔÁÎÔηٷÛÙ·ÏÙÈÎÒÓ ÁÔÓȉ›ˆÓ MTS1 Î·È MTS2, Ù· ÔÔ›· ‰ڿ˙ÔÓÙ·È ÛÙÔ ‚Ú·¯‡ ÛΤÏÔ˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ≠9 (9p21-p22) (43,44).

Pediatri Jul-Aug 08

30-07-08

15:52

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267

°ÂÓÂÙÈ΋ Î·È Ï¢¯·ÈÌ›· ÛÙ· ·È‰È¿

ÃÚˆÌÔÛˆÌÈΤ˜ ÌÂÙ·ı¤ÛÂȘ t(8;14)/t(2;8)/t(8;22) √È ¯ÚˆÌÔÛˆÌÈΤ˜ ÌÂÙ·ı¤ÛÂȘ t(8;14), t(2;8), t(8;22), ÌÂ Û˘¯ÓfiÙÂÚË ÙË ÌÂÙ¿ıÂÛË t(8;14), ·Ó¢ڛÛÎÔÓÙ·È ÛÙÔ 3-5% ÙˆÓ ·È‰ÈÒÓ Ì √§§ Î·È ÛÙÔ 8590% ÙˆÓ ÂÚÈÙÒÛÂˆÓ √§§ ·fi µ-·ÙÙ·Ú· Ì ıÂÙÈÎfi ÙÔ ·ÓÙÈÁfiÓÔ slg (2). ™¯ÂÙ›˙ÔÓÙ·È Ì ۯÂÙÈο ηϋ ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘ (45). ™Â ÌÔÚÈ·Îfi Â›‰Ô, ·fi ÙȘ ÌÂÙ·ı¤ÛÂȘ ·˘Ù¤˜ ‰ËÌÈÔ˘ÚÁÂ›Ù·È Û‡ÓÙËÍË ÙÔ˘ ÚˆÙÔÔÁÎÔÁÔÓȉ›Ô˘ MYC (¯Ú≠8 q24.1) Ô˘ Â›Ó·È ÌÂÙ·ÁÚ·ÊÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ Î·È ÂÓ¤¯ÂÙ·È ÛÙË ‰È·ÊÔÚÔÔ›ËÛË ÙˆÓ Î˘ÙÙ¿ÚˆÓ Ì ٷ ÁÔÓ›‰È· Ù˘ ·ÓÔÛÔÛÊ·ÈÚ›Ó˘. ™˘ÁÎÂÎÚÈ̤ӷ, Â¤Ú¯ÂÙ·È Û‡ÓÙËÍË Â›Ù Ì ÙÔ ÁÔÓ›‰ÈÔ JGH (¯Ú≠14) Ô˘ Â›Ó·È ˘‡ı˘ÓÔ ÁÈ· ÙË Ì ‚·ÚÂÈ¿ ¿Ï˘ÛÔ Ù˘ ·ÓÔÛÔÛÊ·ÈÚ›Ó˘ ›Ù Ì ٷ ÁÔÓ›‰È· JGK (¯Ú≠2) ‹ JGI (¯Ú≠22) Ô˘ ¢ı‡ÓÔÓÙ·È ÁÈ· ÙËÓ ·Ú·ÁˆÁ‹ Ù˘ Î Î·È Ï ÂÏ·ÊÚ¿˜ ·Ï‡ÛÔ˘ Ù˘ ·ÓÔÛÔÛÊ·ÈÚ›Ó˘, ·ÓÙÈÛÙÔ›¯ˆ˜. ∆Ô ÙÂÏÈÎfi ·ÔÙ¤ÏÂÛÌ· Ù˘ Û‡ÓÙË͢ ÙˆÓ ÁÔÓȉ›ˆÓ ·˘ÙÒÓ Â›Ó·È Ë ‰˘ÛÏÂÈÙÔ˘ÚÁ›· Ù˘ ÌÂÙ·ÁÚ·ÊfiÌÂÓ˘ ÚˆÙ½Ó˘ (46,47). ÃÚˆÌÔÛˆÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÛÙËÓ √§§ ·fi ∆-ÏÂÌÊÔ·ÙÙ·Ú· ∏ √§§ ·fi ∆-ÏÂÌÊÔ·ÙÙ·Ú· ·ÔÙÂÏ› ÙÔ 15% Ù˘ √§§ Ù˘ ·È‰È΋˜ ËÏÈΛ·˜ Î·È ¤¯ÂÈ Î·Î‹ ÚfiÁÓˆÛË. ÃÚˆÌÔÛˆÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÛÙÔ˘˜ ‚Ï¿ÛÙ˜ ·Ó¢ڛÛÎÔÓÙ·È Û Ôχ ÌÈÎÚfi ·ÚÈıÌfi ·ÛıÂÓÒÓ, Â›Ó·È Î˘Ú›ˆ˜ ÙÔ˘ Ù‡Ô˘ ÙˆÓ ¯ÚˆÌÔÛˆÌÈÎÒÓ ÌÂÙ·ı¤ÛˆÓ, ÂÓÒ ‰ÂÓ ˘¿Ú¯ÂÈ ÔÏ˘ÏÔÂȉÈÛÌfi˜ (48,49). ∆· ¯ÚˆÌÔÛÒÌ·Ù· ÛÙ· ÔÔ›· ·Ú·ÙËÚÔ‡ÓÙ·È ‰È·Ù·Ú·¯¤˜ Â›Ó·È Î˘Ú›ˆ˜ ÙÔ Ì·ÎÚfi ÛΤÏÔ˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ≠14 (14q), ηıÒ˜ Î·È ÙÔ ‚Ú·¯‡ ‹ Ì·ÎÚfi ÛΤÏÔ˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ≠7 (7p ‹ 7q), ÛÙ· ÔÔ›· ÂÓÙÔ›˙ÔÓÙ·È Ù· ˘‡ı˘Ó· ÁÔÓ›‰È· ÁÈ· ÙÔ˘˜ ˘ԉԯ›˜ ÙˆÓ ∆-ÏÂÌÊÔ΢ÙÙ¿ÚˆÓ (TCR genes) (49,50). √È ¯ÚˆÌÔÛˆÌÈΤ˜ ÌÂÙ·ı¤ÛÂȘ Ô˘ ¤¯Ô˘Ó ·Ú·ÙËÚËı› ÛÙËÓ √§§ ·fi ∆-ÏÂÌÊÔ·ÙÙ·Ú· Â›Ó·È Î·Ù¿ ÛÂÈÚ¿ Û˘¯ÓfiÙËÙ·˜: t(11;14)(p13;q11.2), t(10;14) (q24;q11.2), t(1;14)(p32-p34; q11.2), t(8;14)(q24.1; q11.2), ηıÒ˜ Î·È ÔÈ ÌÂÙ·ı¤ÛÂȘ t(7;9)(q35;q32) Î·È t(7;11)(q35;p13) (51-54).

√Í›· Ì˘ÂÏÔÁÂÓ‹˜ Ï¢¯·ÈÌ›· ∏ ÔÍ›· Ì˘ÂÏÔÁÂÓ‹˜ Ï¢¯·ÈÌ›· (√ª§) ·ÔÙÂÏ› ÙÔ 15-20% Ù˘ ÔÍ›·˜ Ï¢¯·ÈÌ›·˜ Ù˘ ·È‰È΋˜ ËÏÈΛ·˜ Î·È ÙÔ 25% Ù˘ Ï¢¯·ÈÌ›·˜ ÙÔ˘ ÚÒÙÔ˘ ¯ÚfiÓÔ˘ ˙ˆ‹˜. ∆· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· Ë ÚfiÁÓˆÛË Ù˘ ÓfiÛÔ˘ ¤¯ÂÈ Û·ÊÒ˜ ‚ÂÏÙȈı› Ì ÙȘ Ӥ˜ ıÂÚ·¢ÙÈΤ˜ ÚÔÛÂÁÁ›ÛÂȘ, ÔÈ Ôԛ˜ fï˜ ‰ÂÓ ÛÙÂÚÔ‡ÓÙ·È ÂÈÏÔÎÒÓ (35,44). ∞Í›˙ÂÈ Ó· ·Ó·ÊÂÚı› fiÙÈ √ª§ ·Ó·Ù‡ÛÛÂÙ·È ÌÂ

¶›Ó·Î·˜ 3. ÃÚˆÌÔÛˆÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÛÙËÓ √ª§ ¢È·Ù·Ú·¯‹

ÃÚˆÌfiۈ̷

ªÂÙ¿ıÂÛË

t(8;21) t(15;17) inv(16) t(16;16) t(11q-) t(6;9) t(9;22)

∆ÚÈۈ̛·

≠8 ≠11

∂ÏÏ›ÌÌ·Ù·

12p 5q 7q 9q 3 (p, q)

™‡ÓıÂÙÔÈ Î·Ú˘fiÙ˘ÔÈ

·˘ÍË̤ÓË Û˘¯ÓfiÙËÙ· Û ·È‰È¿ Ì ÙÚÈۈ̛· 21, ·Ï·ÛÙÈ΋ ·Ó·ÈÌ›· Fanconi, Û‡Ó‰ÚÔÌÔ Bloom, Kostmann ‹ Û‡Ó‰ÚÔÌÔ Blackfan-Diamond. ∂›Û˘, Â›Ó·È ÁÓˆÛÙfi fiÙÈ √ª§ ·ÚÔ˘ÛÈ¿˙ÂÙ·È Ì ·˘ÍË̤ÓË Û˘¯ÓfiÙËÙ· Û ·ÛıÂÓ›˜ Ô˘ ¤¯Ô˘Ó ˘Ô‚ÏËı› Û ·ÎÙÈÓÔıÂÚ·›· ‹ ¯ËÌÂÈÔıÂÚ·›· Ì ·Ï΢ÏÈÔ‡ÓÙ˜ ·Ú¿ÁÔÓÙ˜ (55).

ÃÚˆÌÔÛˆÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÛÙËÓ √ª§ ÃÚˆÌÔÛˆÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ ·Ú·ÙËÚÔ‡ÓÙ·È ÛÙÔ 50-80% ÙˆÓ ·ÛıÂÓÒÓ Ì √ª§, ÔÈ Î˘ÚÈfiÙÂÚ˜ ·fi ÙȘ Ôԛ˜ ·Ó·Ê¤ÚÔÓÙ·È ÛÙÔÓ ¶›Ó·Î· 3. √È Û˘¯ÓfiÙÂÚ˜ ¯ÚˆÌÔÛˆÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ Â›Ó·È ÔÈ ÌÂÙ·ı¤ÛÂȘ t(8;21), t(15;17), inv(16)/t(16;16), ηıÒ˜ Î·È ÌÂÙ·ı¤ÛÂȘ Ô˘ ·ÊÔÚÔ‡Ó ÙÔ Ì·ÎÚfi ÛΤÏÔ˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ≠11 [t(11q-)] ÔÈ Ôԛ˜ Î·È ·ÔÙÂÏÔ‡Ó ÙÔ 3547% ÙˆÓ ‰È·Ù·Ú·¯ÒÓ Ô˘ ·Ú·ÙËÚÔ‡ÓÙ·È ÛÙËÓ √ª§ Î·È ¤¯Ô˘Ó ȉȷ›ÙÂÚË ÚÔÁÓˆÛÙÈ΋ ·Í›· (50,55). ∂›Û˘, ·Ó¢ڛÛÎÔÓÙ·È ÙÚÈۈ̛˜ ΢ڛˆ˜ ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ≠8 Î·È ≠11, ηıÒ˜ Î·È ¯ÚˆÌÔÛˆÌÈο ÂÏÏ›ÌÌ·Ù· ÙÔ˘ ‚Ú·¯¤Ô˜ ÛΤÏÔ˘˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ≠12 (12p) Î·È ÙÔ˘ Ì·ÎÚÔ‡ ÛΤÏÔ˘˜ ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ≠5 (5q), ≠7 (7q) Î·È ≠9 (9q) (50). ∆¤ÏÔ˜, Â›Ó·È ‰˘Ó·Ùfi Ó· ·Ú·ÙËÚËıÔ‡Ó Î·È “Û‡ÓıÂÙÔÈ” ηڢfiÙ˘ÔÈ Ì ÙÚÂȘ ‹ ÂÚÈÛÛfiÙÂÚ˜ ¯ÚˆÌÔÛˆÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ (56). ∞fi ÌÂϤÙ˜ ¤¯ÂÈ Ê·Ó› fiÙÈ Ë ÂÓÙ·ÂÙ‹˜ ÂÈ‚›ˆÛË ÙˆÓ ·ÛıÂÓÒÓ Ì √ª§ ÂÍ·ÚÙ¿Ù·È ·fi Ù· ΢ÙÙ·ÚÔÁÂÓÂÙÈο Â˘Ú‹Ì·Ù·. ∞Ó·Ï˘ÙÈÎfiÙÂÚ·, ÔÈ ·ÛıÂÓ›˜ ÌÂ Ê˘ÛÈÔÏÔÁÈÎfi ηڢfiÙ˘Ô ‹ Ì ÙȘ ¯ÚˆÌÔÛˆÌÈΤ˜ ÌÂÙ·ı¤ÛÂȘ t(8;21), t(15;17), t(16;16) ¤¯Ô˘Ó ηϋ ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘ (55,56). ∞ÓÙ›ıÂÙ· ÔÈ ·ÛıÂÓ›˜ Ì “Û‡ÓıÂÙÔ˘˜” ηڢfiÙ˘Ô˘˜ ‹ ÂÏÏ›ÌÌ·Ù· ÛÙÔ Ì·ÎÚfi ¶·È‰È·ÙÚÈ΋ 2008;71:263-270

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ÛΤÏÔ˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ≠5 (5q) ‹ ≠7 (7q), ÂÏÏ›ÌÌ·Ù· ‹ ·Ó·ÛÙÚÔʤ˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ≠3, ÌÂÙ¿ıÂÛË t(6;9), ‰ÔÌÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ≠11 (11q23) ‹ ¯ÚˆÌfiۈ̷ ºÈÏ·‰¤ÏÊÂÈ· ¤¯Ô˘Ó η΋ ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘ (55,56). ªÂÙ¿ıÂÛË t(8;21)(q22; q22) ∏ ÌÂÙ¿ıÂÛË t(8;21)(q22; q22) ·Ú·ÙËÚÂ›Ù·È Î˘Ú›ˆ˜ Û ÌÂÁ·Ï‡ÙÂÚ· ·È‰È¿ ÌÂ Ì˘ÂÏÔ‚Ï·ÛÙÈ΋ Ï¢¯·ÈÌ›· Î·È ¤ÎÊÚ·ÛË ÙˆÓ ·ÓÙÈÁfiÓˆÓ CD19 Î·È CD34 Î·È Û¯ÂÙ›˙ÂÙ·È Ì ̤ÙÚÈ· ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘ (55,56). ™Â ÌÔÚÈ·Îfi Â›Â‰Ô ·fi ÙË ÌÂÙ¿ıÂÛË Â¤Ú¯ÂÙ·È Û‡ÓÙËÍË ÙˆÓ ÁÔÓȉ›ˆÓ ∂∆√ (¯Ú≠8) Î·È AML1 (¯Ú≠21). Àfi Ê˘ÛÈÔÏÔÁÈΤ˜ Û˘Óı‹Î˜, ÙÔ ÁÔÓ›‰ÈÔ ∂∆√ Ú˘ıÌ›˙ÂÈ ÙË ‰È·ÊÔÚÔÔ›ËÛË ÙˆÓ Ì˘ÂÏÈÎÒÓ Î˘ÙÙ¿ÚˆÓ, ÂÓÒ ÙÔ ÁÔÓ›‰ÈÔ AML1 ·ÔÙÂÏ› ÌÂÙ·ÁÚ·ÊÈÎfi ·Ú¿ÁÔÓÙ·. ∏ ÚˆÙ½ÓË ÌÂÙ·ÁÚ·Ê‹˜ ÙÔ˘ ÁÔÓȉ›Ô˘ Û‡ÓÙË͢ AML1-∂∆√ ıˆÚÂ›Ù·È fiÙÈ ¤¯ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙËÓ ÂÌÊ¿ÓÈÛË Ù˘ √ª§ (55,56). ªÂÙ¿ıÂÛË t(15;17)(q22; q21) ∏ ÌÂÙ¿ıÂÛË t(15;17)(q22; q21) ·Ú·ÙËÚÂ›Ù·È Î˘Ú›ˆ˜ Û ÌÂÁ·Ï‡ÙÂÚ· ·È‰È¿ Ì ÚÔÌ˘ÂÏÔ΢ÙÙ·ÚÈ΋ Ï¢¯·ÈÌ›· Ì ·ÒÏÂÈ· ÙÔ˘ HLA-DR Î·È Û¯ÂÙ›˙ÂÙ·È Ì ηϋ ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘ (55). ∏ ÌÂÙ¿ıÂÛË ·˘Ù‹ Û˘Ó·ÓÙ¿Ù·È Û˘¯Ó¿ Ì·˙› Ì ·ÒÏÂÈ· ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ ÙÔ˘ ʇÏÔ˘. ™˘ÁÎÂÎÚÈ̤ӷ, ÛÙÔ 39% ÙˆÓ ÂÚÈÙÒÛÂˆÓ ˘¿Ú¯ÂÈ ·ÒÏÂÈ· ÙÔ˘ ¯ÚˆÌ≠À ÂÓÒ ÛÙÔ 10% ·Ú·ÙËÚÂ›Ù·È ¤ÏÏÂÈ„Ë ÙÔ˘ ¯ÚˆÌ≠Ã. ™Â ÌÔÚÈ·Îfi Â›‰Ô, ·fi ÙË ÌÂÙ¿ıÂÛË Â¤Ú¯ÂÙ·È Û‡ÓÙËÍË ÙˆÓ ÁÔÓȉ›ˆÓ PML Î·È RAR. ∆Ô ÁÔÓ›‰ÈÔ PML (¯Ú≠15) Â›Ó·È ÙÔ ˘‡ı˘ÓÔ ÁÔÓ›‰ÈÔ ÁÈ· ÙËÓ ÚÔÌ˘ÂÏÔ΢ÙÙ·ÚÈ΋ Ï¢¯·ÈÌ›·, ÂÓÒ ÙÔ ÁÔÓ›‰ÈÔ RAR (¯Ú≠17) Â›Ó·È ÙÔ ˘‡ı˘ÓÔ ÁÔÓ›‰ÈÔ ÁÈ· ÙÔÓ · ˘Ô‰Ô¯¤· ÙÔ˘ ÚÂÙÈÓÔ˚ÎÔ‡ ÔͤԘ. ∏ Û‡ÓÙËÍË ÙˆÓ ÁÔÓȉ›ˆÓ ·˘ÙÒÓ ÂÈʤÚÂÈ ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÙÔ˘ ˘Ô‰Ô¯¤· ÙÔ˘ ÚÂÙÈÓÔ˚ÎÔ‡ ÔͤԘ, ·‰˘Ó·Ì›· ÙÔ˘ ΢ÎÏÔÊÔÚÔ‡ÓÙÔ˜ ÚÂÙÈÓÔ˚ÎÔ‡ ÔͤԘ Ó· ÂÓÂÚÁÔÔÈ‹ÛÂÈ Ê˘ÛÈÔÏÔÁÈο ÁÔÓ›‰È·-ÛÙfi¯Ô˘˜, Ì ÙÂÏÈÎfi ·ÔÙ¤ÏÂÛÌ· ÙË ‰È·ÎÔ‹ Ù˘ ÌÂÙ·ÁÚ·Ê‹˜ Î·È Ù˘ ‰È·ÊÔÚÔÔ›ËÛ˘ ÙˆÓ Î˘ÙÙ¿ÚˆÓ (55). ∞Ó·ÛÙÚÔÊ‹/ÌÂÙ¿ıÂÛË ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ ≠16 inv(16)/t(16;16) ∏ ·Ó·ÛÙÚÔÊ‹ inv(16)(p 13q22) Î·È Ë ÌÂÙ¿ıÂÛË t(16;16)(p13;q22) ·Ú·ÙËÚÔ‡ÓÙ·È Î˘Ú›ˆ˜ Û ÌÂÁ·Ï‡ÙÂÚ· ·È‰È¿ ÌÂ Ì˘ÂÏÔÌÔÓÔ΢ÙÙ·ÚÈ΋ Ï¢¯·ÈÌ›· Ì ˈÛÈÓÔÊÈÏ›· Î·È Û¯ÂÙ›˙ÔÓÙ·È Ì ηϋ ¤Î‚·ÛË Ù˘ ÓfiÛÔ˘. ™Â ÌÔÚÈ·Îfi Â›‰Ô, ·fi ÙȘ ¯ÚˆÌÔÛˆÌÈΤ˜ ·˘Ù¤˜ ·Ó·Î·Ù·Ù¿ÍÂȘ Â¤Ú¯ÂÙ·È Û‡ÓÙËÍË ÙˆÓ ÁÔÓȉ›ˆÓ CBFbeta Î·È ªÀ∏11 Ô˘ ‰ڿ˙ÔÓÙ·È ÛÙÔ ¯ÚˆÌfiۈ̷ ≠16 (55,56). ™Â Ê˘ÛÈÔÏÔÁÈΤ˜ Û˘Óı‹Î˜, ÙÔ ÁÔÓ›Paediatriki 2008;71:263-270

‰ÈÔ CBFbeta Έ‰ÈÎÔÔÈ› ˘ÔÔÌ¿‰· ÙÔ˘ ·Ú¿ÁÔÓÙ· Û‡Ó‰ÂÛ˘ Ì ÙÔÓ ˘Ú‹Ó· (Core Binding Factor CBF), ÂÓÒ ÙÔ ÁÔÓ›‰ÈÔ ªÀ∏11 Έ‰ÈÎÔÔÈ› ÌÈ· ÌÔÚÊ‹ Ù˘ ‚·ÚÂÈ¿˜ ·Ï‡ÛÔ˘ Ù˘ Ì˘ÔÛ›Ó˘ ÙˆÓ Ï›ˆÓ Ì˘˚ÎÒÓ ÈÓÒÓ (50,55). √ Ì˯·ÓÈÛÌfi˜ Ì ÙÔÓ ÔÔ›Ô ÚÔηÏÂ›Ù·È Ë Ï¢¯·ÈÌ›· ·fi ÙÔ ÁÔÓ›‰ÈÔ Û‡ÓÙË͢ CBFbeta-MYH11 ‰ÂÓ Â›Ó·È ÁÓˆÛÙfi˜. £ÂˆÚÂ›Ù·È fï˜ fiÙÈ Ë ÚˆÙ½ÓË Û‡ÓÙË͢ ›Ù ÂÌÔ‰›˙ÂÈ ÙËÓ ÂÓÂÚÁÔÔ›ËÛË ··Ú·›ÙËÙˆÓ ÁÔÓȉ›ˆÓ Ù˘ ·ÈÌÔÔ›ËÛ˘ ›Ù “·ÏÏÔÈÒÓÂÈ” ÌÂÙ·ÁÚ·ÊÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ Û ÁÂÈÙÔÓÈΤ˜ ı¤ÛÂȘ, Ì ·ÔÙ¤ÏÂÛÌ· ÙË ‰˘ÛÏÂÈÙÔ˘ÚÁ›· Ù˘ Ê˘ÛÈÔÏÔÁÈ΋˜ ‰È·ÊÔÚÔÔ›ËÛ˘ ÙˆÓ ·ÈÌÔÔÈËÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ (55,56).

ªÂÏÏÔÓÙÈÎÔ› ÛÙfi¯ÔÈ ªÂ ÙË Û˘Ó¯‹ ÂͤÏÈÍË Ù˘ ÌÔÚȷ΋˜ ‚ÈÔÏÔÁ›·˜, Â›Ó·È ‰˘Ó·Ùfi Ó· ·ÓȯÓ¢ıÔ‡Ó Ì ÌÔÚȷΤ˜ Ù¯ÓÈΤ˜ ÔÈ ÚˆÙ½Ó˜ ÌÂÙ·ÁÚ·Ê‹˜ ÙˆÓ ÁÔÓȉ›ˆÓ Û‡ÓÙË͢, Ô˘ Â›Ó·È ·ÔÙ¤ÏÂÛÌ· ÙˆÓ ÚÔ·Ó·ÊÂÚı¤ÓÙˆÓ ¯ÚˆÌÔÛˆÌÈÎÒÓ ‰È·Ù·Ú·¯ÒÓ. √ ÛÙfi¯Ô˜ Â›Ó·È ÔÈ ÚˆÙ½Ó˜ ·˘Ù¤˜ Ó· ¯ÚËÛÈÌÔÔÈËıÔ‡Ó ˆ˜ ‰Â›ÎÙ˜ ÁÈ· ÙËÓ ·Ó‡ÚÂÛË Î·È ÙËÓ ·Ú·ÎÔÏÔ‡ıËÛË Ù˘ Ù˘¯fiÓ ˘ÔÏÂÈfiÌÂÓ˘ ÓfiÛÔ˘ (Minimal Residual Disease) ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì ·ÈÌ·ÙÔÏÔÁÈΤ˜ ηÎÔ‹ıÂȘ. ªÂ Ù· ̤¯ÚÈ ÙÒÚ· ‰Â‰Ô̤ӷ, ·˘Ùfi ‰ÂÓ Â›Ó·È ÂÊÈÎÙfi, ‰ÈfiÙÈ ·ÚfiÌÔÈ· ÚÔ˚fiÓÙ· ÌÂÙ·ÁÚ·Ê‹˜ ÁÔÓȉ›ˆÓ ¤¯Ô˘Ó ·ÓÂÚ¢ı› Î·È ÛÙÔ ·›Ì· Î·È ÛÙÔ Ì˘ÂÏfi ÙˆÓ ÔÛÙÒÓ ˘ÁÈÒÓ ·ÙfïÓ. √È ‰È·ÊÔÚ¤˜ fï˜ Â›Ó·È ÛËÌ·ÓÙÈΤ˜ Î·È ·ÊÔÚÔ‡Ó ÙÔ Ì‹ÎÔ˜ Î·È ÙËÓ ·ÏÏËÏÔ˘¯›· ÙˆÓ ÚÔ˚fiÓÙˆÓ ÌÂÙ·ÁÚ·Ê‹˜ ÙˆÓ ÁÔÓȉ›ˆÓ Û‡ÓÙË͢, fiˆ˜ .¯. ÙÔ˘ ÁÔÓȉ›Ô˘ AML1-ETO ÛÙÔ˘˜ ¿Û¯ÔÓÙ˜ ·fi Ï¢¯·ÈÌ›· ·’ fi,ÙÈ ÛÙ· ˘ÁÈ‹ ¿ÙÔÌ·. ™‹ÌÂÚ·, ·ÚÎÂÙ¤˜ ÌÂϤÙ˜ ‚Ú›ÛÎÔÓÙ·È Û ÂͤÏÈÍË, ÚÔÎÂÈ̤ÓÔ˘ ÔÈ ÌÔÚÈ·ÎÔ› ·˘ÙÔ› ‰Â›ÎÙ˜ Ó· Ù·˘ÙÔÔÈËıÔ‡Ó, ÒÛÙ ӷ ¯ÚËÛÈÌÔÔÈËıÔ‡Ó ÛÙÔ Ì¤ÏÏÔÓ ÛÙËÓ Î·ıËÌÂÚÈÓ‹ È·ÙÚÈ΋ Ú¿ÍË (2,18). µÈ‚ÏÈÔÁÚ·Ê›· 1. Crist N, Pui CH. The Leukemias. In: Nelson W, Behrman R, Kliegman R, Arvin A, editors. Textbook of Paediatrics.

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ªË Ù˘¯·›· ·‰Ú·ÓÔÔ›ËÛË ÙÔ˘ ÃÚˆÌÔÛÒÌ·ÙÔ˜ Ã: ÎÏÈÓÈΤ˜ ÂÈÙÒÛÂȘ ÙÔ˘ Ê·ÈÓÔ̤ÓÔ˘ skewing ÛÙ· ·È‰È¿ Î·È ÙÔ˘˜ ÂÓ‹ÏÈΘ °. §·‚Ú¿ÓÔ˜, ƒ. ∞ÁÁÂÏÔÔ‡ÏÔ˘ ¶ÂÚ›ÏË„Ë: ∏ ·‰Ú·ÓÔÔ›ËÛË ÙÔ˘ ÃÚˆÌÔÛÒÌ·ÙÔ˜ Ã Â›Ó·È Ê·ÈÓfiÌÂÓÔ Ê˘ÛÈÔÏÔÁÈÎfi Î·È Û˘Ó›ÛÙ·Ù·È ÛÙË ÌÂÙ·ÁÚ·ÊÈ΋ ηٷÛÙÔÏ‹ ÙÔ˘ Û˘ÓfiÏÔ˘ ۯ‰fiÓ ÙˆÓ ÁÔÓȉ›ˆÓ fiÏˆÓ ÙˆÓ ¯ÚˆÌÔÛˆÌ¿ÙˆÓ Ã, ÏËÓ ÂÓfi˜ Û ¤Ì‚Ú˘· ıËÏ·ÛÙÈÎÒÓ, ÒÛÙ ӷ ‰È·ÙËÚÂ›Ù·È ÂÓÂÚÁfi ÌfiÓÔ ¤Ó· ·ÓÙ›ÁÚ·ÊÔ Î¿ı ÁÔÓȉ›Ô˘ ·Ó¿ ·ÙÙ·ÚÔ. ∏ ‰È·‰Èηۛ· ·˘Ù‹ ‰È·ÙËÚÂ›Ù·È ÛÙ·ıÂÚ¿ Û fiÏ· Ù· ‰ÈÏÔÂȉÈο ·ÙÙ·Ú· ÙÔ˘ ÂÓ‹ÏÈη ÔÚÁ·ÓÈÛÌÔ‡ Î·È ·ÊÔÚ¿ ÙfiÛÔ Ê˘ÛÈÔÏÔÁÈο ı‹Ï· ¿ÙÔÌ· Ì ηڢfiÙ˘Ô 46,Ãà (1 ·‰Ú·Ó¤˜ Ã), fiÛÔ Î·È ¿ÙÔÌ· Ì ·ÚÈıÌËÙÈΤ˜/ÔÛÔÙÈΤ˜ ¯ÚˆÌÔÛˆÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÙˆÓ Ê˘ÏÂÙÈÎÒÓ ¯ÚˆÌÔۈ̿وÓ. ™ÙÔÓ ¿ÓıÚˆÔ, Û ·ÓÙ›ıÂÛË Ì ٷ ÌÔÓfiÙÚËÌ·, Ù· Ì·ÚÛÈÔÊfiÚ· Î·È Ù· ÙÚˆÎÙÈο ıËÏ·ÛÙÈο, Ë ÂÈÏÔÁ‹ ÙÔ˘ à ¯ÚˆÌÔÛÒÌ·ÙÔ˜ Ô˘ ˘fiÎÂÈÙ·È Û ·‰Ú·ÓÔÔ›ËÛË Á›ÓÂÙ·È Ù˘¯·›·, ÒÛÙ ӷ Â›Ó·È ‰È·ÊÔÚÂÙÈÎfi ¯ÚˆÌfiۈ̷ ÂÓÂÚÁfi Û οı ΢ÙÙ·ÚÈÎfi ÎÏÒÓÔ Ô˘ ÚÔ¤Ú¯ÂÙ·È ·fi ‰È·ÊÔÚÂÙÈÎfi ‚Ï·ÛÙÔÌÂÚ›‰ÈÔ ÙÔ˘ ÂÌ‚Ú‡Ô˘. ŒÙÛÈ, Ù· ¿ÙÔÌ· ηı›ÛÙ·ÓÙ·È ÏÂÈÙÔ˘ÚÁÈο ̈۷˚ο, Ì ·ÔÙ¤ÏÂÛÌ·, Û ÂÚ›ÙˆÛË ‰È·ÊÔÚÒÓ ÛÙ· ·ÏÏËÏfiÌÔÚÊ· ÙˆÓ Ã ¯ÚˆÌÔۈ̿وÓ, ·ÊÂÓfi˜ Ó· ÚÔÛٷهÔÓÙ·È ·fi ÙËÓ ¤ÎÊÚ·ÛË ·ıÔÏÔÁÈÎÒÓ ÁÔÓȉ›ˆÓ Î·È ·ÊÂÙ¤ÚÔ˘ Ó· ·˘Í¿ÓÂÙ·È Ë ‚ÈÔÔÈÎÈÏfiÙËÙ·, Ì ÙË ‰ËÌÈÔ˘ÚÁ›· ÂӉȿÌÂÛˆÓ Ê·ÈÓÔÙ‡ˆÓ ÏfiÁˆ Û˘ÓÂÈÎÚ¿ÙÂÈ·˜. ™Â ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ fï˜, ÁÈ· ¿ÁÓˆÛÙÔ ÏfiÁÔ, Ë ·‰Ú·ÓÔÔ›ËÛË ‰ÂÓ ·ÎÔÏÔ˘ı› ÙÔ Ù˘¯·›Ô ÚfiÙ˘Ô, Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ˘ÂÚÔ¯‹ ¤ÎÊÚ·Û˘ ÂÓfi˜ ·ÏÏËÏÔÌfiÚÊÔ˘. ∆¤ÙÔÈ· ÂÚÈÛÙ·ÙÈο ¤¯Ô˘Ó Û˘Ó‰Âı› Ì ÔÈΛϘ ÎÏÈÓÈΤ˜ ÂΉËÏÒÛÂȘ, fiˆ˜ ‰È¿ÊÔÚ· ÁÂÓÂÙÈο Û‡Ó‰ÚÔÌ·, ÔÏÏ·Ϥ˜ ·Ô‚ÔϤ˜, Û˘ÁÁÂÓ›˜ ·ÓÔÛÔ·ÓÂ¿ÚÎÂȘ Î·È ·˘ÙÔ¿ÓÔÛ· ÓÔÛ‹Ì·Ù·. ™ÙËÓ ·ÚÔ‡Û· ·Ó·ÛÎfiËÛË ·Ó·Ê¤ÚÔÓÙ·È ÓÂÒÙÂÚ· ‰Â‰Ô̤ӷ ÁÈ· ÙȘ Û˘Û¯ÂÙ›ÛÂȘ ·˘Ù¤˜ Î·È ÙËÓ Èı·Ó‹ ÙÔ˘˜ ·ÍÈÔÏfiÁËÛË, ÛÙÔ Ï·›ÛÈÔ Ù˘ ÎÏÈÓÈ΋˜ ÁÂÓÂÙÈ΋˜.

∂ÚÁ·ÛÙ‹ÚÈÔ πÛÙÔÏÔÁ›·˜∂Ì‚Ú˘ÔÏÔÁ›·˜, π·ÙÚÈ΋ ™¯ÔÏ‹ ∂ıÓÈÎÔ‡ ∫·Ô‰ÈÛÙÚÈ·ÎÔ‡ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ AÏÏËÏÔÁÚ·Ê›·: ƒˆÍ¿ÓË ∞ÁÁÂÏÔÔ‡ÏÔ˘ rangelop@med.uoa.gr ∂ÚÁ·ÛÙ‹ÚÈÔ πÛÙÔÏÔÁ›·˜∂Ì‚Ú˘ÔÏÔÁ›·˜, π·ÙÚÈ΋ ™¯ÔÏ‹ ∂ıÓÈÎÔ‡ ∫·Ô‰ÈÛÙÚÈ·ÎÔ‡ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ ∆.∫. 115 27, °Ô˘‰‹, ∞ı‹Ó·

§¤ÍÂȘ ÎÏÂȉȿ: AÓÙÈÛÙ¿ıÌÈÛË ‰fiÛ˘, ·‰Ú·ÓÔÔ›ËÛË ¯ÚˆÌÔÛÒÌ·ÙÔ˜ Ã, ÎÏÈÓÈ΋ ÁÂÓÂÙÈ΋.

Non-random X inactivation: clinical consequences of the skewing effect G. Lavranos, R. Angelopoulou Abstract: X chromosome inactivation is a normal genetic phenomenon, causing the transcriptional silencing of almost every gene located on all X chromosomes but one in mammalian embryos, so that only a single gene copy remains active per cell. This procedure remains stable in all the diploid cells of the adult organism and applies to both normal females with karyotype 46,XX (1 inactive X) and individuals with numerical/quantitative chromosomal abnormalitites of the gonosomes. In humans, contrary to monotremes, marsupials and rodent mammals, the selection of the X chromosome to be inactivated is made in random order, so that a different chromosome is active in each cell deriving from a different blastomere of the embryo. Thus, affected individuals may be viewed as functional mosaics, which results both in their protection from the expression of pathological/mutated alleles and in an increase of biodiversity, in cases of differences in X chromosome alleles, with the creation of new, intermediate phenotypes due to co-dominance. In certain cases, however, for a yet unknown reason, X chromosome inactivation does not conform to the random pattern associated with favourable expression of a specific allele. Such incidents have been associated with a variety of clinical manifestations, including several genetic syndromes, recurrent spontaneous abortion, congenital immune deficiencies and autoimmune disorders. In this review, novel data on these alleged correlations are discussed, along with guidelines on their evaluation within the context of clinical genetics.

Laboratory of HistologyEmbryology, Faculty of Medicine, National and Kapodistrian University of Athens Correspondence: Roxani Angelopoulou rangelop@med.uoa.gr Laboratory of HistologyEmbryology, Faculty of Medicine, National and Kapodistrian University of Athens 115 27, Goudi, Athens, Greece

Key words: Genetic dosage compensation, X chromosome inactivation, clinical genetics.

∂ÈÛ·ÁˆÁ‹ ∏ ·‰Ú·ÓÔÔ›ËÛË ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ Ã Â›Ó·È ÌÈ· ‰È·‰Èηۛ· ÌÂÙ·ÁÚ·ÊÈ΋˜ ηٷÛÙÔÏ‹˜

Ù˘ ¤ÎÊÚ·Û˘ ÙÔ˘ Û˘ÓfiÏÔ˘ ۯ‰fiÓ ÙˆÓ ÁÔÓȉ›ˆÓ ÙÔ˘ à ¯ÚˆÌfiۈ̷ÙÔ˜ ÙˆÓ ıËÏ·ÛÙÈÎÒÓ, ¤ÙÛÈ ÒÛÙ Û οı ‰ÈÏÔÂȉÈÎfi ·ÙÙ·ÚÔ Ó· ¶·È‰È·ÙÚÈ΋ 2008;71:271-276

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°. §·‚Ú¿ÓÔ˜, ƒ. ∞ÁÁÂÏÔÔ‡ÏÔ˘

·Ú·Ì¤ÓÂÈ ÂÓÂÚÁfi ÌfiÓÔ ¤Ó· à ¯ÚˆÌfiۈ̷ Û οı ‰Â‰Ô̤ÓË ¯ÚÔÓÈ΋ ÛÙÈÁÌ‹ (1-2). ∞˘Ùfi Ú·ÎÙÈο ÛËÌ·›ÓÂÈ fiÙÈ ÛÂ Ê˘ÛÈÔÏÔÁÈÎfi ·ÚÛÂÓÈÎfi ¿ÙÔÌÔ (46,ÃÀ) ‰ÂÓ ·Ó·Ì¤ÓÂÙ·È Ó· ·Ú·ÙËÚËı› ÙÔ Ê·ÈÓfiÌÂÓÔ, ÂÓÒ ÛÙËÓ Ù˘È΋ Á˘Ó·›Î· (46,ÃÃ) ı· ˘¿Ú¯ÂÈ ¤Ó· ÂÓÂÚÁfi Î·È ¤Ó· ·‰Ú·Ó¤˜ à ¯ÚˆÌfiۈ̷ ·Ó¿ ‰ÈÏÔÂȉÈÎfi ·ÙÙ·ÚÔ. √ ηÓfiÓ·˜ ·˘Ùfi˜, Ô ÔÔ›Ô˜ Ú·ÎÙÈο ‰È¤ÂÈ ÙÔÓ ·ÚÈıÌfi ÙˆÓ Ã Ô˘ ·ÂÓÂÚÁÔÔÈÔ‡ÓÙ·È, ÔÓÔÌ¿˙ÂÙ·È ÛÙË ‚È‚ÏÈÔÁÚ·Ê›· ηÓfiÓ·˜ Ã-1 Î·È ·ÔÙÂÏ› ÌÈ· ·Ú¿ÌÂÙÚÔ Ù˘ ÏÂÁfiÌÂÓ˘ ˘fiıÂÛ˘ Lyon. ∏ ÙÂÏÂ˘Ù·›· Ï·Ì‚¿ÓÂÈ ÙÔ fiÓÔÌ¿ Ù˘ ·fi ÙËÓ ÚˆÙÂÚÁ¿ÙË Ù˘ ¤Ú¢ӷ˜ ÁÈ· ÙËÓ ·‰Ú·ÓÔÔ›ËÛË ÙÔ˘ Ã, Mary F. Lyon, Ô˘ ‰ËÌÔÛ›Â˘Û ٷ ‚·ÛÈο ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘ Ê·ÈÓÔ̤ÓÔ˘, ‚·ÛÈṲ̂ÓË ÛÂ Â˘Ú‹Ì·Ù· ·fi ÙËÓ ¤Ú¢ӷ ÛÙ· ÔÓÙ›ÎÈ· (3). ŒÙÛÈ, Û‡Ìʈӷ Ì ÙË Lyon, Ë ·‰Ú·ÓÔÔ›ËÛË ÂÁηı›ÛÙ·Ù·È ÓˆÚ›˜ ÛÙËÓ ÂÌ‚Ú˘˚΋ ˙ˆ‹ (ÛÙ¿‰ÈÔ ÂÌʇÙ¢Û˘ ‚Ï·ÛÙÔ·ÛÙ˘), Á›ÓÂÙ·È Ù˘¯·›·, ·ÊÔÚ¿ fiÏÔ ÙÔ ¯ÚˆÌfiۈ̷ Ã Î·È ‰È·ÙËÚÂ›Ù·È ÛÙ·ıÂÚ‹ Û fiÏ· Ù· ·Ú¿ÁˆÁ· ·ÙÙ·Ú· ÙˆÓ ÂfiÌÂÓˆÓ ÁÂÓÂÒÓ. ™Â ·Ó·ÁÓÒÚÈÛË Ù˘ Û˘ÓÔÏÈ΋˜ ÚÔÛÊÔÚ¿˜ Ù˘ Lyon ÛÙËÓ ÂÍȯӛ·ÛË ÙÔ˘ Ú˘ıÌÈÛÙÈÎÔ‡ Ù˘ Ì˯·ÓÈÛÌÔ‡, ÔÏfiÎÏËÚÔ ÙÔ Ê·ÈÓfiÌÂÓÔ Ù˘ ·‰Ú·ÓÔÔ›ËÛ˘ ÂÚÈÁÚ¿ÊÂÙ·È ÛÙË ‚È‚ÏÈÔÁÚ·Ê›· Î·È ˆ˜ Ï˘ÔÓÔÔ›ËÛË (lyonization). ™‹ÌÂÚ·, ÁÓˆÚ›˙Ô˘Ì fiÙÈ ÔÚÈṲ̂Ó˜ ·fi ÙȘ ·Ú·Ì¤ÙÚÔ˘˜ Ô˘ ÚfiÙÂÈÓÂ Ë Lyon ¤¯Ô˘Ó ‰È·ÊÔÚÔÔÈËı›, ·ÏÏ¿ Ô ÎÔÚÌfi˜ Ù˘ ıˆڛ·˜ ·Ú·Ì¤ÓÂÈ ·Î¤Ú·ÈÔ˜. ∂ȉÈÎfiÙÂÚ·, Ô ¯ÚfiÓÔ˜ ÂͤÏÈ͢ ·ÊÔÚ¿ Ú¿ÁÌ·ÙÈ ÙËÓ ·˘Ï¿ÎˆÛË Î·È ·˘Ùfi ÂȂ‚·ÈÒıËΠ·fi ·Ú·ÙËÚ‹ÛÂȘ Û ‰È¿ÊÔÚ· ›‰Ë, fiˆ˜ ÙÔ ÔÓÙ›ÎÈ Î·È ÙÔ Î·ÁÎÔ˘Úfi. ∆· ÂËÚ·˙fiÌÂÓ· ÁÔÓ›‰È· Â›Ó·È ·ÚÎÂÙ¿, ˘¿Ú¯Ô˘Ó fï˜ Î·È ÔÚÈṲ̂ӷ Ô˘ ‰È·Ê‡ÁÔ˘Ó ÙËÓ ·‰Ú·ÓÔÔ›ËÛË, ÙfiÛÔ ÛÙÔÓ ¿ÓıÚˆÔ, fiÛÔ Î·È ÛÙÔ ÔÓÙ›ÎÈ. ∆· ÁÔÓ›‰È· ·˘Ù¿ Ê·›ÓÂÙ·È fiÙÈ Îˆ‰ÈÎÔÔÈÔ‡Ó ÏËÚÔÊÔڛ˜ ÂȉÈΤ˜ ÁÈ· ÙÔ Ê‡ÏÔ, ÒÛÙ ӷ ‰ÈηÈÔÏÔÁÂ›Ù·È Ë ·ÓÈÛfiÙÈÌË ¤ÎÊÚ·Û‹ ÙÔ˘˜ (¿ÚÛË ÁÔÓȉȷ΋˜ ·ÓÙÈÛÙ¿ıÌÈÛ˘). ∂ÈϤÔÓ, Ù· ÁÔÓ›‰È· ·˘Ù¿ ‰ÂÓ ‚Ú›ÛÎÔÓÙ·È Ù˘¯·›· ηٷÓÂÌË̤ӷ ÛÙÔ Ã, ·ÏÏ¿ ·ÓÙ›ıÂÙ· ÂÓÙÔ›˙ÔÓÙ·È ˘Ô¯ÚˆÙÈο Û ÌÂÁ¿ÏË ·fiÛÙ·ÛË ·fi ÙȘ Û˘ÓÙËÚË̤Ó˜ ·ÏÏËÏÔ˘¯›Â˜ line1, ÔÈ Ôԛ˜ Â›Ó·È ··Ú·›ÙËÙ˜ ÁÈ· ÙËÓ Â¤ÎÙ·ÛË Ù˘ ·‰Ú·ÓÔÔ›ËÛ˘ Î·È ÙË ÌÂÙ¤ÂÈÙ· ‰È·Ù‹ÚËÛË Ù˘ ÁÔÓȉȷ΋˜ ηٷÛÙÔÏ‹˜, Ì ÙË ÌÂÙ·ÙÚÔ‹ ÙˆÓ Á‡Úˆ ÙÔ˘˜ ÂÚÈÔ¯ÒÓ Û ÂÙÂÚԯڈ̷ٛÓË. ™Â Û¯¤ÛË Ì ÙË ‰È·Ù‹ÚËÛË ÙÔ˘ ÚÔÙ‡Ô˘ ·‰Ú·ÓÔÔ›ËÛ˘ ÛÙȘ ÂfiÌÂÓ˜ ÁÂÓȤ˜ ΢ÙÙ¿ÚˆÓ, ·Ú·ÙËÚÂ›Ù·È Û¯ÂÙÈ΋ Û˘Ìʈӛ· ÛÙËÓ ÂÈÛÙËÌÔÓÈ΋ ÎÔÈÓfiÙËÙ·, Ì ÂÍ·›ÚÂÛË ÔÚÈṲ̂ӷ ÂÈÚ·Ì·ÙÈο ÌÔÓ٤Ϸ ¿ÚÛ˘ Ù˘ ·‰Ú·ÓÔÔ›ËÛ˘ ̤ۈ ÂÈÁÂÓÂÙÈ΋˜ ·ÔÚÚ‡ıÌÈÛ˘ ‹ ÛÙÔ Ï·›ÛÈÔ Á‹Ú·ÓÛ˘ (1). ∆Ô ˙‹ÙËÌ· ÙÔ˘ Ù˘¯·›Ô˘ ÙÚfiÔ˘ ÂÈÏÔÁ‹˜ ÙÔ˘ ·‰Ú·ÓÔ‡˜ Ã Â›Ó·È ÙÔ ÎÔÚ˘Ê·›Ô ›Ûˆ˜ ÂÚÒÙËÌ· Ô˘ ηÏÂ›Ù·È Ó· ··ÓÙ‹ÛÂÈ Ë Û‡Á¯ÚÔÓË ¤Ú¢ӷ Á‡Úˆ Paediatriki 2008;71:271-276

·fi ÙËÓ ·‰Ú·ÓÔÔ›ËÛË ÙÔ˘ Ã. ∏ ÛËÌÂÚÈÓ‹ ÁÓÒÛË ·Ó·Ê¤ÚÂÈ fiÙÈ ÛÙ· Ì·ÚÛÈÔÊfiÚ· ıËÏ·ÛÙÈο Ë ·‰Ú·ÓÔÔ›ËÛË ˘fiÎÂÈÙ·È Û ηÓfiÓ˜ ÁÔÓȉȷ΋˜ ·ÔÙ‡ˆÛ˘ (·‰Ú·ÓÔÔ›ËÛË ÙÔ˘ ·ÙÚÈ΋˜ ÚÔ¤Ï¢Û˘ Ã). ™Ù· ÙÚˆÎÙÈο ·˘Ùfi ÈÛ¯‡ÂÈ ÌfiÓÔ ÁÈ· ÙÔ˘˜ Â͈ÂÌ‚Ú˘˚ÎÔ‡˜ ÈÛÙÔ‡˜, ÂÓÒ Ë ¤Ûˆ ΢ÙÙ·ÚÈ΋ Ì¿˙· ·ÎÔÏÔ˘ı› Ù˘¯·›Ô ÚfiÙ˘Ô. ∆¤ÏÔ˜, ÛÙÔÓ ¿ÓıÚˆÔ Ë ·‰Ú·ÓÔÔ›ËÛË Â›Ó·È Ù˘¯·›·, ÁÂÁÔÓfi˜ Ô˘ Ô‰ËÁ›, ÛÙ· ı‹Ï·, ÛÙËÓ ¤ÎÊÚ·ÛË ·ÌÊfiÙÂÚˆÓ ÙˆÓ ·ÏÏËÏÔÌfiÚÊˆÓ Û ÂÚ›ÙˆÛË ÌË ÔÌfiÏÔÁˆÓ ÁÔÓȉ›ˆÓ Û οÔÈÔ ÙfiÔ ÙÔ˘ à Û ¿ÏÏË ·Ó·ÏÔÁ›· ¿ÏÏÔÙ (ÏÂÈÙÔ˘ÚÁÈÎfi˜ ̈۷˚ÎÈÛÌfi˜) (2). ∆Ô Ê·ÈÓfiÌÂÓÔ ·˘Ùfi ÁÂÓÈο Ê·›ÓÂÙ·È fiÙÈ ‰Ú· ÚÔÛٷ٢ÙÈο, ÌÂÈÒÓÔÓÙ·˜ ÙËÓ Â›ÙˆÛË ÙˆÓ Ê˘ÏÔÛ‡Ó‰ÂÙˆÓ ÓÔÛËÌ¿ÙˆÓ ÛÙȘ Á˘Ó·›Î˜, Ù· Ú¿ÁÌ·Ù· fï˜ ‰ÂÓ Â›Ó·È ¿ÓÙ· ÙfiÛÔ Û·Ê‹, fiˆ˜ ı· ·Ó·‰Âȯı› ÛÙË Û˘Ó¤¯ÂÈ· Ù˘ ·ÚÔ‡Û·˜ ·Ó·ÛÎfiËÛ˘.

√ Ì˯·ÓÈÛÌfi˜ Ù˘ ÂÈÏÔÁ‹˜ ÙÔ˘ ·‰Ú·ÓÔ‡˜ à ÃÚˆÌÔÛÒÌ·ÙÔ˜ ∏ ·‰Ú·ÓÔÔ›ËÛË ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ à ¤¯ÂÈ ÌÂÏÂÙËı› ÂÎÙÂÓ¤ÛÙÂÚ· ÛÙ· ÔÓÙ›ÎÈ·, ÂÓÒ ÔÈ ÏËÚÔÊÔڛ˜ Ô˘ ‰È·Ù›ıÂÓÙ·È ÁÈ· ¿ÏÏ· ›‰Ë, ÂÔ̤ӈ˜ Î·È ÁÈ· ÙÔÓ ¿ÓıÚˆÔ, Â›Ó·È ÈÔ ·ÔÛ·ÛÌ·ÙÈΤ˜. ™Â οı ÂÚ›ÙˆÛË, Â›Ó·È ϤÔÓ ·Ô‰ÂÎÙfi ·fi fiÏÔ˘˜ fiÙÈ Ë ·‰Ú·ÓÔÔ›ËÛË ‰ÈÂÍ¿ÁÂÙ·È Û 3 ‰È·ÎÚÈÙ¿ ‰È·‰Ô¯Èο ÛÙ¿‰È· Î·È fiÙÈ Ë ÂÈÙ˘¯‹˜ ÂÚ¿ÙˆÛË ÙÔ˘ ηıÂÓfi˜ ·fi ·˘Ù¿ ·ÔÙÂÏ› ·Ó·Áη›·, ·ÏÏ¿ fi¯È ÈηӋ Û˘Óı‹ÎË ÁÈ· ÙËÓ ÔÌ·Ï‹ ÂͤÏÈÍË Î·È ÙˆÓ ÂÔÌ¤ÓˆÓ (4). ™ÙÔ ÚÒÙÔ ÛÙ¿‰ÈÔ Á›ÓÂÙ·È Ë ÂÈÏÔÁ‹ ÙÔ˘ à Ô˘ ı· ·‰Ú·ÓÔÔÈËı›. ∞Ó Î·È ‰ÂÓ ÁÓˆÚ›˙Ô˘Ì ÏÂÙÔ̤ÚÂȘ ÁÈ· ÙÔ Ì˯·ÓÈÛÌfi, Ê·›ÓÂÙ·È fiÙÈ ÂÌϤÎÂÙ·È Û ·˘ÙfiÓ Ë Î·Ù·Ì¤ÙÚËÛË ÙÔ˘ ·ÚÈıÌÔ‡ ÙˆÓ ·˘ÙÔÛˆÌÈÎÒÓ Î·È ÙˆÓ Ã ¯ÚˆÌÔۈ̿وÓ, ÂÓÒ ÙÂÏÈÎfi ·ÔÙ¤ÏÂÛÌ· Â›Ó·È Ë Û˘ÁÎÚfiÙËÛË ÂÓfi˜ Û˘ÌϤÁÌ·ÙÔ˜ ¤Ó·Ú͢ ÛÙÔ Ã Ô˘ ÙÂÏÈο ı· ·‰Ú·ÓÔÔÈËı› Î·È Ë ¤Ó·ÚÍË Ù˘ ÌÂÙ·ÁÚ·Ê‹˜ ÙÔ˘ ÌË ÌÂÙ·ÊÚ·˙fiÌÂÓÔ˘ ÁÔÓȉ›Ô˘ Xist (X inactive specific transcript - ÂȉÈÎfi ÌÂÙ¿ÁÚ·ÊÔ ÙÔ˘ ·‰Ú·ÓÔ‡˜ Ã) (5-6). ªÂ ÙËÓ ¤ÎÊÚ·ÛË ÙÔ˘ ÁÔÓȉ›Ô˘ ÂÎÎÈÓ› ÙÔ ‰Â‡ÙÂÚÔ ÛÙ¿‰ÈÔ ‹ ÛÙ¿‰ÈÔ Ù˘ ÂÍ¿ψÛ˘, ηٿ ÙÔ ÔÔ›Ô ÙÔ Xist RNA ‚·ıÌÈ·›· ηχÙÂÈ fiÏÔ ÙÔ Ã ÌÂÙ·ÎÈÓÔ‡ÌÂÓÔ Î·Ù¿ Ì‹ÎÔ˜ ÙˆÓ ·ÏÏËÏÔ˘¯ÈÒÓ line1 Î·È ÂÌÔ‰›˙ÔÓÙ·˜ ·Ú¿ÏÏËÏ· ÙËÓ ¤ÎÊÚ·ÛË ÙˆÓ ·Ú·Î›ÌÂÓˆÓ ÁÔÓȉ›ˆÓ. °È· ÙËÓ ÔÌ·Ï‹ ÂͤÏÈÍË Ù˘ Ê¿Û˘ ·˘Ù‹˜ ··Ú·›ÙËÙË Â›Ó·È ÌÈ· ¢ڇÙÂÚË ÂÚÈÔ¯‹ ÙÔ˘ à Á‡Úˆ ·fi ÙÔ ÁÔÓ›‰ÈÔ Xist, Ô˘ ¯·Ú·ÎÙËÚ›˙ÂÙ·È Î·È ˆ˜ ΤÓÙÚÔ ·‰Ú·ÓÔÔ›ËÛ˘ (XIC - X inactivation centre) (7-8). ¶Ú¿ÁÌ·ÙÈ, ¤¯ÂÈ ·Ú·ÙËÚËı› fiÙÈ Û ÂÚ›ÙˆÛË ÌÂÙ¿ıÂÛ˘ Û ·˘ÙÔÛˆÌÈÎfi ¯ÚˆÌfiۈ̷, ·‰Ú·ÓÔÔÈÂ›Ù·È ÙÔ ·Ú¿ÁˆÁÔ ¯ÚˆÌfiۈ̷, ÂÓÒ Û ÂÚ›ÙˆÛË ‰ÔÌÈ΋˜ ·ÏÏÔ›ˆÛ‹˜ ÙÔ˘, ÙÔ ˘ÔÏÂÈfiÌÂÓÔ Ã ‰ÂÓ ÌÔÚ› ϤÔÓ Ó· ·‰Ú·ÓÔÔÈËı› (6). ∆¤ÏÔ˜, ÛÙË

Pediatri Jul-Aug 08

30-07-08

15:52

™ÂÏ›‰·273

273

∞‰Ú·ÓÔÔ›ËÛË ÙÔ˘ à ÛÙËÓ ÎÏÈÓÈ΋

Ê¿ÛË Ù˘ ‰È·Ù‹ÚËÛ˘, ÂÈÁÂÓÂÙÈΤ˜ ÙÚÔÔÔÈ‹ÛÂȘ (˘ÂÚÌÂı˘Ï›ˆÛË ÈÛÙÔÓÒÓ Î·È ÓËÛ›‰ˆÓ CpG, ˘Ô·ÎÂÙ˘Ï›ˆÛË ÈÛÙÔÓÒÓ, Û˘ÛÛÒÚ¢ÛË Ì·ÎÚÔÈÛÙÔÓÒÓ) ÛÙ·ıÂÚÔÔÈÔ‡Ó ÙË ÌÂÙ·ÁÚ·ÊÈ΋ ηٷÛÙÔÏ‹ (9-11).

¶ÂÚÈÙÒÛÂȘ ‰È·Ù·Ú·¯‹˜ ÛÙÔ Ì˯·ÓÈÛÌfi Ù˘ Ù˘¯·›·˜ ·‰Ú·ÓÔÔ›ËÛ˘ Ÿˆ˜ ÚԷӷʤÚıËÎÂ, Ë ·‰Ú·ÓÔÔ›ËÛË ÙÔ˘ à ÛÙÔÓ ¿ÓıÚˆÔ Ê˘ÛÈÔÏÔÁÈο Â›Ó·È ÌÈ· ÂÓÙÂÏÒ˜ Ù˘¯·›· ‰ÈÂÚÁ·Û›·. øÛÙfiÛÔ, Û ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ ·Ú·ÙËÚÔ‡ÓÙ·È ·ÔÎÏ›ÛÂȘ ·fi ÙÔÓ Î·ÓfiÓ· ·˘Ùfi, ÔfiÙ Á›ÓÂÙ·È ÏfiÁÔ˜ ÁÈ· ÌË Ù˘¯·›· ·‰Ú·ÓÔÔ›ËÛË, ÌÈ· ηٿÛÙ·ÛË ÂÍ·ÈÚÂÙÈο ÛËÌ·ÓÙÈ΋, ÏfiÁˆ ÙˆÓ Èı·ÓÒÓ ÚÔÂÎÙ¿ÛÂÒÓ Ù˘ ÁÈ· ÙËÓ ÎÏÈÓÈ΋ Ú¿ÍË. ∏ ÂÚÌËÓ›· ÙÔ˘ Ê·ÈÓÔ̤ÓÔ˘ ·˘ÙÔ‡ ÌÔÚ› Ó· Â›Ó·È Î·Ù¿ ‚¿ÛË ‰ÈÏ‹: ›Ù ÂÍ·Ú¯‹˜ Ë ÂÈÏÔÁ‹ Á›ÓÂÙ·È Ì ÚÔÙ›ÌËÛË ÁÈ· οÔÈÔ ·fi Ù· ‰‡Ô à ¯ÚˆÌÔÛÒÌ·Ù· (ÚˆÙÔÁÂÓ‹˜ ÂÈÏÔÁ‹) ›ÙÂ, ÂÓ·ÏÏ·ÎÙÈο, Ë ÂÈÏÔÁ‹ Á›ÓÂÙ·È Ù˘¯·›·, ·ÏÏ¿ οÔÈÔ˜ ·fi ÙÔ˘˜ ‰˘Ô ÏËı˘ÛÌÔ‡˜ ΢ÙÙ¿ÚˆÓ Ô˘ ÚÔ·ÙÔ˘Ó (Ì ÂÓÂÚÁfi ÌËÙÚÈÎfi Ã Î·È Ì ÂÓÂÚÁfi ·ÙÚÈÎfi Ã, ·ÓÙ›ÛÙÔȯ·) ·ÔÎÙ¿ Ô˘ÛÈ·ÛÙÈÎfi ÏÂÔÓ¤ÎÙËÌ· ÂÈ‚›ˆÛ˘ (‹, ·ÓÙ›ÛÙÔȯ·, ·‰˘Ó·Ì›· ÂÈ‚›ˆÛ˘), Ì ·ÔÙ¤ÏÂÛÌ· Ôχ Û‡ÓÙÔÌ· Ë ÌÈ· ·Ú·ÏÏ·Á‹ Ó· ÂÎÚÔÛˆÂ›Ù·È ϤÔÓ ÏÂÈÔ„ËÊÈο ‹ Î·È ·ÔÎÏÂÈÛÙÈο ·ÎfiÌË ÛÙÔÓ ÏËı˘ÛÌfi (‰Â˘ÙÂÚÔÁÂÓ‹˜ ÂÈÏÔÁ‹ - ÂÎÏÂÎÙÈÎfi˜ ΢ÙÙ·ÚÈÎfi˜ ÔÏÏ·Ï·ÛÈ·ÛÌfi˜ ‹/Î·È ı¿Ó·ÙÔ˜). ™ÙȘ ÂÚÈÙÒÛÂȘ ÂΛӘ, fiÔ˘ Ë ÌË Ù˘¯·›· ·‰Ú·ÓÔÔ›ËÛË ÌÔÚ› Ó· ÂÚÌËÓ¢Ù›, ·Ó‹ÎÔ˘Ó Î˘Ú›ˆ˜ ÔÈ ‰ÔÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÙÔ˘ Ã. ™ÙȘ ÂÚÈÙÒÛÂȘ ·˘Ù¤˜, ›Ù ÙÔ ¤Ó· ÌfiÓÔ Ã ‰È·ı¤ÙÂÈ ·Î¤Ú·ÈÔ Î¤ÓÙÚÔ ·‰Ú·ÓÔÔ›ËÛ˘, ÔfiÙÂ Î·È Î·Ù·ÛÙ¤ÏÏÂÙ·È (.¯. Û ÂÚ›ÙˆÛË ‰·ÎÙ˘ÏÈÔÂȉԇ˜ Ã, fiÔ˘ ÙÔ Ê˘ÛÈÔÏÔÁÈÎfi Ã Â›Ó·È ·ÓÂÓÂÚÁfi) ›ÙÂ, ·ÓÙ›ıÂÙ·, ÙÔ Î¤ÓÙÚÔ ·‰Ú·ÓÔÔ›ËÛ˘ ¤¯ÂÈ ÌÂÙ·ÊÂÚı› ÛÙÔ Ï·›ÛÈÔ ÌÂÙ¿ıÂÛ˘, ÔfiÙ ÂÎÊÚ¿˙ÔÓÙ·È ÌfiÓÔ Ù· Ê˘ÛÈÔÏÔÁÈο ÔÌfiÏÔÁ· ¯ÚˆÌÔÛÒÌ·Ù· Î·È ÙÔ ¿ÙÔÌÔ ·Ú·Ì¤ÓÂÈ ·Û˘Ìو̷ÙÈÎfi (12-14). ∆¤ÙÔȘ ¯ÚˆÌÔÛˆÌÈΤ˜ ·ÓˆÌ·Ï›Â˜ ¤¯Ô˘Ó ·Ó·ÊÂÚı› ˆ˜ (Û˘Ó)˘‡ı˘Ó˜ ÁÈ· ‰È¿ÊÔÚ· ÎÏËÚÔÓÔÌÈο Ó¢ÚÔÁÂÓÂÙÈο Û‡Ó‰ÚÔÌ·, ·ÓÂÍ¿ÚÙËÙ· ·Ó ÙÔ ˘‡ı˘ÓÔ ÁÔÓ›‰ÈÔ ÁÈ’ ·˘Ù¿ ¤¯ÂÈ ÂÓÙÔÈÛÙ› ÛÙÔ Ã ¯ÚˆÌfiۈ̷, fiˆ˜ ÙÔ Barth (15), ÙÔ West (16), ÙÔ Pelizaeus-Merzbacher (17), ÙÔ Lesch-Nyhan (18), ÙÔ Rett (19-20), ÙÔ Kabuki (21-22), ·ÏÏ¿ Î·È ÙÔ RussellSilver (23). ∆Ô Ê·ÈÓfiÌÂÓÔ skewing Î·È Ë ÎÏÈÓÈ΋ ÙÔ˘ ·ÔÙ›ÌËÛË ™ÙËÓ ÚÔËÁÔ‡ÌÂÓË ·Ú¿ÁÚ·ÊÔ ·Ó·Ê¤ÚıËÎ·Ó ÂÚÈÙÒÛÂȘ ÌË Ù˘¯·›·˜ ·‰Ú·ÓÔÔ›ËÛ˘, ÛÙȘ Ôԛ˜ ÂÚÌËÓ›· ÌÔÚ› Ó· ‰Ôı› Ì ‚¿ÛË ÙË ‰È·Ù·Ú·¯‹ ÛÙÔ Ì˯·ÓÈÛÌfi ÂÍ¿ψÛ˘ ÙÔ˘ Ê·ÈÓÔ̤ÓÔ˘ ηÈ, ΢ڛˆ˜, ÂÛÙÈ¿˙ÔÓÙ·˜ ÛÙËÓ ·ÒÏÂÈ· ·ÎÂÚ·ÈfiÙËÙ·˜ ÙÔ˘

ΤÓÙÚÔ˘ ·‰Ú·ÓÔÔ›ËÛ˘. Ÿˆ˜ η٤ÛÙË Û·Ê¤˜, Ë ÏÂÙÔÌÂÚ‹˜ ÌÂϤÙË ÙÔ˘ ηڢÔÙ‡Ô˘ ÙˆÓ ·ÙfiÌˆÓ ·˘ÙÒÓ, ÛÂ Û˘Ó‰˘·ÛÌfi Ì ·Ó·˙‹ÙËÛË Ù˘ ÂÚÈÔ¯‹˜ ÙÔ˘ ΤÓÙÚÔ˘ ·‰Ú·ÓÔÔ›ËÛ˘ ÁÈ· ¤ÏÂÁ¯Ô Ù˘ ·ÎÂÚ·ÈfiÙËÙ¿˜ Ù˘ (΢ڛˆ˜ Ì ÙË Ì¤ıÔ‰Ô ÙÔ˘ ÊıÔÚ›˙ÔÓÙ· in situ ˘‚ÚȉÈÛÌÔ‡ (fluorescence in situ hybridization FISH) ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û ·ÍÈfiÈÛÙË Û˘Ì‚Ô˘Ï¢ÙÈ΋ ηıÔ‰‹ÁËÛË, ηıÒ˜ Ë ÔÔÈ·‰‹ÔÙ ‰ÔÌÈ΋ ·ÏÏÔ›ˆÛË ÛÙËÓ ÂÚÈÔ¯‹ ÙÔ˘ ÁÔÓȉ›Ô˘ Xist (Û˘Ì‚ÔÏÈ˙fiÌÂÓÔ˘ XIST ÛÙËÓ ÂÚ›ÙˆÛË ÙÔ˘ ·ÓıÚÒÔ˘) Î·È ÛÙȘ Ú˘ıÌÈÛÙÈΤ˜ ÙÔ˘ ·ÏÏËÏÔ˘¯›Â˜ ηıÈÛÙ¿ ÙÔ ¯ÚˆÌfiۈ̷-ÊÔÚ¤· Ù˘ ‚Ï¿‚˘ ·Î·Ù¿ÏÏËÏÔ ÁÈ· ·‰Ú·ÓÔÔ›ËÛË. ∆Ô Î·Ù¿ fiÛÔ ·˘Ù‹ Ë ÌË Ù˘¯·›· ÂÈÏÔÁ‹ Â›Ó·È Â˘ÓÔ˚΋ ‹ ÌË ÁÈ· ÙÔ ¿ÙÔÌÔ ÂÍ·ÚÙ¿Ù·È ·fi ÙÔ ·Ó Ë ÏËÚÔÊÔÚ›· Ô˘ ‰ÂÓ ÂÎÊÚ¿˙ÂÙ·È ÛÙÂÚ› ·fi ÙÔ ¿ÙÔÌÔ ··Ú·›ÙËÙ· ÏÂÈÙÔ˘ÚÁÈο ÁÔÓȉȷο ÚÔ˚fiÓÙ· ‹, ·ÓÙ›ıÂÙ·, ÂÚȤ¯ÂÈ ·ÏÏÔȈ̤ÓË ÁÂÓÂÙÈ΋ ÏËÚÔÊÔÚ›· Ô˘ ÂÌÔ‰›˙ÂÙ·È Ì ÙÔÓ ÙÚfiÔ ·˘Ùfi Ó· ÂÎÊÚ·ÛÙ› Û ‚¿ÚÔ˜ ÙÔ˘ ·ÙfiÌÔ˘ (1-2,24). ™Â ÔÚÈṲ̂Ó˜ ÂÚÈÙÒÛÂȘ, ÂÓÒ ‰ÂÓ ÂÓÙÔ›˙ÂÙ·È ¯ÚˆÌÔÛˆÌÈ΋ ·ÓˆÌ·Ï›· Î·È ÙÔ Î¤ÓÙÚÔ ·‰Ú·ÓÔÔ›ËÛ˘ Â›Ó·È ·Î¤Ú·ÈÔ, ÙÔ ¿ÙÔÌÔ ÂÌÊ·Ó›˙ÂÈ ÂÎÏÂÎÙÈ΋ ·‰Ú·ÓÔÔ›ËÛË ÙÔ˘ ÂÓfi˜ à ¯ÚˆÌÔÛÒÌ·ÙÔ˜ (∂ÈÎfiÓ· 1). ∞˘Ùfi ÌÔÚ› Ó· ·ÊÔÚ¿ ÌÈ· ‹È· ·fiÎÏÈÛË ·fi ÙÔ ·Ó·ÌÂÓfiÌÂÓÔ 50%-50%, ÒÛÙ ӷ ÌÔÚ› Ó· ıˆÚËı› Ê˘ÛÈÔÏÔÁÈ΋ ·Ú·ÏÏ·Á‹ ÙÔ˘ ̈۷˚ÎÈÛÌÔ‡, Ó· ÂÈÙ›ÓÂÙ·È ‚·ıÌÈ·›· ·fi ÁÂÓÈ¿ Û ÁÂÓÈ¿, Ì ·Ó¿ÏÔÁË ÂÈ‚¿Ú˘ÓÛË ÛÙÔ Ê·ÈÓfiÙ˘Ô [ÁÔÓȉȷ΋ Â›Û¢ÛË, fiˆ˜ .¯. Û˘Ì‚·›ÓÂÈ ÛÙËÓ ·ÓȉڈÙÈ΋ ‰˘ÛÏ·Û›· ÙÔ˘ Â͈‰¤ÚÌ·ÙÔ˜ - X linked hypohidrotic ectodermal dysplasia (XHID)] ‹ Ó· ·ÊÔÚ¿ ηıÔÏÈ΋ ÂÈÏÔÁ‹ ÂÓfi˜ à ˆ˜ ·‰Ú·ÓÔ‡˜ (skewing). ªÈ· Èı·Ó‹ ÂÚÌËÓ›· ÙÔ˘ Ê·ÈÓÔ̤ÓÔ˘ Ù˘ ·Û‡ÌÌÂÙÚ˘ ÂÈÏÔÁ‹˜ ÙÔ˘ ·‰Ú·ÓÔ‡˜ à (skewing) ·ÊÔÚ¿ ‰È·Ù·Ú·¯¤˜ ÛÙÔ Â›Â‰Ô Ù˘ ÂÈÁÂÓÂÙÈ΋˜. °È· ·Ú¿‰ÂÈÁÌ·, ¤¯ÂÈ ·Ú·ÙËÚËı› fiÙÈ ÌË Ù˘¯·›· ·‰Ú·ÓÔÔ›ËÛË Û˘Óԉ‡ÂÈ Û‡Ó‰ÚÔÌ· Ì Ì˯·ÓÈÛÌfi ÁÔÓȉȷ΋˜ ·ÔÙ‡ˆÛ˘, fiˆ˜ ÙÔ Wiedermann-Beckwith (25). ¢Â‰Ô̤ÓÔ˘ fiÙÈ Â›Ó·È ·ԉ‰ÂÈÁ̤ÓÔ fiÙÈ Ë ·‰Ú·ÓÔÔ›ËÛË ˘fiÎÂÈÙ·È Û Ì˯·ÓÈÛÌÔ‡˜ ·ÔÙ‡ˆÛ˘ Û ¿ÏÏ· ›‰Ë ÂÎÙfi˜ ÙÔ˘ ·ÓıÚÒÔ˘ Î·È ÌÂÙ¿ÁÚ·Ê· ·ÓÙÈı¤ÙÔ˘ ÓÔ‹Ì·ÙÔ˜ ÚÔ˜ ÙÔ Xist RNA (Tsix RNA) ÂÌϤÎÔÓÙ·È ÛÙÔ Ì˯·ÓÈÛÌfi ÂÈÏÔÁ‹˜ Î·È ‰È·ı¤ÙÔ˘Ó Ú˘ıÌÈÛÙÈ΋ ÂÚÈÔ¯‹ Ì ÌÂÙ·‚ÏËÙfi ÚfiÙ˘Ô ÌÂı˘Ï›ˆÛ˘, Â›Ó·È Èı·ÓfiÓ ¤Ó·˜ ·Ó¿ÏÔÁÔ˜ Ì˯·ÓÈÛÌfi˜ Ó· ·ÓÙÈÛÙÔȯ› Î·È ÛÙÔÓ ¿ÓıÚˆÔ. øÛÙfiÛÔ, ÂÈÛËÌ·›ÓÂÙ·È fiÙÈ, ÁÈ· ÙËÓ ÒÚ·, ÙÔ ·ÓÙ›ÛÙÔÈ¯Ô ÙÔ˘ Tsix RNA ÚÔ˚fiÓ ÛÙÔÓ ¿ÓıÚˆÔ (TSIX RNA) ‰ÂÓ Ê·›ÓÂÙ·È Ó· ¤¯ÂÈ ÔÔÈ·‰‹ÔÙ ÏÂÈÙÔ˘ÚÁÈÎfiÙËÙ· (1, 7-9). ¶·Ú’ fiÏ’ ·˘Ù¿, Ë ÛËÌ·Û›· Ù˘ ÌÂı˘Ï›ˆÛ˘ ÁÈ· ÙËÓ ÔÌ·Ï‹ ‰È·Ù‹ÚËÛË Ù˘ ·‰Ú·ÓÔÔ›ËÛ˘ ÛÙÔÓ ¿ÓıÚˆÔ ‰ÂÓ ·ÌÊÈÛ‚ËÙ›ٷÈ, ÂÓÒ ˘¿Ú¯Ô˘Ó Î·È ÁÓˆÛÙ¿ ·Ú·‰Â›ÁÌ·Ù· ÓfiÛÔ˘ Û ÂÚ›ÙˆÛË ‰È·Ù·Ú·¯‹˜ ¶·È‰È·ÙÚÈ΋ 2008;71:271-276

Pediatri Jul-Aug 08

30-07-08

15:52

™ÂÏ›‰·274

274

°. §·‚Ú¿ÓÔ˜, ƒ. ∞ÁÁÂÏÔÔ‡ÏÔ˘

∂ÈÎfiÓ· 1. ∞‰Ú·ÓÔÔ›ËÛË ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ Ã Î·È ÚfiÙ˘· ÂÈÏÔÁ‹˜ ÙÔ˘ ·‰Ú·ÓÔ‡˜ Ã. º˘ÛÈÔÏÔÁÈο, Ë ÂÈÏÔÁ‹ ·ÊÔÚ¿ ÙÔ ÌËÙÚÈÎfi ‹ ·ÙÚÈÎfi Ã Ù˘¯·›· (·). ™Â ÂÚÈÙÒÛÂȘ fï˜ ‰ÔÌÈ΋˜ ·ÓˆÌ·Ï›·˜ Ô˘ ÂÚÈÏ·Ì‚¿ÓÂÈ ÙÔ Î¤ÓÙÚÔ ·‰Ú·ÓÔÔ›ËÛ˘, ÙÔ ·Ú¿ÁˆÁÔ ¯ÚˆÌfiۈ̷ ·‰Ú·ÓÔÔÈÂ›Ù·È ˘Ô¯ÚˆÙÈο (‚). ∞ÓÙ›ıÂÙ·, ·Ó Ë ·ÓˆÌ·Ï›· ‰È·Ù·Ú¿ÛÛÂÈ ÙËÓ ·ÎÂÚ·ÈfiÙËÙ· ÙÔ˘ XIC (.¯. ‰·ÎÙ˘ÏÈÔÂȉ¤˜ Ã), ·˘Ùfi ·Ú·Ì¤ÓÂÈ ·Ó·ÁηÛÙÈο ÂÓÂÚÁfi (Á). ∆¤ÏÔ˜, ˘¿Ú¯Ô˘Ó Î·È ÂÚÈÙÒÛÂȘ ·‰ÈηÈÔÏfiÁËÙ˘ ¤ˆ˜ Û‹ÌÂÚ· ÂÎÏÂÎÙÈ΋˜ ·‰Ú·ÓÔÔ›ËÛ˘ ÙÔ˘ ÂÓfi˜ à (ηıÔÏÈ΋˜ ‹ ηٿ Ì›˙ÔÓ· ÏÂÈÔ„ËÊ›· ÙˆÓ ÛˆÌ·ÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ ÙÔ˘ ·ÙfiÌÔ˘-ÊÔÚ¤·) Ì ·ÍÈÔÛËÌ›ˆÙ˜ ÎÏÈÓÈΤ˜ ÚÔÂÎÙ¿ÛÂȘ (skewing, ‰).

Ù˘, fiˆ˜ .¯. ÙÔ Û‡Ó‰ÚÔÌÔ ICF (immunodeficiency, centromeric instability, facial distortion) Û ÂÚ›ÙˆÛË ÌÂÙ¿ÏÏ·Í˘ ÛÙÔ ÁÔÓ›‰ÈÔ Ù˘ ÌÂı˘ÏÔÙÚ·ÓÛÊÂÚ¿Û˘ DNMT3B (26-27). ™ÙÔ ›‰ÈÔ Ï·›ÛÈÔ, ¤¯ÂÈ ÌÂÏÂÙËı› Ë Èı·Ó‹ Û‡Ó‰ÂÛË Ù˘ ·‰Ú·ÓÔÔ›ËÛ˘ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ à Ì ÙËÓ ÚԉȿıÂÛË ÁÈ· ηÚÎÈÓÔÁ¤ÓÂÛË ‹ ÙËÓ Èı·Ó‹ ·ÓÙ·fiÎÚÈÛË ÛÙË ¯ËÌÂÈÔıÂÚ·›·. ∂ȉÈÎfiÙÂÚ·, ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÂÓ˙˘ÌÈÎÔ‡ Ì˯·ÓÈÛÌÔ‡ ÂϤÁ¯Ô˘ Ù˘ ·ÎÂÙ˘Ï›ˆÛ˘ Î·È ÌÂı˘Ï›ˆÛ˘ Â›Ó·È ‰˘Ó·ÙfiÓ Ó· ÂËÚ¿ÛÔ˘Ó ÙfiÛÔ ÙËÓ ·‰Ú·ÓÔÔ›ËÛË, fiÛÔ Î·È ÙËÓ ¤ÎÊÚ·ÛË ÚˆÙÔ-ÔÁÎÔÁÔÓȉ›ˆÓ, fiˆ˜ Ú¿ÁÌ·ÙÈ ¤¯ÂÈ ·Ú·ÙËÚËı› ÛÂ Û˘Ì·Á‹ ÓÂÔÏ¿ÛÌ·Ù· ÙˆÓ ÂÓËÏ›ÎˆÓ (.¯. Ì·ÛÙÔ‡, ÚÔÛÙ¿ÙË) (28-30). ∂ÈϤÔÓ, Ë ·‰Ú·ÓÔÔ›ËÛË ·ÔÙÂÏ› ¤Ó· ¯Ú‹ÛÈÌÔ ÂÚÁ·ÏÂ›Ô ÁÈ· ÙËÓ ·fi‰ÂÈÍË Ù˘ ÌÔÓÔÎψÓÈ΋˜ ÚÔ¤Ï¢Û˘ ÙˆÓ Î·ÚÎÈÓÈÎÒÓ Î˘ÙÙ¿ÚˆÓ, ÌÈ· Î·È ÛÙËÓ ÂÚ›ÙˆÛË ·˘Ù‹ ı· Ú¤ÂÈ fiÏ· Ù· ·Ú¿ÁˆÁ· ·ÙÙ·Ú· Ó· ‰È·ÙËÚÔ‡Ó ÙÔ ›‰ÈÔ Ã ¯ÚˆÌfiۈ̷ ÂÓÂÚÁfi (31-34). ∆¤ÏÔ˜, ı· Ú¤ÂÈ Ó· ÛËÌÂȈı› Ë ÛËÌ·ÓÙÈ΋ ·Ú·Ù‹ÚËÛË fiÙÈ Ë ¤ÎÊÚ·ÛË ÙÔ˘ ÔÁÎÔηٷÛÙ·ÏÙÈÎÔ‡ ÁÔÓȉ›Ô˘ BRCA1 Û˘Ì‚·‰›˙ÂÈ Ì ·˘Ù‹ ÙÔ˘ XIST, ÁÂÁÔÓfi˜ Ô˘ ÛËÌ·›ÓÂÈ ·ÊÂÓfi˜ fiÙÈ ÌÔÚ› Ó· Û˘ÌÌÂÙ¤¯ÂÈ ÛÙÔ ÌËPaediatriki 2008;71:271-276

¯·ÓÈÛÌfi ¤Ó·Ú͢-ÂÍ¿ψÛ˘ Ù˘ ·‰Ú·ÓÔÔ›ËÛ˘, ·ÊÂÙ¤ÚÔ˘ fiÙÈ Ô ÂÓÙÔÈÛÌfi˜ ÙÔ˘˜ ÌÔÚ› Ó· ¤¯ÂÈ ÎÏÈÓÈ΋ ·Í›· ˆ˜ ¢ÓÔ˚Îfi˜ ÚÔÁÓˆÛÙÈÎfi˜/ÚÔ‚ÏÂÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ (35-36). ™Â ÔÚÈṲ̂Ó˜ ·ÎfiÌ· ÂÚÈÙÒÛÂȘ, Ô Ê˘ÛÈÔÏÔÁÈÎfi˜ ̈۷˚ÎÈÛÌfi˜ Ê·›ÓÂÙ·È Ó· ÂÎÙÚ¤ÂÙ·È ‚·ıÌÈ·›· ÚÔ˜ ·Û‡ÌÌÂÙÚË ÂÈÏÔÁ‹, fiˆ˜ Û˘Ì‚·›ÓÂÈ ÛÙËÓ ÚÔ·Ó·ÊÂÚı›۷ ÂÚ›ÙˆÛË Ù˘ XHID (37-38). ∏ ÎÏÈÓÈ΋ ÛËÌ·Û›· ·˘ÙÔ‡ ÙÔ˘ ¯·Ú·ÎÙËÚÈÛÙÈÎÔ‡ ‰ÂÓ Â›Ó·È ¿ÓÙ· Û·Ê‹˜ Î·È Ù· ·ÔÙÂϤÛÌ·Ù· ÛÙË ‚È‚ÏÈÔÁÚ·Ê›· Â›Ó·È Ì¿ÏÏÔÓ Û˘Áί˘Ì¤Ó·, ·Ó Î·È Ê·›ÓÂÙ·È fiÙÈ ˘¿Ú¯ÂÈ ÈÛ¯˘Ú‹ ÔÈÎÔÁÂÓÂȷ΋ ÎÏËÚÔÓfiÌËÛË Ù˘ ȉÈfiÙËÙ·˜, Ì ÔÈΛÏÔ˘ fï˜ ‚·ıÌÔ‡ ‰ÈÂÈÛ‰˘ÙÈÎfiÙËÙ· (38). °È· ·Ú¿‰ÂÈÁÌ·, ¤¯ÂÈ ÂÚÈÁÚ·Ê› Û˘Û¯¤ÙÈÛË Ù˘ ‡·Ú͢ ÈÛ¯˘Ú¿ ·Û‡ÌÌÂÙÚ˘ ·‰Ú·ÓÔÔ›ËÛ˘ (ۯ‰fiÓ 100% ÂÎÏÂÎÙÈ΋ ·ÔÛÈÒËÛË ÙÔ˘ ·ÙÚÈÎÔ‡ ‹ ÌËÙÚÈÎÔ‡ à Û fiÏ· Ù· ۈ̷ÙÈο ·ÙÙ·Ú·) Ì ÙËÓ ÂÌÊ¿ÓÈÛË ·˘ÙÔ·ÓÔÛ›·˜ (39-41), ÎÏËÚÔÓÔÌÈÎÒÓ ÂÓ‰ÔÎÚÈÓÔ·ıÂÈÒÓ (42) ‹ Â·Ó·Ï·Ì‚·ÓfiÌÂÓˆÓ ·˘ÙfiÌ·ÙˆÓ ·Ô‚ÔÏÒÓ (recurrent spontaneous abortions - RSA) (43-46). ∆· Â˘Ú‹Ì·Ù· ·˘Ù¿ ‰ÂÓ ¤¯Ô˘Ó ·ÎfiÌ· Â·ÏËı¢ı› Ì ÔÏ˘ÎÂÓÙÚÈΤ˜ ÌÂϤÙ˜ ÌÂÁ¿Ï˘ Îϛ̷η˜, ÂÓÒ ÂÈϤÔÓ Ê·›ÓÂÙ·È Ó· ˘¿Ú¯ÂÈ Û‡Ó‰ÂÛË ÙÔ˘ ÂÈ¤‰Ô˘ Ù˘

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∞‰Ú·ÓÔÔ›ËÛË ÙÔ˘ à ÛÙËÓ ÎÏÈÓÈ΋

·Û˘ÌÌÂÙÚ›·˜ Ì ÙË Á‹Ú·ÓÛË ÙˆÓ ˆÔıËÎÒÓ Î·È ÙËÓ ÂÌÊ¿ÓÈÛË ÂÈÏÔÎÒÓ, ÙfiÛÔ Î·Ù¿ ÙËÓ ·fiÂÈÚ· Û‡ÏÏ˄˘, fiÛÔ Î·È Î·Ù¿ ÙÔÓ ÙÔÎÂÙfi (.¯. ÂÎÏ·Ì„›·) (4750). ∫·Ù¿ Û˘Ó¤ÂÈ·, Ë ÂÌÂÈÚ›· Ô˘ ¤¯ÂÈ ·ÔÎÙËı› ̤¯ÚÈ Û‹ÌÂÚ· Û ·ÁÎfiÛÌÈÔ Â›Â‰Ô ‰ÈηÈÔÏÔÁ› Ú¿ÁÌ·ÙÈ Î¿ÔÈ· ·ÓËÛ˘¯›· ÁÈ· ÙȘ Èı·Ó¤˜ ÚÔÂÎÙ¿ÛÂȘ ÙÔ˘ Ê·ÈÓÔ̤ÓÔ˘ Ù˘ ·Û‡ÌÌÂÙÚ˘ ·‰Ú·ÓÔÔ›ËÛ˘ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ à (skewing) ÁÈ· ÙË ÌÂÙ¤ÂÈÙ· ÂͤÏÈÍË Ù˘ ˘Á›·˜ Ù˘ ÌËÙ¤Ú·˜ Î·È ÙˆÓ ıËÏ˘ÎÒÓ ·ÔÁfiÓˆÓ, fï˜ ‰ÂÓ ıˆÚÂ›Ù·È fiÙÈ ·ÔÙÂÏ› Û·Ê‹ ¤Ó‰ÂÈÍË ·ıÔÏÔÁ›·˜ Ô˘ Ó· Û˘ÓÂ¿ÁÂÙ·È ¿ÌÂÛË ·Ó¿ÁÎË È·ÙÚÈ΋˜ ·Ú¤Ì‚·Û˘.

™˘ÌÂÚ¿ÛÌ·Ù· ∏ ÌË Ù˘¯·›· ·‰Ú·ÓÔÔ›ËÛË ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ à ÌÔÚ› Ó· ·ÔÙÂÏ› ¤Ó· ‡ÚËÌ· ¯ˆÚ›˜ ÂÚ·ÈÙ¤Úˆ ÎÏÈÓÈ΋ ÛËÌ·Û›· ÁÈ· οÔÈ· ÔÈÎÔÁ¤ÓÂÈ·, ·ÏÏ¿ Û ·ÚÎÂÙ¤˜ ÂÚÈÙÒÛÂȘ ÌÔÚ› Ó· ‰È·ÙËÚ› ÚÔÁÓˆÛÙÈ΋ ‹/Î·È ÚÔ‚ÏÂÙÈ΋ ·Í›·, ÙfiÛÔ ÁÈ· ÙËÓ Èı·ÓfiÙËÙ· ÓfiÛËÛ˘, fiÛÔ Î·È ÁÈ· ÙË ‚·Ú‡ÙËÙ· Ù˘ ÎÏÈÓÈ΋˜ ÂÈÎfiÓ·˜, ·ÏÏ¿ Î·È ÙËÓ Èı·ÓfiÙËÙ· ÌÂÙ¿‰ÔÛ˘ Ù˘ ÓfiÛÔ˘ ÛÙȘ ·ÔÁfiÓÔ˘˜, ÙfiÛÔ ·˘ÙÔ‡ÛÈ·˜, fiÛÔ Î·È Û ‚·ıÌÈ·›· ÂȉÂÈÓÔ‡ÌÂÓË ÌÔÚÊ‹ (Ê·ÈÓfiÌÂÓÔ ÁÔÓȉȷ΋˜ ÂÓ›Û¯˘Û˘ ‹ ÁÔÓȉȷ΋˜ Â›Û¢Û˘). ¶ÚfiÎÂÈÙ·È ¯ˆÚ›˜ ·ÌÊÈ‚ÔÏ›· ÁÈ· ¤Ó· Ê·ÈÓfiÌÂÓÔ ÔÏ˘‰È¿ÛÙ·ÙÔ Î·È ÂÚ›ÏÔÎÔ, ÙÔ ÔÔ›Ô ·ÊÔÚ¿ fi¯È ÌfiÓÔ ÙÔ˘˜ ÎÏÈÓÈÎÔ‡˜ ÁÂÓÂÙÈÛÙ¤˜ Î·È ÌÔÚÈ·ÎÔ‡˜ ‚ÈÔÏfiÁÔ˘˜, ·ÏÏ¿ Î·È ÌÈ· ÛÂÈÚ¿ ·fi ÂȉÈÎfiÙËÙ˜ Ô˘ Ê·›ÓÂÙ·È Ó· ÂËÚ¿˙ÔÓÙ·È ·fi ÙȘ ÎÏÈÓÈΤ˜ Ù˘ ÚÔÂÎÙ¿ÛÂȘ, fiˆ˜ Ë ¶·È‰È·ÙÚÈ΋, Ë ¶·ıÔÏÔÁ›·, Ë ƒÂ˘Ì·ÙÔÏÔÁ›·, Ë ∂Ó‰ÔÎÚÈÓÔÏÔÁ›· Î·È Ë √ÁÎÔÏÔÁ›·. ∞ÛÊ·ÏÒ˜, Ë ¤ÏÏÂÈ„Ë ÔÏÏÒÓ ÛÙÔȯ›ˆÓ ‰ËÌÈÔ˘ÚÁ› ÛËÌ·ÓÙÈΤ˜ ‰˘ÛÎÔϛ˜ ÛÙËÓ ·ÍÈÔÏfiÁËÛË ÙÔ˘ Ê·ÈÓÔ̤ÓÔ˘ Î·È ÛÙËÓ ·ÚÔ¯‹ ¤ÁηÈÚ˘ Î·È ¤Á΢Ú˘ ÏËÚÔÊfiÚËÛ˘ Î·È Û˘Ì‚Ô˘Ï¢ÙÈ΋˜ ηıÔ‰‹ÁËÛ˘, fiˆ˜ ··ÈÙ› Ë Û‡Á¯ÚÔÓË È·ÙÚÈ΋ Ú·ÎÙÈ΋, ÒÛÙÂ Ô È·ÙÚfi˜ Û‹ÌÂÚ· Ó· Â›Ó·È Û ı¤ÛË Ó· ÚԂ› ÌfiÓÔ Û ÁÂÓÈΤ˜ Û˘ÛÙ¿ÛÂȘ. ªÂ ÙË ‚ÂÏÙ›ˆÛË ÙˆÓ ÌÔÚÈ·ÎÒÓ ‰È·ÁÓˆÛÙÈÎÒÓ ÌÂıfi‰ˆÓ fï˜ Î·È ÙËÓ ÂÈÛ·ÁˆÁ‹ Û‡Á¯ÚÔÓˆÓ Û˘ÛÙËÌ¿ÙˆÓ È·ÙÚÈ΋˜ ÏËÚÔÊÔÚÈ΋˜ - ÏÂÈÙÔ˘ÚÁÈ΋˜ ÁÔÓȉȈ̷ÙÈ΋˜ ·Ó·Ì¤ÓÂÙ·È ÔÏϤ˜ ·fi ÙȘ ÛËÌÂÚÈÓ¤˜ ·Ôڛ˜ Ó· ··ÓÙËıÔ‡Ó ÛÙÔ ÂÁÁ‡˜ ̤ÏÏÔÓ, Û fiÊÂÏÔ˜ ÙÔ˘ ¿Û¯ÔÓÙÔ˜ Û˘Ó·ıÚÒÔ˘, ·ÏÏ¿ Î·È Ù˘ ¢ËÌÂÚ›·˜ Ù˘ ÎÔÈÓfiÙËÙ·˜ ÛÙÔ Û‡ÓÔÏfi Ù˘. ∂˘¯·ÚÈÛٛ˜ √ È·ÙÚfi˜ ·ÚÈÔ˜ §·‚Ú¿ÓÔ˜ Ï·Ì‚¿ÓÂÈ ˘ÔÙÚÔÊ›· ‰È‰·ÎÙÔÚÈÎÒÓ ÛÔ˘‰ÒÓ ·fi ÙÔ ÿ‰Ú˘Ì· ¶ÚÔÔÓÙ›˜, Ô˘ ‰Ú‡ÂÈ ÛÙË µ·ÓÙÔ‡˙, §›¯ÙÂÓÛÙ·˚Ó. ∂˘¯·ÚÈÛٛ˜ ·¢ı‡ÓÔÓÙ·È Â›Û˘ ÛÙËÓ È·ÙÚfi ΢ڛ· ¶·Ó·ÁÈÒÙ· ª·ÓˆÏ¿ÎÔ˘ ÁÈ· ÙÔÓ „ËÊÈ·Îfi ۯ‰ȷÛÌfi Ù˘ ∂ÈÎfiÓ·˜ 1.

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29. Yan L, Yang X, Davidson NE. Role of DNA methylation and histone acetylation in steroid receptor expression in breast cancer. J Mammary Gland Biol Neoplasia 2001;6:183-192.

30. Schneider R, Bannister AJ, Kouzarides T. Unsafe SETs: histone lysine methyltransferases and cancer. Trends Biochem Sci 2002;27:396-402.

31. Kristiansen M, Helland A, Kristensen GB, Olsen AO, Lo/ nning PE, Bo/ rresen-Dale AL, et al. X chromosome inactivation in cervical cancer patients. Cancer Genet Cytogenet 2003;146:73-76.

32. Novelli M, Cossu A, Oukrif D, Quaglia A, Lakhani S, Poulsom R, et al. X-inactivation patch size in human female tissue confounds the assessment of tumor clonality. Proc Natl Acad Sci USA 2003;100:3311-3314.

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34. Kristiansen M, Langer A, Knudsen GP, Weber BL, Bo/ rresen-Dale A-L, O / rstavik KH. X chromosome inactivation pattern in female patients with breast cancer. Breast Cancer Res 2000;2:P1.10.

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37. Passarge E, Fries E. X chromosome inactivation in Xlinked hypohidrotic ectodermal dysplasia. Nature New Biol 1973;245:58-59.

38. O / rstavik KH, Knudsen GP, Nordgarden H, Ormerod E, Stro/ mme P, Lazarou LP, et al. Severe hypohidrotic ectodermal dysplasia in a girl caused by a de novo 9;X insertion that includes XIST and disrupts the EDA gene. Am J Med Genet A 2007;143A:1510-1513.

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41. Martin-Villa JM, Corell A, Ramos-Amador JT, Ruiz-Contreras J, Arnaiz-Villena A. Higher incidence of autoantibodies in X-linked chronic granulomatous disease carriers: random X-chromosome inactivation may be related to autoimmunity. Autoimmunity 1999;31:261-264.

42. Demura M, Takeda Y, Yoneda T, Furukawa K, Tachi A, Mabuchi H. Completely skewed X-inactivation in a mentally retarded young female with pseudohypoparathyroidism type IB and juvenile renin-dependent hypertension. J Clin Endocrinol Metab 2003;88:3043-3049.

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X-chromosome inactivation and ovarian age during the reproductive years. Fertil Steril 2006;85:1488-1495.

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ªÈÎÚÔÏÈı›·ÛË fiÚ¯ÂˆÓ ¢. £ˆÌ¿˜1,2, ∂. µÏ·¯Ô··‰ÔÔ‡ÏÔ˘2, µ. ¶··‰¿Î˘3 ¶ÂÚ›ÏË„Ë: ∏ ÌÈÎÚÔÏÈı›·ÛË ÙˆÓ fiÚ¯ÂˆÓ (ª√) Â›Ó·È ÌÈ· Û¯ÂÙÈο Û¿ÓÈ· ·ıÔÏÔÁÈ΋ ηٿÛÙ·ÛË ÛÙ· ·È‰È¿ Î·È ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÙËÓ ·ÚÔ˘Û›· ÌÈÎÚÔ·Û‚ÂÛÙÒÛÂˆÓ ÛÙÔ ÔÚ¯ÈÎfi ·Ú¤Á¯˘Ì·, ÔÈ Ôԛ˜ ·ÓȯÓ‡ÔÓÙ·È Û ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ˘ÂÚ˯ÔÁÚ¿ÊËÌ· fiÚ¯ÂˆÓ ÁÈ· ÔÈΛϘ ÂӉ›ÍÂȘ. ∂ÌÊ·Ó›˙ÂÈ ˘„ËÏfiÙÂÚÔ ÂÈÔÏ·ÛÌfi Û ·È‰È¿ Ì ÁÂÓÂÙÈο Û‡Ó‰ÚÔÌ· Î·È ¤¯ÂÈ Û˘Û¯ÂÙÈÛı› Ì ÙËÓ ÂÌÊ¿ÓÈÛË Î·ÏÔ‹ıˆÓ Î·È Î·ÎÔ‹ıˆÓ ÓÂÔÏ·ÛÈÒÓ, ÙfiÛÔ ÛÙÔ˘˜ fiÚ¯ÂȘ, fiÛÔ Î·È Û ¿ÏÏ· fiÚÁ·Ó·. ∞Ó Î·È Ô Ú·ÁÌ·ÙÈÎfi˜ ÂÈÔÏ·ÛÌfi˜ ‰ÂÓ Â›Ó·È ÁÓˆÛÙfi˜, ÛÙË ‰ÈÂıÓ‹ ‚È‚ÏÈÔÁÚ·Ê›· ·Ó·Ê¤ÚÔÓÙ·È ÔÛÔÛÙ¿ Ô˘ ·ÊÔÚÔ‡Ó ÌÂÁ¿ÏÔ ÏËı˘ÛÌfi ·ÛıÂÓÒÓ Ô˘ ˘Ô‚Ï‹ıËÎ·Ó Û ˘ÂÚ˯ÔÁÚ¿ÊËÌ· fiÚ¯ÂˆÓ Î·È Î˘Ì·›ÓÔÓÙ·È ·fi 0,6 ¤ˆ˜ 18,1% ÛÙÔ˘˜ ÂÓ‹ÏÈΘ Î·È ·fi 1,1-1,9% ÛÙ· ·È‰È¿. √ ÂÈÔÏ·ÛÌfi˜ ÙˆÓ Î·ÎÔËıÂÈÒÓ Î˘Ì·›ÓÂÙ·È ·fi 6-46% ÛÙÔ˘˜ ÂÓ‹ÏÈΘ Î·È ·fi 0-12,5% ÛÙ· ·È‰È¿. ∏ ÔÚ›· Ù˘ ª√ Û ·È‰È¿ ‰ÂÓ Â›Ó·È ÚԂϤ„ÈÌË Ì ·ÎÚ›‚ÂÈ·. ∞ÚÎÂÙ¤˜ ·Ó·ÊÔÚ¤˜ ‰Â›¯ÓÔ˘Ó ÙËÓ Ù¿ÛË ·Ó¿Ù˘Í˘ fiÁÎˆÓ ÛÙÔ˘˜ fiÚ¯ÂȘ ·ÛıÂÓÒÓ Ì ª√, ˘ÔÓÔÒÓÙ·˜ fiÙÈ ı· ÌÔÚÔ‡Û ӷ ·ÔÙÂÏ› ÚÔ-ηÚÎÈӈ̷ÙÒ‰Ë Î·Ù¿ÛÙ·ÛË. ¶ÂÚ›Ô˘ 8% ÙˆÓ ÂÚÈÙÒÛÂˆÓ ı· ·Ó·Ù‡ÍÔ˘Ó Î·ÎÔ‹ıÂÈ· Ù· ÂfiÌÂÓ· 6 ¯ÚfiÓÈ·, Û‡Ìʈӷ Ì ٷ ‰ËÌÔÛÈÂ˘Ì¤Ó· ÛÙÔȯ›·. ∏ Èı·ÓfiÙËÙ· Â›Ó·È Ë ›‰È· ÁÈ· Ù· ·È‰È¿ Î·È ÙÔ˘˜ ÂÓ‹ÏÈΘ, ·ÏÏ¿ ‰ÂÓ Â›Ó·È ÁÓˆÛÙ‹ Ë Èı·ÓfiÙËÙ· ηÎÔ‹ıÂÈ·˜ Û ̷ÎÚÔ¯ÚfiÓÈ· ·Ú·ÎÔÏÔ‡ıËÛË. √È Û˘ÛÙ¿ÛÂȘ ÁÈ· ÙËÓ ·Ú·ÎÔÏÔ‡ıËÛË ·È‰ÈÒÓ Ì ÌÂÌÔӈ̤ÓË ª√ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÂÙ‹ÛÈÔ ¤ÏÂÁ¯Ô Ì ˘ÂÚ˯ÔÁÚ¿ÊËÌ· fiگˆÓ, ÂÓı¿ÚÚ˘ÓÛË ÙˆÓ ÌÈÎÚÒÓ ·È‰ÈÒÓ ÁÈ· ·˘ÙÔÂͤٷÛË Ì ÙË ‚Ô‹ıÂÈ· ÙˆÓ ÁÔÓ¤ˆÓ ÙÔ˘˜ Î·È ÚÔÛÂÎÙÈ΋ ÎÏÈÓÈ΋ ÂͤٷÛË ·fi ÙÔ ıÂÚ¿ÔÓÙ· È·ÙÚfi.

1 ∂Ó‰ÔÎÚÈÓÔÏÔÁÈ΋ ∫ÏÈÓÈ΋, ∂∞¡¶ “ªÂÙ·Í¿”, ¶ÂÈÚ·È¿˜ 2 ∆Ì‹Ì· ∞‡ÍËÛ˘ Î·È ∞Ó¿Ù˘Í˘, °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ ∞ıËÓÒÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡” 3 ∆Ì‹Ì· ¶·È‰È·ÙÚÈ΋˜ ∞ÈÌ·ÙÔÏÔÁ›·˜-√ÁÎÔÏÔÁ›·˜, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “∏ ∞Á›· ™ÔÊ›·”, ∞ı‹Ó· AÏÏËÏÔÁÚ·Ê›·: ∂Ï›‰· µÏ·¯Ô··‰ÔÔ‡ÏÔ˘ elpis.vl@gmail.com. ∆Ì‹Ì· ∞‡ÍËÛ˘ Î·È ∞Ó¿Ù˘Í˘, °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ ∞ıËÓÒÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡” ªÂÛÔÁ›ˆÓ 24, ∆.∫. 115 27, ∞ı‹Ó·

§¤ÍÂȘ ÎÏÂȉȿ: ªÈÎÚÔÏÈı›·ÛË, fiÚ¯ÂȘ.

Testicular microlithiasis D. Thomas1,2, ∂. Vlahopapadopoulou2, V. Papadakis3 Abstract: Testicular microlithiasis (TM) is a relatively uncommon condition in the paediatric population, characterized by the presence of hyperechoic foci (microliths) within the testicular parenchyma, usually found incidentally in patients referred for scrotal ultrasound (U/S) for various reasons. It is encountered at a higher prevalence in children with genetic syndromes and has been associated with both benign and malignant lesions of the testes and other tissues. Although the true prevalence of TM in the population is still unknown, recent data on large series of patients who underwent scrotal U/S give ranges of 0.6 to 18.1% for the adult population and 1.1 to 1.9% for children. The natural history of TM cannot be predicted with precision. There have been several reports of testicular tumour development in patients with TM, indicating the possibility of it being a pre-malignant condition. ∆he reported rate of development of malignancy varies from 6-46% in adults and 0-12.5% in children. It has been estimated that almost 8% of subjects with TM will develop testicular tumour in the 6 years following identification. This probability is about the same for children and adults, but the long term risk of tumour development is not known at present. For the follow-up of children with isolated TM, annual U/S screening, regular careful self-examination and physical examination by a physician are highly recommended.

1 Department of Endocrinology, EANP “ªetaxa”, Piraeus 2 Department of Growth and Development, “P. & A. Kyriakou” Children’s Hospital, Athens, Greece 3 Department of Paediatric Haematology-Oncology, “Aghia Sophia” Children’s Hospital, Athens, Greece Correspondence: Elpida Vlahopapadopoulou elpis.vl@gmail.com Department of Growth and Development, “P. & A. Kyriakou” Children’s Hospital 24, Mesogion St. 115 27, Athens, Greece

Key words: Microlithiasis, testes.

∂ÈÛ·ÁˆÁ‹ ∏ ÌÈÎÚÔÏÈı›·ÛË fiÚ¯ÂˆÓ (ª√) Â›Ó·È ÌÈ· Û¯ÂÙÈο Û¿ÓÈ· ηٿÛÙ·ÛË, Ë ÔÔ›· ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÙËÓ ·ÚÔ˘Û›· ˘ÂÚ˯ÔÁÂÓÒÓ ÂÛÙÈÒÓ (ÌÈÎÚfiÏÈıÔÈ) ÂÓÙfi˜ ÙÔ˘ ÔÚ¯ÈÎÔ‡ ·ÚÂÁ¯‡Ì·ÙÔ˜, ‰È·Ì¤ÙÚÔ˘ ÌÈÎÚfiÙÂÚ˘ ÙˆÓ 1-2 mm Î·È Û˘Ó‹ıˆ˜ ·Ó·ÁÓˆÚ›˙ÂÙ·È Û ·ÛıÂÓ›˜ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û ˘ÂÚ˯ÔÁÚ¿ÊËÌ· fiÚ-

¯ÂˆÓ ÁÈ· ‰È¿ÊÔÚÔ˘˜ ÏfiÁÔ˘˜. √È ÌÈÎÚÔ·Û‚ÂÛÙÒÛÂȘ ‚Ú›ÛÎÔÓÙ·È Î˘Ú›ˆ˜ ̤۷ ÛÙ· ÛÂÚÌ·ÙÈο ÛˆÏËÓ¿ÚÈ· ÙÔ˘ fiگˆ˜ Î·È ÌÔÚ› Ó· Û˘Ó‰˘¿˙ÔÓÙ·È Ì ηÏÔ‹ıÂȘ Î·È Î·ÎÔ‹ıÂȘ ‚Ï¿‚˜ ÛÙÔ˘˜ fiÚ¯ÂȘ ‹ Û ¿ÏÏÔ˘˜ ÈÛÙÔ‡˜ (1). ¢ÂÓ ¤¯ÂÈ ·ÎfiÌ· ‰È¢ÎÚÈÓÈÛÙ› ·Ó ·Ï¿ Û˘Ó˘¿Ú¯ÂÈ Ì ¿ÏϘ ·ıÔÏÔÁÈΤ˜ ηٷÛÙ¿ÛÂȘ ‹ ·Ó Úԉȷı¤ÙÂÈ ÙËÓ ·Ó¿Ù˘ÍË ÛÔ‚·ÚfiÙÂÚˆÓ ¶·È‰È·ÙÚÈ΋ 2008;71:277-282

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∂ÈÎfiÓ· 1. ÀÂÚ˯ÔÁÚ¿ÊËÌ· fiÚ¯ÂˆÓ ‰‡Ô ·‰ÂÏÊÒÓ Ì ÌÈÎÚÔÏÈı›·ÛË fiگˆÓ.

1, 2: √È ÂÈÎfiÓ˜ ·Ó‹ÎÔ˘Ó ÛÙÔ ÌÂÁ·Ï‡ÙÂÚ˘ ËÏÈΛ·˜ ·‰ÂÏÊfi Î·È Î·Ù·‰ÂÈÎÓ‡Ô˘Ó ‰È¿Û·ÚÙÔ˘˜ ÌÈÎÚfiÏÈıÔ˘˜, ¯ˆÚ›˜ ·ÎÔ˘ÛÙÈ΋ ÛÎÈ¿, ÌÂ Û˘ÌÌÂÙÚÈ΋ ηٷÓÔÌ‹ ÛÙÔ ÔÚ¯ÈÎfi ·Ú¤Á¯˘Ì·.

3, 4: √È ÂÈÎfiÓ˜ ·Ó‹ÎÔ˘Ó ÛÙÔ ÌÈÎÚfiÙÂÚ˘ ËÏÈΛ·˜ ·‰ÂÏÊfi Î·È Î·Ù·‰ÂÈÎÓ‡Ô˘Ó ÏÈÁfiÙÂÚÔ ˘ÎÓfi ÚfiÙ˘Ô ·Û‡ÌÌÂÙÚ˘ ηٷÓÔÌ‹˜ ÙˆÓ ÌÈÎÚÔ·Û‚ÂÛÙÒÛÂˆÓ ÛÙÔ ·Ú¤Á¯˘Ì· ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ fiگˆ˜. ™ÙÔ ‰ÂÍÈfi fiÚ¯È ‰ÂÓ ·Ó·ÁÓˆÚ›˙ÔÓÙ·È ÌÈÎÚfiÏÈıÔÈ. (∞fi ÙÔ ·Ú¯Â›Ô ÙÔ˘ ∆Ì‹Ì·ÙÔ˜ ∞‡ÍËÛ˘ Î·È ∞Ó¿Ù˘Í˘, Ì ÙËÓ ¤ÁÁÚ·ÊË Û˘ÁηٿıÂÛË ÙˆÓ ÁÔÓ¤ˆÓ ÁÈ· ·ÓÒÓ˘ÌË ‰ËÌÔÛ›Â˘ÛË Ù˘ ˘ÂÚ˯ÔÁÚ·ÊÈ΋˜ ÂÈÎfiÓ·˜).

·ı‹ÛˆÓ. ∞ÛıÂÓ›˜ ÛÙÔ˘˜ ÔÔ›Ô˘˜ Ë ª√ ·Ó·Î·Ï‡ÙÂÙ·È Ù˘¯·›·, Û˘Ó‹ıˆ˜ ‰ÈÂÚ¢ÓÒÓÙ·È ÂÚ·ÈÙ¤Úˆ Ì ηÚÎÈÓÈÎÔ‡˜ ‰Â›ÎÙ˜, ·ÂÈÎÔÓÈÛÙÈΤ˜ ÂÍÂÙ¿ÛÂȘ Î·È Èı·ÓÒ˜ Ì ‚ÈÔ„›·, ÂÓÒ ·Ú·ÎÔÏÔ˘ıÔ‡ÓÙ·È Ì·ÎÚÔ¯ÚfiÓÈ· Ì ÎÏÈÓÈ΋ ÂͤٷÛË Î·È ˘ÂÚ˯ÔÁÚ·ÊÈÎfi ¤ÏÂÁ¯Ô (2). ªÂ ‰Â‰Ô̤ÓÔ fiÙÈ Ô Û˘ÓÔÏÈÎfi˜ ·ÚÈıÌfi˜ ÙˆÓ ‰ËÌÔÛÈÂ˘Ì¤ÓˆÓ ·È‰È·ÙÚÈÎÒÓ ÂÚÈÛÙ·ÙÈÎÒÓ Â›Ó·È ÂÚÈÔÚÈṲ̂ÓÔ˜, ·ÚÔ˘ÛÈ¿˙ÂÙ·È ·Ó·ÛÎfiËÛË Ù˘ Û¯ÂÙÈ΋˜ ‚È‚ÏÈÔÁÚ·Ê›·˜ Ì ¤ÌÊ·ÛË ÛÙËÓ Â›ÙˆÛË, ÙË Ê˘ÛÈ΋ ÈÛÙÔÚ›·, ÙȘ Û¯ÂÙÈ˙fiÌÂÓ˜ ηٷÛÙ¿ÛÂȘ Î·È ÙËÓ ·Ú·ÎÔÏÔ‡ıËÛË ·ÛıÂÓÒÓ Ì ÌÈÎÚÔÏÈı›·ÛË fiگˆÓ.

Û˘ÁÎÂÓÙÚÈΤ˜ ÛÙÈ‚¿‰Â˜ ÎÔÏÏ·ÁfiÓÔ˘ Î·È ÁÏ˘ÎÔÚˆÙÂ˚ÓÒÓ, ÔÈ Ôԛ˜ ηχÙÔÓÙ·È ·fi ÂÓ·Ôı¤ÛÂȘ ·Û‚ÂÛÙ›Ô˘. ™ÙÔ ‰Â‡ÙÂÚÔ Ù‡Ô, ÔÈ ·Û‚ÂÛÙÒÛÂȘ Û¯ËÌ·Ù›˙Ô˘Ó ¿ÌÔÚÊ· ۈ̿ÙÈ· (ηٿÏÔÈ·), Ù· ÔÔ›· ‰›ÓÔ˘Ó ıÂÙÈ΋ ¯ÚÒÛË ·ÈÌ·ÙÔÍ˘Ï›Ó˘. √ Ù‡Ô˜ ·˘Ùfi˜ Û¯ÂÙ›˙ÂÙ·È Ì fiÁÎÔ˘˜ ·Ú¯¤ÁÔÓˆÓ ÁÂÓÓËÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ (germ cell tumors) Î·È ÈÛÙ‡ÂÙ·È fiÙÈ Â›Ó·È ·ÔÙ¤ÏÂÛÌ· ÙÔ˘ ÁÚ‹ÁÔÚÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙÔ˘ ·Û‚ÂÛÙ›Ô˘ ÛÙ· ·ÙÙ·Ú· ÙÔ˘ fiÁÎÔ˘. ¶ÚfiÛÊ·Ù· ‰Â‰Ô̤ӷ ÂÓÈÛ¯‡Ô˘Ó ÙËÓ ˘fiıÂÛË fiÙÈ ÔÈ ÌÈÎÚÔ·Û‚ÂÛÙÒÛÂȘ ÌÔÚ› Ó· ÚÔ¤Ú¯ÔÓÙ·È ·fi “ÔÏ˘ÂÛÙȷ΋” ‰˘ÛÏÂÈÙÔ˘Á›· ÙˆÓ Î˘ÙÙ¿ÚˆÓ Sertoli (5).

πÛÙÔÏÔÁ›· ∏ ª√ ‰È·ÎÚ›ÓÂÙ·È Û ‰‡Ô ͯˆÚÈÛÙÔ‡˜ ÈÛÙÔÏÔÁÈÎÔ‡˜ Ù‡Ô˘˜ (3). √ ÚÒÙÔ˜ ·ÊÔÚ¿ ·Û‚ÂÛÙÒÛÂȘ Û˘Ó‰ÂÙÈÎÔ‡ ÈÛÙÔ‡, ÔÈ Ôԛ˜ ÚÔ¤Ú¯ÔÓÙ·È ·fi ÂÎʇÏÈÛË Î·È ·fiÙˆÛË ÙÔ˘ ÛÂÚÌ·ÙÈÎÔ‡ ÂÈıËÏ›Ô˘ ̤۷ ÛÙÔÓ ·˘Ïfi ÙˆÓ ÔÚ¯ÈÎÒÓ ÛˆÏËÓ·Ú›ˆÓ (4). ∆· ηٿÏÔÈ· ÙÔ˘ ÂÈıËÏ›Ô˘ Ô˘ ΛÙÔÓÙ·È ÂÓÙfi˜ ÙÔ˘ ·˘ÏÔ‡ ÙˆÓ ÛˆÏËÓ·Ú›ˆÓ Û˘ÛÛˆÚ‡ÔÓÙ·È ¿Óˆ ÛÂ

ÀÂÚ˯ÔÁÚ·ÊÈ΋ ·ÂÈÎfiÓÈÛË ∏ ÎÏ·ÛÈ΋ ˘ÂÚ˯ÔÁÚ·ÊÈ΋ ÂÈÎfiÓ· Ù˘ ª√ ηٷ‰ÂÈÎÓ‡ÂÈ ÔÏÏ·ÏÔ‡˜ ÌÈÎÚfiÏÈıÔ˘˜ (˘ÂÚ˯ÔÁÂÓ›˜, ÛÙÈÎÙ¤˜ ÂÛٛ˜, ‰È·Ì¤ÙÚÔ˘ 1-2 mm, ÂÚÈÛÛfiÙÂÚ˜ ·fi 5 ·Ó¿ ÔÙÈÎfi ‰›Ô), ¯ˆÚ›˜ ·ÎÔ˘ÛÙÈ΋ ÛÎÈ¿, ÔÈ ÔÔ›ÔÈ ‚Ú›ÛÎÔÓÙ·È ‰È¿Û·ÚÙÔÈ ÛÙÔ ÔÚ¯ÈÎfi ·Ú¤Á¯˘Ì·, Û˘Ó‹ıˆ˜ ÌÂ Û˘ÌÌÂÙÚÈÎfi ÚfiÙ˘Ô ÂÌÊ¿ÓÈÛ˘ (∂ÈÎfiÓ· 1).

Paediatriki 2008;71:277-282

Pediatri Jul-Aug 08

30-07-08

15:52

™ÂÏ›‰·279

279

% ÔÛÔÛÙfi ÙˆÓ ·ÛıÂÓÒÓ

ªÈÎÚÔÏÈı›·ÛË fiگˆÓ

20 18 16 14 12 10 8 6 4 2 0

∞ÛıÂÓ›˜ Ì ª√ ∞ÛıÂÓ›˜ Ì ª√ Î·È fiÁÎÔ˘˜ fiگˆÓ

8

9

10

11

12

13

14

15

16

17

18

∂ÈÎfiÓ· 2. ƒ·‚‰fiÁÚ·ÌÌ· Ô˘ ‰Â›¯ÓÂÈ ÙË Û˘¯ÓfiÙËÙ· Ù˘ ª√ Î·È Ù˘ Û˘Ó‡·Ú͢ ª√ Î·È fiÁÎˆÓ fiÚ¯ÂˆÓ Û ·È‰È¿ (17,18) Î·È Û ÌÈÎÙÔ‡˜ ÏËı˘ÛÌÔ‡˜ ·È‰ÈÒÓ-ÂÓËÏ›ÎˆÓ (8-16). √È ·ÚÈıÌÔ› ÛÙÔÓ ÔÚÈ˙fiÓÙÈÔ ¿ÍÔÓ· ÙÔ˘ ‰È·ÁÚ¿ÌÌ·ÙÔ˜ ·Ú·¤ÌÔ˘Ó ÛÙȘ ·ÓÙ›ÛÙÔȯ˜ ‚È‚ÏÈÔÁÚ·ÊÈΤ˜ ·Ó·ÊÔÚ¤˜.

∫ÏËÚÔÓÔÌÈÎfiÙËÙ· ¶ÚÔ˜ ÙÔ ·ÚfiÓ, ‰ÂÓ ¤¯ÂÈ ‰È¢ÎÚÈÓÈÛÙ› ·Ó ˘¿Ú¯ÂÈ ÎÏËÚÔÓÔÌÈ΋ ÚԉȿıÂÛË ÁÈ· ÙË ÌÈÎÚÔÏÈı›·ÛË ÙˆÓ fiگˆÓ. ªÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ ÁÔÓ›‰ÈÔ SLC34A2 (6) ÙÔ˘ Ù‡Ô˘-IIb Û˘ÌÌÂÙ·ÊÔÚ¤· Na-P, ÙÔ ÔÔ›Ô Â˘ı‡ÓÂÙ·È ÁÈ· ÙËÓ Ó¢ÌÔÓÈ΋ ÌÈÎÚÔÏÈı›·ÛË Î·È ÔÌÔ˙˘ÁˆÙ›· ÁÈ· ÙË “ÛȈËÏ‹” ÌÂÙ¿ÏÏ·ÍË Lys463X ÙÔ˘ ÁÔÓȉ›Ô˘ GALNT3 (7) Ô˘ Â›Ó·È ˘‡ı˘ÓÔ ÁÈ· ÙÔ Û‡Ó‰ÚÔÌÔ Ù˘ ÔÈÎÔÁÂÓÔ‡˜ ηÎÔ‹ıÔ˘˜ ·Û‚ÂÛÙÒÛˆ˜, ·ÓȯÓ‡ÔÓÙ·È Û˘¯Ó¿ Û ·ÛıÂÓ›˜ Ì ª√. ¡ÂÔϷۛ˜ Î·È ª√ ∞Ó Î·È Ë ·ÏËı‹˜ Â›ÙˆÛË Ù˘ ª√ ÛÙÔ ÁÂÓÈÎfi ÏËı˘ÛÌfi ‰ÂÓ Â›Ó·È ÁÓˆÛÙ‹, ÚfiÛÊ·Ù· ‰ËÌÔÛÈÂ˘Ì¤Ó· ‰Â‰Ô̤ӷ ·fi ÌÂÁ¿Ï˜ ÛÂÈÚ¤˜ ·ÛıÂÓÒÓ Ô˘ ˘Ô‚Ï‹ıËÎ·Ó Û ˘ÂÚ˯ÔÁÚ¿ÊËÌ· fiÚ¯ÂˆÓ ·Ó·Ê¤ÚÔ˘Ó ÔÛÔÛÙ¿ ·fi 0,6 ¤ˆ˜ 18,1% ÛÙÔ˘˜ ÂÓ‹ÏÈΘ (816) Î·È ·fi 1,1 ¤ˆ˜ 1,9% ÛÙ· ·È‰È¿ (17,18). √ÏÔ¤Ó· Î·È ÂÚÈÛÛfiÙÂÚ˜ ‰ËÌÔÛȇÛÂȘ Û˘Û¯ÂÙ›˙Ô˘Ó ÙË ª√ Ì fiÁÎÔ˘˜ ÙˆÓ fiگˆÓ. √ ÂÈÔÏ·ÛÌfi˜ ηÎÔ‹ıˆÓ ·ı‹ÛÂˆÓ ÙˆÓ fiÚ¯ÂˆÓ Û ·ÛıÂÓ›˜ Ì ª√ Î˘Ì·›ÓÂÙ·È ·fi 6 ¤ˆ˜ 46% ÛÙÔ˘˜ ÂÓ‹ÏÈΘ Î·È ·fi 0 ¤ˆ˜ 12,5% ÛÙ· ·È‰È¿ (∂ÈÎfiÓ· 2). √ ˘„ËÏfiÙÂÚÔ˜ ÂÈÔÏ·ÛÌfi˜ ÛÙÔ˘˜ ÂÓ‹ÏÈΘ ÚÔÊ·ÓÒ˜ ·ÓÙÈηÙÔÙÚ›˙ÂÈ ÙÔ ÌÂÁ·Ï‡ÙÂÚÔ ¯ÚÔÓÈÎfi ‰È¿ÛÙËÌ· ¤ÎıÂÛ˘ ÙˆÓ ·ÙfiÌˆÓ Û ÚԉȷıÂÛÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜, ·ÊÔ‡ Ë Èı·ÓfiÙËÙ· ·Ó¿Ù˘Í˘ ÓÂÔÏ·Û›·˜ fiÚ¯ÂˆÓ Û ·ÛıÂÓ›˜ Ì ª√ Û ‚Ú·¯˘¯ÚfiÓÈ· ‰È·ÛÙ‹Ì·Ù· ·Ú·ÎÔÏÔ‡ıËÛ˘ Â›Ó·È ÂÚ›Ô˘ Ë ›‰È· ÁÈ· ·È‰È¿ Î·È ÂÓ‹ÏÈΘ, fiˆ˜ ı· ·Ó·ÊÂÚı› ·Ú·Î¿Ùˆ. ∏ ÔÚ›· Ù˘ ª√ Û ·È‰È¿ ‰ÂÓ Â›Ó·È ÚԂϤ„ÈÌË Ì ·ÎÚ›‚ÂÈ·. ∞ÚÎÂÙ¤˜ ·Ó·ÊÔÚ¤˜ ‰Â›¯ÓÔ˘Ó ÙËÓ Ù¿ÛË ·Ó¿Ù˘Í˘ fiÁÎˆÓ ÛÙÔ˘˜ fiÚ¯ÂȘ ·ÛıÂÓÒÓ Ì ª√, ˘ÔÓÔÒÓÙ·˜ fiÙÈ ı· ÌÔÚÔ‡Û ӷ ·ÔÙÂÏ› ÚÔ-ηÚ-

ÎÈӈ̷ÙÒ‰Ë Î·Ù¿ÛÙ·ÛË. Œ¯ÂÈ ÚÔÙ·ı› fiÙÈ Ë ª√ Î·È ÔÈ ÓÂÔϷۛ˜ ÙˆÓ fiÚ¯ÂˆÓ Â›Ó·È Èı·Ófi Ó· ÚÔηÏÔ‡ÓÙ·È ·fi ÎÔÈÓfi ·›ÙÈÔ, fiˆ˜ Ë ÂÎʇÏÈÛË ÙˆÓ ÔÚ¯ÈÎÒÓ ÛˆÏËÓ·Ú›ˆÓ, ÂÓÒ ‰ÂÓ ÌÔÚ› Ó· ·ÔÎÏÂÈÛÙ› ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ë ª√ Â›Ó·È ÚÒÈÌË ÂΉ‹ÏˆÛË Ù˘ ÓÂÔÏ·Û›·˜. ∞Ó Î·È Ô ‰ËÌÔÛÈÂ˘Ì¤ÓÔ˜ ·ÚÈıÌfi˜ ·È‰ÈÒÓ Ì ª√ Ô˘ ›¯·Ó ‚Ú·¯˘¯ÚfiÓÈ· ·Ú·ÎÔÏÔ‡ıËÛË Â›Ó·È ÌÈÎÚfi˜, Ê·›ÓÂÙ·È fiÙÈ Ôχ ÌÈÎÚfi ÔÛÔÛÙfi ·fi Ù· ·È‰È¿ ·˘Ù¿ ı· ·Ó·Ù‡ÍÂÈ fiÁÎÔ ÛÙÔ˘˜ fiÚ¯ÂȘ Ù· ÂfiÌÂÓ· 7 ¯ÚfiÓÈ· (11-14,18,19-26) Î·È Ë Èı·ÓfiÙËÙ· ·Ú·Ì¤ÓÂÈ Ë ›‰È· ÁÈ· ·È‰È¿ Î·È ÂÓ‹ÏÈΘ. ∏ Èı·ÓfiÙËÙ· ·Ó¿Ù˘Í˘ ÓÂÔÏ·Û›·˜ Û ·ÒÙÂÚÔ ¯ÚfiÓÔ Î·È ÁÈ· ÌÂÁ·Ï‡ÙÂÚ· ¯ÚÔÓÈο ‰È·ÛÙ‹Ì·Ù· ·Ú·ÎÔÏÔ‡ıËÛ˘ ‰ÂÓ Â›Ó·È ÁÓˆÛÙ‹.

™˘ÓÔ‰¤˜ ·ı‹ÛÂȘ ¡ÂÔϷۛ˜ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ª√ ›ӷÈ: fiÁÎÔÈ ÏÂÎÈıÈÎÔ‡ ·ÛÎÔ‡ (27), ÛÂ̛ӈ̷ (28), ÂÌ‚Ú˘ÔÓÈÎfi ηÚΛӈ̷ (29) Î·È ÌÈÎÙfi˜ fiÁÎÔ˜ ·Ú¯¤ÁÔÓˆÓ ÁÂÓÓËÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ (30). ∂ÈϤÔÓ, ÌÔÚ› Ó· Û¯ÂÙ›˙ÂÙ·È Ì Â͈-ÔÚ¯ÈÎÔ‡˜ fiÁÎÔ˘˜ Ô˘ ÂÓÙÔ›˙ÔÓÙ·È ÛÙÔ ÌÂÛÔıˆÚ¿ÎÈÔ, fiˆ˜ ÙÂڿو̷ (31), fiÁÎÔÈ ·Ú¯¤ÁÔÓˆÓ ÁÂÓÓËÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ (32), ÛÂ̛ӈ̷ (33) Î·È ¯ÔÚÈÔηÚΛӈ̷ (34). °È· Ù· ·È‰È¿ Ì ª√ Î·È fiÁÎÔ ÛÙÔÓ ›‰ÈÔ ‹ ÛÙÔÓ ÂÙÂÚfiÏ¢ÚÔ ÔÚ¯ÈÎfi ÈÛÙfi, ı· Ú¤ÂÈ Ó· Ï·Ì‚¿ÓÂÙ·È ˘fi„Ë fiÙÈ ÔÈ Û‡ÛÙÔȯÔÈ fiÁÎÔÈ ·ÔÙÂÏÔ‡Ó Î›Ó‰˘ÓÔ ÁÈ· ÙËÓ ·Ó¿Ù˘ÍË fiÁÎÔ˘ ÛÙÔÓ ÂÙÂÚfiÏ¢ÚÔ fiÚ¯È (35) Î·È fiÙÈ Ë ÂÓ‰ÔÛˆÏËÓ·Úȷ΋ ÓÂÔÏ·Û›· ÌÔÚ› Ó· ÂÍÂÏȯı› Û ‰ÈËıËÙÈÎfi fiÁÎÔ Ì Èı·ÓfiÙËÙ· 50% Û 5 ¯ÚfiÓÈ· (36). ∏ Èı·ÓfiÙËÙ· Û˘Ó‡·Ú͢ fiÁÎÔ˘ ÛÙÔ˘˜ fiÚ¯ÂȘ ‰ÂÓ Â›Ó·È Ë ÌÔÓ·‰È΋ ÓfiÛÔ˜ Ô˘ ı· Ú¤ÂÈ Ó· ·ÔÎÏÂÈÛÙ› Û ·È‰È¿ Ì ª√. ÕÏϘ ÓfiÛÔÈ Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ª√ Â›Ó·È Ù· Û‡Ó‰ÚÔÌ· Down (37), McCune-Albright (38), Frasier (39) Î·È Klinefelter, Ë Î˘ÛÙÈ΋ ›ÓˆÛË (41), ÙÔ „¢‰ÔÍ¿ÓıˆÌ· elasticum (42), Ë ·Ó¿Ù˘ÍË ·ÓÙÈÛÂÚÌ·ÙÈÎÒÓ ·ÓÙÈÛˆÌ¿ÙˆÓ ‡ÛÙÂÚ· ·fi ‚ÈÔ„›· Û ·È‰È¿ Ì ÎÚ˘„ÔÚ¯›· (43), Ë Û˘ÛÙÚÔÊ‹ fiگˆ˜ Î·È Ó¤ÎÚˆÛË (44), Ë ÎÈÚÛÔ΋ÏË, Ë Âȉȉ˘Ì›Ùȉ·, Ë Ó¢ÚÔ˚ӈ̿وÛË Î·È ÙÔ AIDS (25). ∫¿ÔȘ ·fi ÙȘ ·ı‹ÛÂȘ ·˘Ù¤˜, fiˆ˜ Ë ÎÚ˘„ÔÚ¯›· Î·È Ë ·ÙÚÔÊ›·, Û¯ÂÙ›˙ÔÓÙ·È Ì ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ·Ó¿Ù˘Í˘ ηÎÔ‹ıÂÈ·˜, ·ÓÂÍ¿ÚÙËÙ· ·fi ÙËÓ ·ÚÔ˘Û›· ª√. ∞Ó Î·È ÙÔ ÂӉ¯fiÌÂÓÔ Ë ª√ Ó· ·ÚÈÛÙ¿ ÙËÓ ÚÒÙË ÂΉ‹ÏˆÛË Ù¤ÙÔÈˆÓ ÓÔÛËÌ¿ÙˆÓ Â›Ó·È Ôχ ÌÈÎÚfi, ÙÔ È·ÙÚÈÎfi ÈÛÙÔÚÈÎfi Î·È Ë ÚÔÛÂÎÙÈ΋ ÎÏÈÓÈ΋ ÂͤٷÛË ÂÈ‚¿ÏÏÔÓÙ·È. ¶·Ú·ÎÔÏÔ‡ıËÛË √È Û˘ÛÙ¿ÛÂȘ ÁÈ· ÙËÓ ·Ú·ÎÔÏÔ‡ıËÛË ·È‰ÈÒÓ Ì ÌÂÌÔӈ̤ÓË ª√ ÂÚÈÏ·Ì‚¿ÓÔ˘Ó ÂÙ‹ÛÈÔ ¤ÏÂÁ¯Ô Ì ˘ÂÚ˯ÔÁÚ¿ÊËÌ· fiگˆÓ, ÂÓı¿ÚÚ˘ÓÛË ÙˆÓ ÌÈÎÚÒÓ ¶·È‰È·ÙÚÈ΋ 2008;71:277-282

Pediatri Jul-Aug 08

30-07-08

15:52

™ÂÏ›‰·280

280

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·È‰ÈÒÓ ÁÈ· ·˘ÙÔÂͤٷÛË Ì ÙË ‚Ô‹ıÂÈ· ÙˆÓ ÁÔÓ¤ˆÓ ÙÔ˘˜ Î·È ÚÔÛÂÎÙÈ΋ ÎÏÈÓÈ΋ ÂͤٷÛË ·fi ÙÔ ıÂÚ¿ÔÓÙ· È·ÙÚfi. ∞Ó Î·È ÙÔ ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ¤¯ÂÈ ÌÂÁ·Ï‡ÙÂÚË Â˘·ÈÛıËÛ›· ·Ó›¯Ó¢Û˘ ÌÈ·˜ Ì¿˙·˜ ÚÈÓ Á›ÓÂÈ „ËÏ·ÊËÙ‹, Ë ·˘ÙÔÂͤٷÛË ıˆÚÂ›Ù·È ··Ú·›ÙËÙË, ÂȉÈο ·Ó ˘¿Ú¯ÂÈ ˘Ô„›· Ì¿˙·˜ Ô˘ ÌÂÁ·ÏÒÓÂÈ ÁÚ‹ÁÔÚ·. ∂ȉÈÎÔ› È·ÙÚÔ› ‰ÂÓ ıˆÚÔ‡Ó ÙËÓ ÂÚÈÔ‰È΋ ˘ÂÚ˯ÔÁÚ·ÊÈ΋ ÂͤٷÛË ·Ó·Áη›·, ÁÈ·Ù› Ù· ÔÛÔÛÙ¿ ›·Û˘ ÁÈ· ÙÔ˘˜ fiÁÎÔ˘˜ ·fi ·Ú¯¤ÁÔÓ· ÁÂÓÓËÙÈο ·ÙÙ·Ú· Â›Ó·È ˘„ËÏ¿, ·ÓÂÍ¿ÚÙËÙ· ·fi ÙÔ ÛÙ¿‰ÈÔ ÙÔ˘ fiÁÎÔ˘. ¶·Ú’ fiÏ· ·˘Ù¿, ÙÔ ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ·ÔÙÂÏ› ÊıËÓ‹, ·ÍÈfiÈÛÙË Î·È Â‡ÎÔÏ· ÚÔÛ‚¿ÛÈÌË ÂͤٷÛË, ¯ˆÚ›˜ ÂÈ‚¿Ú˘ÓÛË ÁÈ· Ù· ·È‰È¿ Î·È ÙÔ˘˜ ÂÊ‹‚Ô˘˜. ∏ ̤ÙÚËÛË Î·ÚÎÈÓÈÎÒÓ ‰ÂÈÎÙÒÓ, fiˆ˜ Ë ·ÂÌ‚Ú˘˚΋ ÚˆÙ½ÓË (·-FP), Ë ¯ÔÚÈÔÓÈ΋ ÁÔÓ·‰ÔÙÚÔ›ÓË (‚-hCG), ηıÒ˜ Î·È Ë ˘ÔÏÔÁÈÛÙÈ΋ ÙÔÌÔÁÚ·Ê›· ‹ MRI ÂÏ¿ÛÛÔÓÔ˜ ˘¤ÏÔ˘ Î·È ÎÔÈÏ›·˜ ‰ÂÓ Û˘ÛÙ‹ÓÔÓÙ·È ÁÈ· fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓ›˜ (11,46), ·Ú¿ ÌfiÓÔ ÁÈ· ÙËÓ ·Ú·ÎÔÏÔ‡ıËÛË fiÁÎˆÓ Ì Â͈-ÔÚ¯È΋ Â¤ÎÙ·ÛË Î·È ˘ÔÙÚÔ¤˜ ‹ ÌÂÙ·ÛÙ¿ÛÂȘ. ∞Ó Î·È Ë ‚ÈÔ„›· ÙˆÓ fiÚ¯ÂˆÓ ‰ÂÓ Û˘ÛÙ‹ÓÂÙ·È, ÏfiÁˆ ÙÔ˘ ÛËÌ·ÓÙÈÎÔ‡ ÔÛÔÛÙÔ‡ „¢‰Ò˜ ·ÚÓËÙÈÎÒÓ ·ÔÙÂÏÂÛÌ¿ÙˆÓ (47), ÔÈ ÔÏÏ·Ϥ˜ ‚ÈÔ„›Â˜ ÂӉ›ÎÓ˘ÓÙ·È (48) Û ·ÛıÂÓ›˜ Ì ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ·Ó¿Ù˘Í˘ fiÁÎÔ˘ fiگˆÓ, fiˆ˜ ·˘ÙÔ› Ì ÌÈÎÚÔ‡˜ Î·È ·ÙÚÔÊÈÎÔ‡˜ fiÚ¯ÂȘ ‹ ·ÛıÂÓ›˜ Ì ÎÚ˘„ÔÚ¯›·. ∂›Û˘, Ë ‚ÈÔ„›· (‰ÈÂÁ¯ÂÈÚËÙÈ΋, Ì ÙË ¯Ú‹ÛË ˘ÂÚ‹¯ˆÓ) ÂӉ›ÎÓ˘Ù·È ÛÙȘ ÂÚÈÙÒÛÂȘ ·ÛıÂÓÒÓ Ô˘ ˘Ô‚¿ÏÏÔÓÙ·È Û Â¤Ì‚·ÛË Û˘ÓÔ‰ÒÓ ·ı‹ÛˆÓ, fiˆ˜ ÎÚ˘„ÔÚ¯›·, ˘‰ÚÔ΋ÏË ‹ ÎÈÚÛÔ΋ÏË.

µÈ‚ÏÈÔÁÚ·Ê›· 1. Miller FN, Sidhu PS. Does testicular microlithiasis matter? A review. Clin Radiol 2002;57:883-890.

2. Dell’Acqua A, Tomà P, Oddone M, Ciccone MA, Marsili E, Derchi LE. Testicular microlithiasis: US findings in six pediatric cases and literature review. Eur Radiol 1999;9:940-944.

3. Renshaw AA. Testicular calcifications: incidence, histology and proposed pathological criteria for testicular microlithiasis. J Urol 1998;160:1625-1628.

4. Weinberg AG, Currarino G, Stone IC Jr. Testicular microlithiasis. Arch Pathol 1973;95:312-314.

5. Drut R, Drut RM. Testicular microlithiasis: histologic and immunohistochemical findings in 11 pediatric cases. Pediatr Dev Pathol 2002;5:544-550.

6. Corut A, Senyigit A, Ugur SA, Altin S, Ozcelik U, Calisir H, et al. Mutations in SLC34A2 cause pulmonary alveolar microlithiasis and are possibly associated with testicular microlithiasis. Am J Hum Genet 2006;79:650-656.

7. Campagnoli MF, Pucci A, Garelli E, Carando A, Defilippi C, Lala R, et al. Familial tumoral calcinosis and testicular microlithiasis associated with a new mutation of GALNT3 in a white family. J Clin Pathol 2006;59:440-442.

8. Cast JE, Nelson WM, Early AS, Biyani S, Cooksey G, Warnock NG, et al. Testicular microlithiasis: prevalence and tumor risk in a population referred for scrotal sonography.

AJR Am J Roentgenol 2000;175:1703-1706.

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9. Otite U, Webb JA, Oliver RT, Badenoch DF, Nargund VH. Testicular microlithiasis: is it a benign condition with malignant potential? Eur Urol 2001;40:538-542.

10. Skyrme RJ, Fenn NJ, Jones AR, Bowsher WG. Testicular microlithiasis in a UK population: its incidence, associations and follow-up. BJU Int 2000;86:482-485.

11. Pourbagher MA, Kilinc F, Guvel S, Pourbagher A, Egilmez T, Ozkardes H. Follow-up of testicular microlithiasis for subsequent testicular cancer development. Urol Int 2005;74:108-112.

12. Derogee M, Bevers RF, Prins HJ, Jonges TG, Elbers FH, Boon TA. Testicular microlithiasis, a premalignant condition: prevalence, histopathologic findings, and relation to testicular tumor. Urology 2001;57:1133-1137.

13. Bach AM, Hann LE, Hadar O, Shi W, Yoo HH, Giess CS, et al. Testicular microlithiasis: what is its association with testicular cancer? Radiology 2001;220:70-75.

14. Sakamoto H, Shichizyou T, Saito K, Okumura T, Ogawa Y, Yoshida H, et al. Testicular microlithiasis identified ultrasonographically in Japanese adult patients: prevalence and associated conditions. Urology 2006;68:636-641.

15. Höbarth K, Susani M, Szabo N, Kratzik C. Incidence of testicular microlithiasis. Urology 1992;40:464-467.

16. Middleton WD, Teefey SA, Santillan CS. Testicular microlithiasis: prospective analysis of prevalence and associated tumor. Radiology 2002;224:425-428.

17. Aso C, Enr›quez G, Fité M, Toraãn N, Pirfi C, Piqueras J, et al.

Gray-scale and color Doppler sonography of scrotal disorders in children: an update. Radiographics 2005;25:1197-1214.

18. Leenen AS, Riebel TW. Testicular microlithiasis in children: sonographic features and clinical implications. Pediatr Radiol 2002;32:575-579.

19. Dagash H, Mackinnon EA. Testicular microlithiasis: what does it mean clinically? BJU Int 2007;99:157-160.

20. Furness PD 3rd, Husmann DA, Brock JW 3rd, Steinhardt GF, Bukowski TP, Freedman AL, et al. Multi-institutional study of testicular microlithtiasis in childhood: a benign or premalignant condition? J Urol 1998;160:1151-1154.

21. McEniff N, Doherty F, Katz J, Schrager CA, Klauber G. Yolk sac tumor of the testis discovered on a routine annual sonogram in a boy with testicular microlithiasis. AJR Am J Roentgenol 1995;164:971-972.

22. Arrigo T, Messina MF, Valenzise M, Rosano M, Alaggio R, Cecchetto G, et al. Testicular microlithiasis heralding mixed germ cell tumor of the testis in a boy. J Endocrinol Invest 2006;29:82-85.

23. Kocaoglu M, Bozlar U, Bulakbas, i N, Saglam M, Uçöz T, Somuncu I. Testicular microlithiasis in pediatric age group: ultrasonography findings and literature review. Diagn Interv Radiol 2005;11:60-65.

24. Bieger RC, Passarge E, McAdams AJ. Testicular intratubular bodies. J Clin Endocrinol Metab 1965;25:1340-1346.

25. Ganem JP, Workman KR, Shaban SF. Testicular microlithiasis is associated with testicular pathology. Urology 1999; 53:209-213.

26. Bennett HF, Middleton WD, Bullock AD, Teefey SA. Testicular microlithiasis: US follow-up. Radiology 2001;218: 359-363.

27. Bach AM, Hann LE, Shi W, Giess CS, Yoo HH, Sheinfeld J, et al. Is there an increased incidence of contralateral testicular cancer in patients with intratesticular microlithiasis? AJR Am J Roentgenol 2003;180:497-500.

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28. Golash A, Parker J, Ennis O, Jenkins BJ. The interval of development of testicular carcinoma in a patient with previously demonstrated testicular microlithiasis. J Urol 2000; 163:239.

29. Salisz JA, Goldman KA. Testicular calcifications and neoplasia in patient treated for subfertility. Urology 1990;36:557560.

30. Frush DP, Kliewer MA, Madden JF. Testicular microlithiasis and subsequent development of metastatic germ cell tumor.

AJR Am J Roentgenol 1996;167:889-890.

31. Howard RG, Roebuck DJ, Metreweli C. The association of mediastinal germ cell tumour and testicular microlithiasis.

Pediatr Radiol 1998;28:998.

32. Quane LK, Kidney DD. Testicular microlithiasis in a patient with a mediastinal germ cell tumour. Clin Radiol 2000;55:642-644.

33. Sato K, Komatsu K, Maeda Y, Ueno S, Koshida K, Namiki M. Case of mediastinal seminoma with testicular microlithiasis. Int J Urol 2002;9:114-116.

34. Nishiyama T, Terunuma M, Iwashima A, Souma T, Hirahara H. Testicular microlithiasis with mediastinal choriocarcinoma: a case report. Int J Urol 1998;5:301-302.

35. Berthelsen JG, Skakkebaek NE. Value of testicular biopsy in diagnosing carcinoma in situ testis. Scand J Urol Nephrol 1981;15:165-168.

36. Von der Maase H, Ro/rth M, Walbom-Jo/ rgensen S, So/rensen BL, Christophersen IS, Hald T, et al. Carcinoma in situ of contralateral testis in patients with testicular germ cell cancer: study of 27 cases in 500 patients. Br Med J (Clin Res Ed) 1986;293:1398-1401.

37. Vachon L, Fareau GE, Wilson MG, Chan LS. Testicular microlithiasis in patients with Down syndrome. J Pediatr 2006;149:233-236.

38. Wasniewska M, Matarazzo P, Weber G, Russo G, Zampolli M, Salzano G, et al. Clinical presentation of McCune-Albright syndrome in males. J Pediatr Endocrinol Metab 2006;19:619-622.

39. Zugor V, Zenker M, Schrott KM, Schott GE. [Frasier syndrome: a rare syndrome with WT1 gene mutation in pediatric urology] [Article in German]. Aktuelle Urol 2006;37: 64-66.

40. Aizenstein RI, Hibbeln JF, Sagireddy B, Wilbur AC, O’Neil HK. Klinefelter’s syndrome associated with testicular microlithiasis and mediastinal germ-cell neoplasm. J Clin Ultrasound 1997;25:508-510.

41. Blau H, Freud E, Mussaffi H, Werner M, Konen O, Rathaus V. Urogenital abnormalities in male children with cystic fibrosis. Arch Dis Child 2002;87:135-138.

42. Bercovitch RS, Januario JA, Terry SF, Boekelheide K, Podis AD, Dupuy DE, et al. Testicular microlithiasis in association with pseudoxanthoma elasticum. Radiology 2005;237: 550-554.

43. Patel RP, Kolon TF, Huff DS, Carr MC, Zderic SA, Canning DA, et al. Testicular microlithiasis and antisperm antibodies following testicular biopsy in boys with cryptorchidism. J Urol 2005;174:2008-2010.

44. Kwan DJ, Kirsch AJ, Chang DT, Goluboff ET, Berdon WE, Hensle DW. Testicular microlithiasis in a child with torsion of the appendix testis. J Urol 1995;153:183-184.

45. Heinemann V, Frey U, Linke J, Dieckmann KP. Testicular microlithiasis -- one case and four points to note. Scand J Urol Nephrol 2003;37:515-518.

46. Kim B, Winter TC 3rd, Ryu JA. Testicular microlithiasis: clinical significance and review of the literature. Eur Radiol 2003;13:2567-2576.

47. Dieckmann KP, Loy V. False-negative biopsies for the diagnosis of testicular intraepithelial neoplasia (TIN) -- an update. Eur Urol 2003;43:516-521.

48. Kliesch S, Thomaidis T, Schutte B, Puhse G, Kater B, Roth S, et al. Update on the diagnostic safety for detection of testicular intraepithelial neoplasia (TIN). APMIS 2003;111:70-74.

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Quiz 1. ª›· ·fi ÙȘ ·Ú·Î¿Ùˆ ÚÔÙ¿ÛÂȘ Ô˘ ·ÊÔÚÔ‡Ó ÙË ÌÈÎÚÔÏÈı›·ÛË ÙˆÓ fiÚ¯ÂˆÓ Â›Ó·È Ï·Óı·Ṳ̂ÓË: ·. √ ÂÈÔÏ·ÛÌfi˜ ηÎÔ‹ıˆÓ ·ı‹ÛÂˆÓ ÙˆÓ fiÚ¯ÂˆÓ Û ·ÛıÂÓ›˜ Ì ÌÈÎÚÔÏÈı›·ÛË fiÚ¯ÂˆÓ Â›Ó·È ÌÈÎÚfiÙÂÚÔ˜ ÛÙ· ·È‰È¿, Û ۯ¤ÛË Ì ÙÔÓ ·ÓÙ›ÛÙÔÈ¯Ô ÙˆÓ ÂÓËϛΈÓ. ‚. √ ÂÈÔÏ·ÛÌfi˜ ηÎÔ‹ıˆÓ ·ı‹ÛÂˆÓ ÙˆÓ fiÚ¯ÂˆÓ Û ·È‰È¿ Ì ÌÈÎÚÔÏÈı›·ÛË fiÚ¯ÂˆÓ Â›Ó·È ÌÈÎÚfiÙÂÚÔ˜ ·fi ÙÔÓ ÂÈÔÏ·ÛÌfi Ù˘ ÌÈÎÚÔÏÈı›·Û˘ ÙˆÓ fiÚ¯ÂˆÓ ÛÂ Ê˘ÛÈÔÏÔÁÈÎfi ÏËı˘ÛÌfi ·È‰ÈÒÓ. Á. °È· ‚Ú·¯˘¯ÚfiÓÈ· ‰È·ÛÙ‹Ì·Ù· ·Ú·ÎÔÏÔ‡ıËÛ˘, Ë Èı·ÓfiÙËÙ· ·Ó¿Ù˘Í˘ ηÎÔ‹ıÂÈ·˜ ÛÙÔ˘˜ fiÚ¯ÂȘ ·ÛıÂÓÒÓ Ì ÌÈÎÚÔÏÈı›·ÛË fiÚ¯ÂˆÓ Â›Ó·È ¯ÚÔÓÔÂÍ·ÚÙÒÌÂÓË Î·È ÂÚ›Ô˘ Ë ›‰È· ÁÈ· ·È‰È¿ Î·È ÂÓ‹ÏÈΘ. ‰. ¢ÂÓ ¤¯ÂÈ ˘ÔÏÔÁÈÛÙ› Ë Èı·ÓfiÙËÙ· ·Ó¿Ù˘Í˘ ηÎÔ‹ıÂÈ·˜ ÙˆÓ fiÚ¯ÂˆÓ Û ·È‰È¿ Ì ̷ÎÚÔ¯ÚfiÓÈ· ÌÈÎÚÔÏÈı›·ÛË fiگˆÓ.

2. ª›· ·fi ÙȘ ·Ú·Î¿Ùˆ ÚÔÙ¿ÛÂȘ Ô˘ ·ÊÔÚÔ‡Ó ÙË ÌÈÎÚÔÏÈı›·ÛË ÙˆÓ fiÚ¯ÂˆÓ Â›Ó·È ÛˆÛÙ‹: ·. ∏ ˘ÂÚ˯ÔÁÚ·ÊÈ΋ ÂÈÎfiÓ· Ù˘ ÌÈÎÚÔÏÈı›·Û˘ ÙˆÓ fiÚ¯ÂˆÓ ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÙËÓ ·ÚÔ˘Û›· ˘ÂÚ˯ÔÁÂÓÒÓ, ÛÙÈÎÙÒÓ ÂÛÙÈÒÓ, ‰È·Ì¤ÙÚÔ˘ ÌÂÁ·Ï‡ÙÂÚ˘ ÙÔ˘ 1 mm, Ì ·ÎÔ˘ÛÙÈ΋ ÛÎÈ¿, ÔÈ Ôԛ˜ ‚Ú›ÛÎÔÓÙ·È ‰È¿Û·ÚÙ˜ ÛÙÔ ÔÚ¯ÈÎfi ·Ú¤Á¯˘Ì·, Û˘Ó‹ıˆ˜ ÌÂ Û˘ÌÌÂÙÚÈÎfi ÙÚfiÔ ÂÌÊ¿ÓÈÛ˘. ‚. ∏ ÌÈÎÚÔÏÈı›·ÛË ÙˆÓ fiÚ¯ÂˆÓ ÔÊ›ÏÂÙ·È Û ÂÓ‰Ô΢ÙÙ¿ÚȘ ÂÓ·Ôı¤ÛÂȘ ·Û‚ÂÛÙ›Ô˘ Î·È fiÙ·Ó Û¯ÂÙ›˙ÂÙ·È Ì fiÁÎÔ˘˜ ÙˆÓ ·Ú¯¤ÁÔÓˆÓ ÁÂÓÓËÙÈÎÒÓ Î˘ÙÙ¿ÚˆÓ (germ cell tumors) ÈÛÙ‡ÂÙ·È fiÙÈ Â›Ó·È ·ÔÙ¤ÏÂÛÌ· ÙÔ˘ ÁÚ‹ÁÔÚÔ˘ ÌÂÙ·‚ÔÏÈÛÌÔ‡ ÙÔ˘ ·Û‚ÂÛÙ›Ô˘ ÛÙ· ·ÙÙ·Ú· ÙÔ˘ fiÁÎÔ˘. Á. √È ÌÈÎÚÔ·Û‚ÂÛÙÒÛÂȘ ÙˆÓ fiÚ¯ÂˆÓ Ô˘ ÔÊ›ÏÔÓÙ·È Û ÂÓ·Ôı¤ÛÂȘ ·Û‚ÂÛÙ›Ô˘ Û ηٿÏÔÈ· ÛÂÚÌ·ÙÈÎÔ‡ ÂÈıËÏ›Ô˘, Ù· ÔÔ›· ΛÙÔÓÙ·È ÂÓÙfi˜ ÙÔ˘ ·˘ÏÔ‡ ÙˆÓ ÛˆÏËÓ·Ú›ˆÓ ‰›ÓÔ˘Ó ıÂÙÈ΋ ÙË ¯ÚÒÛË Ù˘ ·ÈÌ·ÙÔÍ˘Ï›Ó˘. ‰. √È ÌÈÎÚÔ·Û‚ÂÛÙÒÛÂȘ ÌÔÚ› Ó· ÔÊ›ÏÔÓÙ·È Û ÂÓ·fiıÂÛË ·Û‚ÂÛÙ›Ô˘ ÛÙËÓ Â͈ÙÂÚÈ΋ ÂÈÊ¿ÓÂÈ· Û˘ÛÛˆÚÂ˘Ì¤ÓˆÓ Î˘ÙÙ¿ÚˆÓ ÛÂÚÌ·ÙÈÎÔ‡ ÂÈıËÏ›Ô˘ Ô˘ ¤¯Ô˘Ó ˘ÔÛÙ› ÂÎʇÏÈÛË Î·È ÂÈοıÔÓÙ·È Û ÛÙÈ‚¿‰Â˜ ÎÔÏÏ·ÁfiÓÔ˘ Î·È ÁÏ˘ÎÔÚˆÙÂ˚ÓÒÓ.

3. °È· ÙË ‰ÈÂÚ‡ÓËÛË Î·È ·ÓÙÈÌÂÙÒÈÛË ÂÓfi˜ ·È‰ÈÔ‡ Ì ÌÈÎÚÔÏÈı›·ÛË fiÚ¯ÂˆÓ ıˆÚÂ›Ù·È ··Ú·›ÙËÙÔ˜ (Ì›· ÛˆÛÙ‹ ·¿ÓÙËÛË): ·. √ ÌÔÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ ÁÈ· ÙËÓ ·Ó‡ÚÂÛË ÌÂÙ·ÏÏ¿ÍÂˆÓ ÛÙÔ ÁÔÓ›‰ÈÔ SLC34A2 ÙÔ˘ Ù‡Ô˘-IIb Û˘ÌÌÂÙ·ÊÔÚ¤· Na-P Î·È ÙÔ˘ GALNT3 (ÁÈ· ÙËÓ ·Ó›¯Ó¢ÛË ÔÌÔ˙˘ÁˆÙ›·˜ ÁÈ· ÙË “ÛȈËÏ‹” ÌÂÙ¿ÏÏ·ÍË Lys463X). ‚. √ ηڢfiÙ˘Ô˜ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜ ÁÈ· ÙË ‰È¿ÁÓˆÛË ÎÏËÚÔÓÔÌÔ‡ÌÂÓˆÓ Û˘Ó‰ÚfiÌˆÓ (.¯. Û‡Ó‰ÚÔÌÔ Klinefelter, Û‡Ó‰ÚÔÌÔ Down). Á. ŸÏ· Ù· ·Ú·¿Óˆ. ‰. ∫·Ó¤Ó· ·fi Ù· ·Ú·¿Óˆ.

4. °È· ÙËÓ ·Ú·ÎÔÏÔ‡ıËÛË ÂÓfi˜ ·È‰ÈÔ‡ Ì ÌÈÎÚÔÏÈı›·ÛË fiÚ¯ÂˆÓ Û˘ÛÙ‹ÓÔÓÙ·È (Ì›· ÛˆÛÙ‹ ·¿ÓÙËÛË): ·. ∫ÏÈÓÈ΋ ÂͤٷÛË Î·È Â› ÂӉ›ÍˆÓ: ˘ÔÏÔÁÈÛÙÈ΋ ÙÔÌÔÁÚ·Ê›· ‹ Ì·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· (ÂÏ¿ÛÛÔÓÔ˜ ˘¤ÏÔ˘ Î·È ÎÔÈÏ›·˜), ÌÂ Û˘ÓÔ‰fi ÚÔÛ‰ÈÔÚÈÛÌfi ÂÈ¤‰ˆÓ ·-ÂÌ‚Ú˘˚΋˜ ÚˆÙ½Ó˘ Î·È ¯ÔÚÈÔÓÈ΋˜ ÁÔÓ·‰ÔÙÚÔ›Ó˘ ÛÙÔ ·›Ì·. ‚. ∫ÏÈÓÈ΋ ÂͤٷÛË Î·È Â› ÂӉ›ÍˆÓ: ‚ÈÔ„›· fiگˆ˜. Á. ∫ÏÈÓÈ΋ ÂͤٷÛË Î·È ˘ÂÚ˯ÔÁÚ·ÊÈÎfi˜ ¤ÏÂÁ¯Ô˜. ‰. ∫ÏÈÓÈ΋ ÂͤٷÛË Î·È ·Ú·ÎÔÏÔ‡ıËÛË ÙˆÓ ÂÈ¤‰ˆÓ ·-ÂÌ‚Ú˘˚΋˜ ÚˆÙ½Ó˘ Î·È ¯ÔÚÈÔÓÈ΋˜ ÁÔÓ·‰ÔÙÚÔ›Ó˘ ÛÙÔ ·›Ì·. √È ÛˆÛÙ¤˜ ··ÓÙ‹ÛÂȘ ÛÙË ÛÂÏ›‰· 290

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∆È ÚÔηÏ› ÙË ¯ˆÏfiÙËÙ· ÙÔ˘ ∏Ê·›ÛÙÔ˘; ∂. ª·˙ÔÔ‡ÏÔ˘-∫˘Úηӛ‰Ô˘ ¶ÂÚ›ÏË„Ë: O ◊Ê·ÈÛÙÔ˜, Ô √χÌÈÔ˜ ıÂfi˜, Â›Ó·È Ô ı›Ԙ ÌÂÙ·ÏÏÔ˘ÚÁfi˜, ÊËÌÈṲ̂ÓÔ˜ ÁÈ· ÙȘ ÂÊ¢ڤÛÂȘ ÙÔ˘, Ô ÔÔ›Ô˜ ‰›‰·Í ÛÙÔ˘˜ ·ÓıÚÒÔ˘˜ Ï·ÌÚ¤˜ Ù¤¯Ó˜. ∆Ô ÛÙ·ıÂÚfi Â›ıÂÙÔ ÙÔ˘ ∏Ê·›ÛÙÔ˘, Ô˘ ¯ÚËÛÈÌÔÔÈÂ›Ù·È ·fi ÙÔÓ fiÁ‰ÔÔ ·ÈÒÓ· .Ã. ·fi ÙÔÓ ŸÌËÚÔ Î·È ÙÔÓ ∏Û›Ô‰Ô Î·È ¿ÏÏÔ˘˜ ·Ú¯·›Ô˘˜ Û˘ÁÁÚ·Ê›˜ ¤ˆ˜ ÙÔÓ ¤ÌÙÔ ·ÈÒÓ· Ì.Ã., Â›Ó·È “·ÌÊÈÁ˘‹ÂȘ”, ‰ËÏ·‰‹ Ì ·ÌÊfiÙÂÚ· Ù· ÛΤÏË Î˘ÚÙ¿. ∫·Ï›ٷÈ, Â›Û˘, “΢ÏÏÔÔ‰›ˆÓ”, ‰ËÏ·‰‹ Ú·È‚ÔÎÔÈÏÔÔ‰›ˆÓ. ∏ ‰È¿Ï·ÛË ÙÔ˘ ÛÒÌ·Ùfi˜ ÙÔ˘ Î·È ÙÔ Ù˘ÈÎfi ÙÔ˘ ‚¿‰ÈÛÌ· ÂÚÈÁÚ¿ÊÔÓÙ·È ¯·Ú·ÎÙËÚÈÛÙÈο ·fi ÙÔÓ ŸÌËÚÔ Î·È ‚ÔËıÔ‡Ó ÛÙË ‰È¿ÁÓˆÛË. ∏ ·Ó·ËÚ›· ÙÔ˘ ÂÚÈÁÚ¿ÊÂÙ·È ˆ˜ Û˘ÁÁÂÓ‹˜ Î·È Â›Û˘ ·Ó·Ê¤ÚÂÙ·È fiÙÈ Î·È ÔÈ ‰‡Ô ˘ÈÔ› ÙÔ˘ ›¯·Ó ·ÓˆÌ·Ï›Â˜ ÛÙ· fi‰È· ÙÔ˘˜. °È’ ·˘Ù‹ ÙËÓ ·Ó·ËÚ›· ÙÔ˘, ¤¯Ô˘Ó ÚÔÙ·ı› ‰È¿ÊÔÚ˜ ÂÚÌËÓ›˜ Î·È ·ÚÎÂÙ¤˜ Û‡Á¯ÚÔÓ˜ ‰È·ÁÓÒÛÂȘ. ™ÙÔ ¿ÚıÚÔ ·˘Ùfi Á›ÓÂÙ·È Û‡ÓıÂÛË ÛÙÔȯ›ˆÓ ·fi ·Ú¯·›· ÂÏÏËÓÈο ΛÌÂÓ· Î·È ·ÂÈÎÔÓÈÛÙÈΤ˜ Ù¤¯Ó˜ Î·È ÚÔ·ÙÂÈ fiÙÈ Ë ·Ó·ËÚ›· ÙÔ˘ ∏Ê·›ÛÙÔ˘ ‹Ù·Ó Û˘ÁÁÂÓ‹˜ ·ÌÊÔÙÂÚfiÏ¢ÚÔ˜ Ú·È‚Ô˚ÔÔ‰›·.

∆Ô̤·˜ ¶·ıÔÏÔÁ›·˜ Î·È ÃÂÈÚÔ˘ÚÁÈ΋˜ ™ÙfiÌ·ÙÔ˜, √‰ÔÓÙÈ·ÙÚÈ΋ ™¯ÔÏ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ AÏÏËÏÔÁÚ·Ê›·: ∂˘Ù¤ÚË ª·˙ÔÔ‡ÏÔ˘∫˘Úηӛ‰Ô˘ ebazopou@dent.uoa.gr ∆Ô̤·˜ ¶·ıÔÏÔÁ›·˜ Î·È ÃÂÈÚÔ˘ÚÁÈ΋˜ ™ÙfiÌ·ÙÔ˜, √‰ÔÓÙÈ·ÙÚÈ΋ ™¯ÔÏ‹ ¶·ÓÂÈÛÙËÌ›Ô˘ ∞ıËÓÒÓ

§¤ÍÂȘ ÎÏÂȉȿ: ∞Ú¯·›· ÈÛÙÔÚ›· Ù˘ π·ÙÚÈ΋˜, È·ÙÚÈ΋ °ÂÓÂÙÈ΋, ◊Ê·ÈÛÙÔ˜, Û˘ÁÁÂÓ‹˜ ·ÌÊÔÙÂÚfiÏ¢ÚÔ˜ Ú·È‚Ô˚ÔÔ‰›·.

What causes the lameness of Hephaestus? ∂. µazopoulou-∫yrkanidou Abstract: Hephaestus, the Olympian god, was the divine smith, famed for inventions, who taught men glorious crafts. The fixed epithet for Hephaestus, used from the eighth century B.C. by Homer and Hesiod, and other ancient authors up to the fifth century A.D., is “·ÌÊÈÁ˘‹ÂȘ”, i.e. with both feet crooked. He is also called “΢ÏÏÔÔ‰›ˆÓ”, i.e. clubfooted. His body posture and his typical gait are characteristically described by Homer and help in making a diagnosis. His anomaly is described as being congenital, and both his sons are reported as having deformed feet. For this disablement, several interpretations and contemporary medical diagnoses have been proposed. In this article a combination of the information derived from ancient Greek texts and illustrative arts is made and it is concluded that Hephaestus' disability was congenital bilateral talipes equinovarus, i.e. clubfoot.

Pathology and Oral Surgery Sector, Dental School of University of Athens Correspondence: ∂fterpi Bazopoulou∫yrkanidou ebazopou@dent.uoa.gr Pathology and Oral Surgery Sector, Dental School of University of Athens

Key words: Ancient history of medicine, Genetics medical history, Hephaestus, Hephaistos, congenital bilateral clubfoot.

∂ÈÛ·ÁˆÁ‹ ∏ ÂÈÛÙËÌÔÓÈ΋ ÌÂϤÙË ÙˆÓ ·ÓıÚÒÈÓˆÓ ‰˘ÛÌÔÚÊÈÒÓ ¤¯ÂÈ ÂÂÎÙ·ı› Ôχ ηٿ ÙȘ Ë̤Ú˜ Ì·˜. ∂ÓÙÔ‡ÙÔȘ, ÂÌÂÈÚÈΤ˜ ·Ú·ÙËÚ‹ÛÂȘ ‰‡ÛÌÔÚÊˆÓ ·ÙfiÌˆÓ ÌÔÚ› Ó· ·ÓȯÓ¢ıÔ‡Ó ·ÎfiÌ· Î·È Û ·Ú¯·›· ÂÏÏËÓÈο Î·È Ï·ÙÈÓÈο ΛÌÂÓ· (1,2,3,4), ηıÒ˜ Î·È Û ·Ú·ÛÙ¿ÛÂȘ ·fi ÙËÓ ·Ú¯·›· ÎÂÚ·ÌÈ΋ Ù¤¯ÓË, Û ΤÚÌ·Ù·, ·Á¿ÏÌ·Ù· Î·È ¿ÏÏ· ¤ÚÁ· Ù¤¯Ó˘ (5,6,7). °È· ÙÔ Û‡Á¯ÚÔÓÔ ÎÏÈÓÈÎfi, ·ÔÙÂÏ› ÚfiÎÏËÛË Ë ÌÂϤÙË ÙˆÓ ÂÚÈÁÚ·ÊÒÓ ·˘ÙÒÓ, fiˆ˜ Î·È Ë ÚÔÛ¿ıÂÈ· “‰È¿ÁÓˆÛ˘”. ∞˘ÙÔ‡ ÙÔ˘ ›‰Ô˘˜ Ë ÚÔÛ¿ıÂÈ·, ·ÚfiÙÈ ¯ÚÔÓÔ‚fiÚÔ˜, ‰›ÓÂÈ ÙËÓ Â˘Î·ÈÚ›· Ó· ÂÎÙÈÌËıÔ‡Ó ÔÈ Â‡ÛÙԯ˜ ·Ú·ÙËÚ‹ÛÂȘ ·Ú¯·›ˆÓ “ÌË È·ÙÚÈÎÒÓ ÂȉÈÎÒÓ”, ÔÈ Ôԛ˜ Ô‰‹ÁËÛ·Ó ‚·ıÌÈ·›· ÛÙË Û‡Á¯ÚÔÓË È·ÙÚÈ΋ ÁÓÒÛË. ™Ù· ·Ú¯·›· È·ÙÚÈο ΛÌÂÓ·, Ô Ì‡ıÔ˜ Î·È Ë Ú·ÁÌ·ÙÈÎfiÙËÙ· ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È Û˘Ó˘Ê·Ṳ̂ÓÔÈ Ì ÂÚ›ÏÔÎÔ ÙÚfiÔ

Î·È Â›Ó·È ‰‡ÛÎÔÏÔ Ó· ‰È·¯ˆÚÈÛÙÔ‡Ó. ŸÌˆ˜ Ë ÚÔÛ¿ıÂÈ· ·ÔÎ¿Ï˘„˘ Ù˘ ÎÚ˘Ì̤Ó˘ ·Ï‹ıÂÈ·˜ οو ·fi ÙÔÓ Ì‡ıÔ ·ÔÙÂÏ› ÙÔÓ Î·Ï‡ÙÂÚÔ ÙÚfiÔ ÚÔÛ¤ÁÁÈÛ˘ Î·È ÂÎÙ›ÌËÛ˘ Ù˘ ÁÓÒÛ˘ ÙÔ˘ ·ÚÂÏıfiÓÙÔ˜. ™ÙÔ ¿ÚıÚÔ ·˘Ùfi ı· ÂÚÌËÓ¢ÙÔ‡Ó ÛÙÔȯ›· ÁÈ· ÙËÓ ·Ó·ËÚ›· ÙÔ˘ ∏Ê·›ÛÙÔ˘ ·fi ÏÔÁÔÙ¯ÓÈΤ˜ Î·È ·ÂÈÎÔÓÈÛÙÈΤ˜ ηÏÏÈÙ¯ÓÈΤ˜ ËÁ¤˜. ∏ ÂÙ˘ÌÔÏÔÁ›· ÙÔ˘ ÔÓfiÌ·ÙÔ˜ ÙÔ˘ ∏Ê·›ÛÙÔ˘ ·Ú·Ì¤ÓÂÈ ¿ÁÓˆÛÙË, ·ÏÏ¿ Ë Ì·ÚÙ˘Ú›· ÙÔ˘ ·ÓıÚˆÔÓ˘Ì›Ô˘ ∏Ê·›ÛÙÈÔ˜ ÛÙË ÁÚ·Ê‹ °Ú·ÌÌÈ΋ µ ˘Ô‰ËÏÒÓÂÈ fiÙÈ Ô ◊Ê·ÈÛÙÔ˜ ‹Ù·Ó ÁÓˆÛÙfi˜ ÛÙÔ ª˘ÎËÓ·˚Îfi ÎfiÛÌÔ Ù˘ ∂Ô¯‹˜ ÙÔ˘ ÷ÏÎÔ‡. ∂›Ó·È ۯ‰fiÓ ‚¤‚·ÈÔ fiÙÈ Ô ◊Ê·ÈÛÙÔ˜ ‹Ù·Ó ıÂfiÙËÙ· Ù˘ ·Ú¯·›·˜ ¶ÂÏ·ÛÁÈ΋˜ ÂÚÈÔ¯‹˜ ÙÔ˘ ∞ÈÁ·›Ô˘ (8). ™ÙËÓ ∞ı‹Ó· ›¯Â ÂȉÈ΋ ÛÔ˘‰·ÈfiÙËÙ· ÛÙË Ì˘ıÔÏÔÁ›· Î·È ÙË ıÚËÛ΢ÙÈ΋ Ï·ÙÚ›·, ·ÊÔ‡ ÌÂÙ¿ ÙË Û˘Ó¿ÓÙËÛ‹ ÙÔ˘ Ì ÙË ı¿ ∞ıËÓ¿, ¤ÁÈÓ ¶·È‰È·ÙÚÈ΋ 2008;71:283-290

Pediatri Jul-Aug 08

30-07-08

15:53

™ÂÏ›‰·284

284

∂. ª·˙ÔÔ‡ÏÔ˘-∫˘Úηӛ‰Ô˘

·Ù¤Ú·˜ ÙÔ˘ ÚÒÙÔ˘ ‚·ÛÈÏÈ¿ ∂ÚȯıfiÓÈÔ˘ Î·È ˆ˜ ÂÎ ÙÔ‡ÙÔ˘ ÚfiÁÔÓÔ˜ ÙˆÓ ∞ıËÓ·›ˆÓ. ™ÙËÓ ∫Ï·ÛÛÈ΋ ∂Ô¯‹, ¤Ó·˜ ÌÓËÌÂÈ҉˘ Ó·fi˜ ·ÊÈÂÚÒıËΠÛÙÔÓ ◊Ê·ÈÛÙÔ Ì·˙› Ì ÙËÓ ∞ıËÓ¿, ÙÔ 450 Ì.Ã. (9), Ô˘ Û‹ÌÂÚ· Â›Ó·È Û¯Â‰fiÓ Ï‹Úˆ˜ ‰È·ÙËÚË̤ÓÔ˜ ÛÙÔ ÏfiÊÔ ¿Óˆ ·fi ÙËÓ ∞ÁÔÚ¿ ·ÓÙÈÎÚ›˙ÔÓÙ·˜ ÙËÓ ∞ÎÚfiÔÏË. √ ◊Ê·ÈÛÙÔ˜, ıÂfi˜ Ù˘ ʈÙÈ¿˜ Î·È Ù˘ Ù¯ÓÔÏÔÁ›·˜, ·Ú¯Èο Ï·ÙÚ¢fiÙ·Ó ˆ˜ ıÂfi˜ Ù˘ ËÊ·ÈÛÙÂȷ΋˜ Î·È Î·Ù·ÎÏ˘ÛÌÈ΋˜ ʈÙÈ¿˜ ÛÙȘ ËÊ·ÈÛÙÂȷΤ˜ ÂÚÈÔ¯¤˜ Ù˘ ªÂÛÔÁ›Ԣ Î·È Ù˘ ªÈÎÚ¿˜ ∞Û›·˜. ∞ÚÁfiÙÂÚ·, ÙÔÓ ÙÈÌÔ‡Û·Ó ˆ˜ ıÂfi Ù˘ ÂÛÙ›·˜ Î·È ÙÔ˘ ÛȉËÚÔ˘ÚÁ›Ԣ. °ÂÓÓ‹ıËΠÛÙÔÓ ŸÏ˘ÌÔ Ù˘ ª·Î‰ÔÓ›·˜, ÙË Ì˘ıÈ΋ Ô˘Ú¿ÓÈ· ηÙÔÈΛ· ÙˆÓ Ì¤ÁÈÛÙˆÓ ∂ÏÏËÓÈÎÒÓ ıÂÒÓ. °È· ÙË ‚ÈÔÏÔÁÈ΋ Û‡ÏÏË„‹ ÙÔ˘ ˘¿Ú¯Ô˘Ó ‰‡Ô ÂΉԯ¤˜. ™‡Ìʈӷ Ì ÙËÓ ÚÒÙË, Ô˘ ‰fiıËΠ·fi ÙÔÓ ∏Û›Ô‰Ô (20), Ë ◊Ú· ·ÚıÂÓÔÁ¤ÓÓËÛ ÙÔÓ ◊Ê·ÈÛÙÔ. ∞ÏÏ¿ Û‡Ìʈӷ Ì ÙÔÓ ŸÌËÚÔ, Ë ◊Ú· Î·È Ô ∑¢˜ ‹Ù·Ó ÔÈ ÁÔÓ›˜ ÙÔ˘ (22). ∫·È ÔÈ ‰‡Ô ÂΉԯ¤˜ Ù˘ Û‡ÏÏË„‹˜ ÙÔ˘ ·Ó·Ê¤ÚÔÓÙ·È ·fi ÙÔÓ ∞ÔÏÏfi‰ˆÚÔ (23). ¡ˆÚ›˜ ÛÙË ˙ˆ‹ ÙÔ˘, ÂÎÛÊÂÓ‰ÔÓ›ÛÙËΠοو ·fi ÙÔÓ Ô˘Ú·Ófi. √È ı·Ï¿ÛÛȘ ı¤˜, £¤ÙȘ Î·È ∂˘Ú˘ÓfiÌË, ÙÔÓ ‰È¤ÛˆÛ·Ó Î·È ÙÔÓ ÂÚȤı·Ï„·Ó Î·È Ì·˙› ÙÔ˘˜ ¤Ì·ı ٤¯Ó˜ Î·È ¯ÂÈÚÔÙ¯ӛ·. ¶·Ú’ fiÏ· ·˘Ù¿, ÂÎÏ‹ıË ›Ûˆ ÛÙÔÓ ŸÏ˘ÌÔ, fiÔ˘ ¤˙ËÛ ÌÂÙ¤ÂÈÙ· ÛÙÔ ·Ï¿ÙÈ ÙÔ˘, ÂÚÁ·˙fiÌÂÓÔ˜ ÛÙÔ ‰ÈÎfi ÙÔ˘ ÌÂÙ·ÏÏÔ˘ÚÁ›Ô. ∏ ÂȉÂÍÈfiÙËÙ· ÙÔ˘ ∏Ê·›ÛÙÔ˘ ÛÙË ÌÂÙ·ÏÏÔ˘ÚÁ›· Û˘¯Ó¿ ·Ó·Ê¤ÚÂÙ·È ÛÙ· ΛÌÂÓ· ÙÔ˘ √Ì‹ÚÔ˘, ·ÏÏ¿ ηχÙÂÚ· ÂÚÈÏ·Ì‚¿ÓÂÙ·È ÛÙÔ Û¯ÂÙÈÎfi √ÌËÚÈÎfi ⁄ÌÓÔ (10, ÃÃ, 1-7) Î·È ÛÙÔ Î›ÌÂÓÔ (V. 74, 2-4) ÙÔ˘ ¢Èfi‰ˆÚÔ˘ ÙÔ˘ ™ÈÎÂÏÈÒÙË (11). √ ◊Ê·ÈÛÙÔ˜ ›¯Â ·Ó¿ËÚ· fi‰È· Ô˘ ÙÔÓ Î·ıÈÛÙÔ‡Û·Ó ·Ú›۷ÎÙÔ ·Ó¿ÌÂÛ· ÛÙÔ˘˜ Ù¤ÏÂÈÔ˘˜ √χÌÈÔ˘˜ ıÂÔ‡˜. °È’ ·˘Ù‹ ÙËÓ ·Ó·ËÚ›· ÙÔ˘, ¤¯Ô˘Ó ÚÔÙ·ı› Î·È Ú·ÁÌ·ÙÈÛÙÈΤ˜ Î·È Ì˘ıÔÏÔÁÈΤ˜ ÂÚÌËÓ›˜ (9,12,13,4) Î·È ·ÚÎÂÙ¤˜ Û‡Á¯ÚÔÓ˜ ‰È·ÁÓÒÛÂȘ (14,15,16,17). ™ÙÔ ¿ÚıÚÔ ·˘Ùfi, ı· Á›ÓÂÈ ÚÔÛ¿ıÂÈ· Ó· ÂÚÌËÓ¢Ù› Ì ȷÙÚÈÎÔ‡˜ fiÚÔ˘˜ Ë ·Ó·ËÚ›· ·˘ÙÔ‡ ÙÔ˘ ıÂÔ‡ ¯ÚËÛÈÌÔÔÈÒÓÙ·˜ ÙȘ Û¯ÂÙÈΤ˜ ÂӉ›ÍÂȘ ·fi ·Ú¯·›· ÂÏÏËÓÈο ΛÌÂÓ· Î·È ·ÂÈÎÔÓÈÛÙÈΤ˜ Ù¤¯Ó˜.

∂Ӊ›ÍÂȘ ÁÈ· ÙË ¯ˆÏfiÙËÙ· ÙÔ˘ ∏Ê·›ÛÙÔ˘ ∏ ¤Ó‰ÂÈÍË ÁÈ· ÙË ¯ˆÏfiÙËÙ· ÙÔ˘ ∏Ê·›ÛÙÔ˘ ‰È·Ù˘ÒÓÂÙ·È Û ÏÔÁÔÙ¯ÓÈΤ˜ ËÁ¤˜ Ô˘ Î˘Ì·›ÓÔÓÙ·È ·fi ÙÔÓ fiÁ‰ÔÔ ·ÈÒÓ· .Ã. ¤ˆ˜ ÙÔÓ ¤ÌÙÔ ·ÈÒÓ· Ì.Ã. (¶›Ó·Î·˜ 1). ™‡Ìʈӷ Ì ÙÔÓ ∏Úfi‰ÔÙÔ (19), ‹Ù·Ó Ô ŸÌËÚÔ˜, ÙÔÓ fiÁ‰ÔÔ ·ÈÒÓ· .Ã., Ô ÔÔ›Ô˜ ÂÚȤÁÚ·„ ÁÈ· ÚÒÙË ÊÔÚ¿ ÙËÓ Â͈ÙÂÚÈ΋ ÂÌÊ¿ÓÈÛË ÙˆÓ ıÂÒÓ. ∏ Û˘ÁÁÂÓ‹˜ ·ÓˆÌ·Ï›· ÙÔ˘ ∏Ê·›ÛÙÔ˘ O ›‰ÈÔ˜ Ô ◊Ê·ÈÛÙÔ˜ ·Ó·Ê¤ÚÂÈ fiÙÈ Ë ·ÓˆÌ·Ï›· ÙÔ˘ ‹Ù·Ó Û˘ÁÁÂÓ‹˜ (22, iii. 312). ∏ ÌËÙ¤Ú· ÙÔ˘ ◊Ú· ϤÁÂÈ: “·ÏÏ¿ ̘ Û’ fiÏÔ˘˜ ÙÔ˘˜ ıÂÔ‡˜ ·Ó¿ËÚÔ˜ ÁÂÓÓ‹ıËΠPaediatriki 2008;71:283-290

¶›Ó·Î·˜ 1. πÛÙÔÚÈΤ˜ ËÁ¤˜ ηٿ ¯ÚÔÓÔÏÔÁÈ΋ ÛÂÈÚ¿ Ì ÂӉ›ÍÂȘ ÁÈ· ÙË ¯ˆÏfiÙËÙ· ÙÔ˘ ∏Ê·›ÛÙÔ˘ (18) ŸÌËÚÔ˜, ÂÈÎfi˜ ÔÈËÙ‹˜, 8Ô˜ ·ÈÒÓ·˜ .Ã. ∏Û›Ô‰Ô˜, 7Ô˜ ·ÈÒÓ·˜ .à ∏Úfi‰ÔÙÔ˜, ÈÛÙÔÚÈÎfi˜, 5Ô˜ ·ÈÒÓ·˜ .Ã. ∞ÔÏÏÒÓÈÔ˜ Ô ƒfi‰ÈÔ˜, ÂÈÎfi˜ ÔÈËÙ‹˜, 3Ô˜ ·ÈÒÓ·˜ .Ã. ¢Èfi‰ˆÚÔ˜ Ô ™ÈÎÂÏfi˜, ÈÛÙÔÚÈÎfi˜, 1Ô˜-2Ô˜ ·ÈÒÓ·˜ .Ã. ∞ÔÏÏfi‰ˆÚÔ˜, Ì˘ıÔÁÚ¿ÊÔ˜, 1Ô˜-2Ô˜ ·ÈÒÓ·˜ Ì.Ã. ¶·˘Û·Ó›·˜, ÂÚÈËÁËÙ‹˜, 2Ô˜ ·ÈÒÓ·˜ Ì.Ã. ¡fiÓÓÔ˜, ÂÈÎfi˜ ÔÈËÙ‹˜, ‰Â‡ÙÂÚÔ ÌÈÛfi ÙÔ˘ 5Ô˘ ·ÈÒÓ· Ì.Ã.

Ô ˘Èfi˜ ÌÔ˘ Ô ◊Ê·ÈÛÙÔ˜ Ô ÛÙÚ·‚Ôfi‰Ë˜ Ô˘ ÂÁÒ ÙÔÓ ÙÂÎÓÔÔ›ËÛ·” (24, πππ. 316-317). ™ÙȘ √ÌËÚÈΤ˜ ·Ó·ÊÔÚ¤˜, ‰ÂÓ ˘¿Ú¯ÂÈ Û·Ê‹˜ ¤Ó‰ÂÈÍË, Ë ÔÔ›· Ó· ˘Ô‰ËÏÒÓÂÈ fiÙÈ Ù· ÛΤÏË ÙÔ˘ ¤·ı·Ó οٷÁÌ· fiÙ·Ó ÂÎÛÊÂÓ‰ÔÓ›ÛıËΠ·fi ÙÔÓ ŸÏ˘ÌÔ. ∞ÏÏ¿ Ì›· ·Ú¿‰ÔÛË ‰¤Î· ·ÈÒÓˆÓ ·ÚÁfiÙÂÚ· ·˘Ùfi ˘Ô‰ËÏÒÓÂÈ. ∏ πÏÈ¿˜ ‰›‰ÂÈ ‰‡Ô ‰È·ÊÔÚÂÙÈΤ˜ ÂÚÈÁڷʤ˜ Ù˘ ÂΉ›ˆÍ˘ ÙÔ˘ ∏Ê·›ÛÙÔ˘ ·fi ÙÔÓ √˘Ú·Ófi. ™ÙË Ú·„ˆ‰›· ™ Ù˘ πÏÈ¿‰Ô˜, Ë ◊Ú· ÙÔÓ ÂÎÛÊÂÓ‰fiÓÈÛ ·fi ÙÔÓ ŸÏ˘ÌÔ, ÂÂȉ‹ ¤ÓÔȈı ÓÙÚÔÈ·Ṳ̂ÓË ÁÈ· ÙËÓ ·Ú·ÌfiÚʈÛË ÙÔ˘ ˘ÈÔ‡ Ù˘. ∂ÓÒ ÛÙËÓ ÚÒÙË Ú·„ˆ‰›· Ù˘ πÏÈ¿‰Ô˜, Ô ∑¢˜, Î·È fi¯È Ë ◊Ú·, ¤ÚÈÍ ÙÔÓ ◊Ê·ÈÛÙÔ ·fi ÙÔÓ ŸÏ˘ÌÔ (25, ∞.

586-594). ∂›Û˘, ÛÙË µÈ‚ÏÈÔı‹ÎË ÙÔ˘ ∞ÔÏÏfi‰ˆÚÔ˘ (23, I. iii. 5), ·Ó·Ê¤ÚÂÙ·È fiÙÈ Ô ∑¢˜ ÂÎÛÊÂÓ‰fiÓÈÛ ÙÔÓ ◊Ê·ÈÛÙÔ ·fi ÙÔÓ ŸÏ˘ÌÔ Î·È ·˘Ù‹ Ë ÙÒÛË ÚÔοÏÂÛ ÙË ¯ˆÏfiÙËÙ¿ ÙÔ˘. ™ÙË Û˘Ó¤¯ÂÈ· ÂÍÈÛÙÔÚ› fiÙÈ Ô ◊Ê·ÈÛÙÔ˜ ‹Ú ÙËÓ ÂΉ›ÎËÛ‹ ÙÔ˘ ·Áȉ‡ÔÓÙ·˜ ÙË ÌËÙ¤Ú· ÙÔ˘ Û ¤Ó·Ó Âȉ¤ÍÈ· ηٷÛ΢·Ṳ̂ÓÔ ¯Ú˘Ûfi ıÚfiÓÔ Ì ·fiÚ·Ù· ‰ÂÛÌ¿, ·fi ÙÔÓ ÔÔ›Ô ÙÂÏÈÎÒ˜ ·ÂÏ¢ıÂÚÒıËΠÌfiÓÔÓ fiÙ·Ó Ô ¢ÈfiÓ˘ÛÔ˜ ÙÔÓ ¤ÊÂÚ ÌÂı˘Ṳ̂ÓÔ ›Ûˆ ÛÙÔÓ ŸÏ˘ÌÔ. ∏ ÈÛÙÔÚ›· ·˘Ù‹ ‰È·ÌÔÚÊÒıËΠ۠ÏÔÁÔÙ¯ÓÈ΋ ÌÔÚÊ‹ ·fi ÙÔÓ ∞Ïη›Ô (Á‡Úˆ ÛÙ· 600 .Ã.) (26) Î·È Î·Ù·ÁÚ¿ÊËΠ·fi ÙÔÓ ¶·˘Û·Ó›· ÙÔ 2Ô ·ÈÒÓ· Ì.Ã. (27, ∞ÙÙÈ΋. π. xx. 3). ∫·Ù¿ ·˘ÙfiÓ ÙÔÓ ÙÚfiÔ, Ô ◊Ê·ÈÛÙÔ˜, ÂÓÓ¤· ¯ÚfiÓÈ· ÌÂÙ¿ ÙËÓ ÂΉ›ˆÍ‹ ÙÔ˘ ·fi ÙÔÓ ŸÏ˘ÌÔ (25, ™.

395-402), ÂÎÏ‹ıË ›Ûˆ ÛÙË ıÂ˚΋ ηÙÔÈΛ·, fiÔ˘ ¤˙ËÛ ¤ÂÈÙ· ÛÙÔ ·Ï¿ÙÈ ÙÔ˘, ‰Ô˘Ï‡ÔÓÙ·˜ ÛÙÔ ÛȉËÚÔ˘ÚÁÂ›Ô ÙÔ˘.

∆‡Ô˜ Ù˘ ·ÓˆÌ·Ï›·˜ ™‡Ìʈӷ Ì ÙÔÓ Burkert (9), ¤Ó· ¯·Ú·ÎÙËÚÈÛÙÈÎfi ÏÔÁÔÙ¯ÓÈÎÔ‡ ‡ÊÔ˘˜ ÙÔ˘ ŸÌËÚÔ˘ Â›Ó·È Ë ¯Ú‹ÛË ÛÙ·ıÂÚÒÓ ÂÈı¤ÙˆÓ, ÂȉÈο ÁÈ· ıÂÔ‡˜. ∆· Â›ıÂÙ· ·˘Ù¿ ‰È·¯ˆÚ›˙Ô˘Ó ¤Ó· ÛÙÔȯÂÈ҉˜ ¯·Ú·ÎÙËÚÈÛÙÈÎfi ÙÔ˘ ıÂÔ‡, ÙÔ ÔÔ›Ô ·ÔÙ˘ÒÓÂÙ·È ÛÙË ÌÓ‹ÌË Ì ÙË Û˘Ó¯‹ Â·Ó¿ÏË„Ë: “ÓÂÊÂÏËÁÂÚ¤Ù˘ ∑¢˜”, “ÌÂÏ·ÓÔ¯·›Ù˘ ¶ÔÛÂȉÒÓ”. °È· ÙÔÓ ◊Ê·ÈÛÙÔ, ·˘Ùfi ÙÔ ÛÙ·ıÂÚfi Â›ıÂÙÔ Â›Ó·È “·ÌÊÈÁ˘‹ÂȘ”. ∏ ϤÍË ·ÌÊ› Â›Ó·È ÚfiıÂÛË Ô˘ ÛËÌ·›ÓÂÈ ·ÌÊÔÙÂÚÔχڈ˜ Î·È Ë Ï¤ÍË Á˘›ÔÓ ÛËÌ·›ÓÂÈ Ì¤ÏÔ˜. ∂Í¿ÏÏÔ˘, Á‡Ë˜ Â›Ó·È ÙÔ Î˘ÚÙfi ÎÔÌÌ¿ÙÈ

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∂ÈÎfiÓ· 1. £ÂÔÁÔÓ›· - °ÂÓ·ÏÔÁÈÎfi ¢¤Ó‰ÚÔ Ù˘ °·›·˜ (◊Ú· IV-28, ◊Ê·ÈÛÙÔ˜ V-36).

͇ÏÔ˘ ÛÙÔ ¿ÚÔÙÚÔ, ÛÙÔ ÔÔ›Ô ÚÔÛ·ÚÌÔ˙fiÙ·Ó ÙÔ ˘Ó›ÔÓ (29). ™˘ÓÂÒ˜, Ë Ï¤ÍË “·ÌÊÈÁ˘‹ÂȘ” ÛËÌ·›ÓÂÈ Î˘Úو̤ÓÔ˜ Î·È ·fi ÙȘ ‰‡Ô ÌÂÚȤ˜. ∂›Û˘, ÔÈ ÂÚÈÛÛfiÙÂÚÔÈ Û˘ÁÁÚ·Ê›˜ Û˘Ó‰¤Ô˘Ó ÙÔ “·ÌÊÈÁ˘‹ÂȘ” Ì ·Ó·ËÚ›· ÛÙ· fi‰È·. ∂ÈϤÔÓ, Ë ÔÌÔÈfiÙËÙ· ·Ó¿ÌÂÛ· ÛÙÔ Á‡Ë˜, ÙÔ Î˘ÚÙfi ̤ÚÔ˜ ÙÔ˘ ·ÚfiÙÚÔ˘, Î·È ÙËÓ ÎÏÈÓÈ΋ ÌÔÚÊ‹ Ù˘ Ú·È‚Ô˚ÔÔ‰›·˜ Â›Ó·È Î·Ù·Ê·Ó‹˜. ŒÙÛÈ, ηٿ ÙË ÁÓÒÌË ÌÔ˘, Ë ÛËÌ·Û›· Ù˘ Ϥ͈˜ “·ÌÊÈÁ˘‹ÂȘ” ı· Ú¤ÂÈ Ó· ÂÎÏ·Ì‚¿ÓÂÙ·È ˆ˜ ·ÌÊÔÙÂÚfiÏ¢ÚÔ˜ Ú·È‚Ô˚ÔÔ‰›·. √ ◊Ê·ÈÛÙÔ˜ ηÏÂ›Ù·È Î·È “΢ÏÏÔÔ‰›ˆÓ”. ∏ ÛËÌ·Û›· ·˘ÙÔ‡ ÙÔ˘ ÂÈı¤ÙÔ˘ ·Ó·Ê¤ÚÂÙ·È Û·Ê¤ÛÙÂÚ· ÛÙËÓ ·ÓˆÌ·Ï›· ÙˆÓ Ô‰ÈÒÓ ÙÔ˘. ∆Ô Î˘ÏÏfi˜ Â›Ó·È Û˘ÓÒÓ˘ÌÔ ÙÔ˘ Ú·È‚Ô‡, ΢ÚÙÔ‡, Î·È Ô˘˜ Â›Ó·È ÙÔ fi‰È (29). ∂ÈÚÔÛı¤Ùˆ˜, Ô ◊Ê·ÈÛÙÔ˜ ›¯Â “·Ú·È·› ÎÓ‹Ì·È” (·Ú·Èfi˜: ·‰‡Ó·ÙÔ˜, ÏÂÙfi˜) (29). ∂›Û˘, Ô ◊Ê·ÈÛÙÔ˜ ¯·Ú·ÎÙËÚÈ˙fiÙ·Ó fiÙÈ Â›¯Â “ÚÈÎÓÔ‡˜ fi‰·˜”: (·Ú·Èfi˜: ·‰‡Ó·ÙÔ˜, ÏÂÙfi˜) (30). ∂ÎÙfi˜ ·fi ÙÔ ÛÙ·ıÂÚfi Â›ıÂÙÔ “·ÌÊÈÁ˘‹ÂȘ”, ÙÔ ÔÔ›Ô Û·ÊÒ˜ ÔÚ›˙ÂÈ ÙÔÓ ·ÌÊÔÙÂÚfiÏ¢ÚÔ Ù‡Ô Ù˘ ·Ó·ËÚ›·˜ ÙÔ˘, Ë ·ÌÊÔÙÂÚfiÏ¢ÚÔ˜ ·ÓˆÌ·Ï›· ÙÔ˘ Á›ÓÂÙ·È Û·Ê‹˜ Î·È ·fi ÙËÓ ·Ó·ÊÔÚ¿: “ÈÏfi˜ ‰’ ¤ÙÂÚÔÓ fi‰·” (ÂÙÂÚfiÏ¢ÚÔ˜ ¯ˆÏfiÙËÙ·) (25).

∂ÈÎfiÓ· 2. ∫ÔÚÈÓıÈ·Îfi˜ ·ÌÊÔÚ¤·˜, 1Ô Ù¤Ù·ÚÙÔ ÙÔ˘ 6Ô˘ ·È. .Ã. (∂ıÓÈÎfi ∞Ú¯·ÈÔÏÔÁÈÎfi ªÔ˘Û›Ô, ∞ı‹Ó·).

√ ◊Ê·ÈÛÙÔ˜ Î·È Ù· ËÊ·ÈÛÙÔÙ‡ÎÙ· ∞˜ Á˘Ú›ÛÔÌ ÙÒÚ· Û ÈÛÙÔڛ˜ ÁÈ· ÔÚÈṲ̂Ó˜ ı·˘Ì·ÛÙ¤˜ ηٷÛ΢¤˜ ÙÔ˘ ∏Ê·›ÛÙÔ˘ Î·È Ù·˘Ùfi¯ÚÔÓ· ÙË ÛˆÌ·ÙÈ΋ ÙÔ˘ ÂÌÊ¿ÓÈÛË Î·È ÙÔÓ ÙÚfiÔ ‚·‰›ÛÌ·ÙÔ˜, ¶·È‰È·ÙÚÈ΋ 2008;71:283-290

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˙ÂÙ·È ˆ˜ ¤Ó·˜ ÂÏÒÚÈÔ˜ ¿Ó‰Ú·˜, Ì ‰˘Ó·Ùfi ·˘¯¤Ó·, ÙÚȯˆÙ¿ ÛÙ‹ıË, ÔÁÎÒ‰ÂȘ ÒÌÔ˘˜, ·‰‡Ó·Ù˜ ÎӋ̘ Î·È ·ÌÊÔÙÂÚfiÏ¢ÚÔ Ú·È‚Ô˚ÔÔ‰›·.

∂ÈÎfiÓ· 3. ÕÚÔÙÚÔ (§·˚Îfi ªÔ˘ÛÂ›Ô “ÈÚÈfi”, ¢·Ó›ÏÈ·, ∫¤Ú΢ڷ).

·fi ÙËÓ ·Ê‹ÁËÛË ÙÔ˘ √Ì‹ÚÔ˘. ∏ ÚÒÙË ÈÛÙÔÚ›· ·Ó·Ê¤ÚÂÙ·È ÛÙËÓ Â›ÛÎÂ„Ë Ù˘ ÌËÙ¤Ú·˜ ÙÔ˘ ∞¯ÈÏϤ·, £¤Ùȉ·˜, Ô˘ ¤Ú¯ÂÙ·È Ó· ˙ËÙ‹ÛÂÈ ·fi ÙÔÓ ◊Ê·ÈÛÙÔ Ó· ηٷÛ΢¿ÛÂÈ Ù· ηÈÓÔ‡ÚÁÈ· fiÏ· ÙÔ˘ ˘ÈÔ‡ Ù˘: “∂›Â, ÎÈ’ ·fi ÙË ı¤ÛË ÙÔ˘ ·ÌÔÓÈÔ‡ ÛËÎÒıËÎÂ Ô ÂÏÒÚÈÔ˜ fiÁÎÔ˜ ·ÁÎÔÌ·¯ÒÓÙ·˜ Î·È ÎÔ˘ÙÛ·›ÓÔÓÙ·˜Ø Î·È Î¿Ùˆ ÎÈÓÔ‡ÓÙ·Ó ÁÚ‹ÁÔÚ· ÔÈ ·‰‡Ó·Ù˜ ÎӋ̘ ÙÔ˘ Î·È ‚¿‰ÈÛ ÎÔ˘ÙÛ·›ÓÔÓÙ·˜ ÚÔ˜ Ù· ¤Íˆ, ÛÙ· Ï¿ÁÈ· ÙÚ¤¯·Ó ¯Ú˘Û¤˜ ıÂÚ··ÈÓ›‰Â˜ ˘Ô‚·ÛÙ¿˙ÔÓÙ·˜ ÙÔÓ ·Ê¤ÓÙË ÙÔ˘˜ ÎÈ’ ·˘Ùfi˜ Ì ÎfiÔ ÏËÛÈ¿˙ÔÓÙ·˜ ÚÔ˜ ÙÔ Ì¤ÚÔ˜ Ô‡Ù·Ó Ë £¤Ùȉ· ηı›˙ÂÈ ¿Óˆ Û ıÚfiÓÔ Ï·ÌÚfi” (25, ™. 369-423). ∞’ fi,ÙÈ ¤¯ÔÌ ‹‰Ë ÂÈÛËÌ¿ÓÂÈ, ÌÔÚԇ̠ӷ ÂÛÙÈ¿ÛÔÌ ÛÙÔÓ ÙÚfiÔ ‚·‰›ÛÌ·Ùfi˜ ÙÔ˘ ·fi ·˘Ù‹ ÙËÓ ÂÚÈÁÚ·Ê‹. ∞ıÚÔ›˙ÔÓÙ·˜ Ù· ÛÙÔȯ›· ÁÈ· ÙË ÛˆÌ·ÙÈ΋ ηٿÛÙ·ÛË ÙÔ˘ ∏Ê·›ÛÙÔ˘, ¤ÙÛÈ fiˆ˜ ‰›‰ÔÓÙ·È ·fi ÙȘ ÏÔÁÔÙ¯ÓÈΤ˜ ËÁ¤˜, ‚ϤÔÌ fiÙÈ Ô ◊Ê·ÈÛÙÔ˜ ÂÌÊ·Ó›-

∂ÈÎfiÓ· 4. µÚ¤ÊÔ˜ ÌÂ Û˘ÁÁÂÓ‹ ·ÌÊÔÙÂÚfiÏ¢ÚÔ Ú·È‚Ô˚ÔÔ‰›· (¢ÁÂÓÒ˜ ·Ú·¯ˆÚËı›۷ ·fi ÙÔÓ °ÂÒÚÁÈÔ ¶ÈÛÙ‡Ô, Ù¤ˆ˜ ¢È¢ı˘ÓÙ‹ √ÚıÔ·È‰È΋˜ ∫ÏÈÓÈ΋˜, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ ∞ıËÓÒÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”).

Paediatriki 2008;71:283-290

√ ◊Ê·ÈÛÙÔ˜ Û ÂÈÎÔÓÔÁÚ·ÊÈΤ˜ ·ÂÈÎÔÓ›ÛÂȘ ∏ ÂÈηÛÙÈ΋ Ù¤¯ÓË ·ÎÔÏÔ‡ıËÛ ÙËÓ ÂÈ΋ Ô›ËÛË. ŸÔÈ· ›‰ˆÏ· ÎÈ ·Ó ‰È·ÛÒıËÎ·Ó Î·Ù¿ ÙÔ˘˜ “ÛÎÔÙÂÈÓÔ‡˜ ·ÈÒÓ˜” (1200 ¤ˆ˜ 800 .Ã.) Î·È Î·Ù·Û΢¿ÛıËÎ·Ó Î·È ¿ÏÈ ·fi ÙÔÓ 8Ô ·ÈÒÓ· Î·È ÌÂÙ¿, ·˘ÙÔÙÂÏ›˜ ·Ú·ÛÙ¿ÛÂȘ ıÂÒÓ ÂÌÊ·Ó›˙ÔÓÙ·È ÂÚ›Ô˘ ·fi ÙÔ 700. √È ıÂÔ› ‰ÂÓ Â›Ó·È ¿Î·ÌÙ· ·ÓÙÈΛÌÂÓ· Û‚·ÛÌÔ‡, ·ÏÏ¿ ÂÌÊ·Ó›˙ÔÓÙ·È ÛÙËÓ ¤ÓÙ·ÛË Ù˘ Ì˘ıÈ΋˜ ‰Ú¿Ûˆ˜: ·ÚÈÛÙ¿ÓÔÓÙ·È ÂÈÊ¿ÓÂȘ ıÂÒÓ, Ì¿¯Â˜ ıÂÒÓ, ÁÂÓÓ‹ÛÂȘ ıÂÒÓ (9). ŒÙÛÈ, ¤ÚÂ ӷ ‰È·ÌÔÚʈı› ¤Ó·˜ ηÓfiÓ·˜ ÂÈÎÔÓÔÁÚ·ÊÈÎÒÓ ¯·Ú·ÎÙËÚÈÛÙÈÎÒÓ, ÒÛÙ ӷ Â›Ó·È Â‡ÎÔÏÔ Ó· ·Ó·ÁÓˆÚÈÛıÔ‡Ó ÔÈ ıÂÔ›: Ô ∞fiÏÏˆÓ Î·È Ë ÕÚÙÂÌȘ ʤÚÔ˘Ó ÙfiÍÔ, Ô ∞fiÏÏˆÓ ÂÈϤÔÓ ÙË Ï‡Ú·, Ë ◊Ú· ÙÔ Û΋ÙÚÔØ Ë ∞ıËÓ¿ ʤÚÂÙ·È Ï‹Úˆ˜ ÂÍÔÏÈṲ̂ÓË Ì ÂÚÈÎÂÊ·Ï·›·, ·Û›‰·, ·ÎfiÓÙÈÔ Î·È ·ÈÁ›‰·Ø Ô ∂ÚÌ‹˜, Ô ·ÁÁÂÏÈÔÊfiÚÔ˜ ÙˆÓ ıÂÒÓ, ÎÚ·Ù¿ÂÈ ÙÔ ÎËÚ‡ÎÂÈÔ Ì ‰‡Ô ÂÚÈÏÂÁ̤ӷ Ê›‰È· Î·È ÊÔÚ› Ù· ÊÙÂÚˆÙ¿ Û·Ó‰¿ÏÈ·Ø Ô ∑¢˜ ÎÚ·Ù› ÙÔÓ ÎÂÚ·˘Ófi ·ÎfiÌË Î·È ÛÙȘ ÛÂÍÔ˘·ÏÈΤ˜ ÙÔ˘ ‰Ú·ÛÙËÚÈfiÙËÙ˜. √ ◊Ê·ÈÛÙÔ˜ ÎÚ·Ù¿ÂÈ ˘Ú¿ÁÚ· Î·È ÛÊ˘Ú› ‹ ‰ÈÏÔ‡Ó ¤ÏÂ΢ Î·È Î·ÌÈ¿ ÊÔÚ¿ ÊÔÚ¿ÂÈ ›ÏÔÓ ÛÙÔ ÎÂÊ¿ÏÈ ÙÔ˘ (8Ø 27, I, xix. 8). ∏ Ù¤¯ÓË Ù˘ ∫Ï·ÛÛÈ΋˜ ÂÔ¯‹˜ ·Ó¤Ù˘Í ÙËÓ Ù¿ÛË Ó· ηٷÚÁ‹ÛÂÈ fiÛ· Û˘ÓÔ‰Â‡Ô˘Ó ÙÔ˘˜ ıÂÔ‡˜ Î·È Ó· ÙÔ˘˜ ¯·Ú·ÎÙËÚ›ÛÂÈ ÌfiÓÔ ·fi ÙÔ ‘‹ıÔ˜’ ÙÔ˘˜. ™ÙËÓ ÔÌ¿‰· ÙˆÓ ‰Ò‰Âη ıÂÒÓ ÛÙË ÌÂÁ¿ÏË ˙ˆÔÊfiÚÔ ÙÔ˘ ¶·ÚıÂÓÒÓÔ˜, ·ÎfiÌË Î·È Ë ∞ıËÓ¿ ÂÌÊ·Ó›˙ÂÙ·È ¯ˆÚ›˜ ÔÏÈÛÌfiØ Ô ◊Ê·ÈÛÙÔ˜ οıÂÙ·È ‰›Ï· ÛÙËÓ ∞ıËÓ¿. ™ÙÔ Lexicon Iconographicum Mythologiae Classicae (LIMC), 1988 (37), ˘¿Ú¯Ô˘Ó ÂÚÈÛÛfiÙÂÚ˜ ·fi 100 ·ÂÈÎÔÓ›ÛÂȘ ÙÔ˘ ∏Ê·›ÛÙÔ˘ ·fi ·ÁÁÂÈÔÁڷʛ˜, ·Á¿ÏÌ·Ù·, ΤÚÌ·Ù· Î·È ¿ÏÏ· ηÏÏÈÙ¯Ӌ̷ٷ. ∞ÚÎÂÙ¤˜ ¿ÏϘ ‚Ú›ÛÎÔÓÙ·È ‰ÈÂÛ·Ṳ́Ó˜ Û ¿ÏÏ· ¿ÚıÚ· Î·È ‚È‚Ï›·. ∂¤ÏÂÍ· ÔÚÈṲ̂Ó˜ ·fi ·˘Ù¤˜ Ó· ·ÚÔ˘ÛÈ¿Ûˆ Û ¯ÚÔÓÔÏÔÁÈ΋ ÛÂÈÚ¿. √È ÂÚÈÛÛfiÙÂÚ˜ ÚÔ¤Ú¯ÔÓÙ·È ·fi ÙËÓ ∞Ú¯·˚΋ Î·È ÙËÓ ¶ÚÒÈÌË ∫Ï·ÛÛÈ΋ ∂Ô¯‹. ∏ ∞Ú¯·˚΋ Ù¤¯ÓË Â›Ó·È Û·ÊÒ˜ ÚÔ˚fiÓ Ù˘ ÔÈ‹Ûˆ˜ ÙÔ˘ √Ì‹ÚÔ˘ Î·È ÙÔ˘ ∞Ïη›Ô˘. ªÂÚÈΤ˜ ·ÂÈÎÔÓ›˙Ô˘Ó Ì ۷ʋÓÂÈ· ÙË ¯ˆÏfiÙËÙ· ÙÔ˘ ∏Ê·›ÛÙÔ˘, ÂÓÒ ¿ÏϘ ÙËÓ ˘Ô‰ÂÈÎÓ‡Ô˘Ó. ∆ÚÂȘ ·ÁÁÂÈÔÁڷʛ˜ Î·È Ì›· ÂÁ¯¿Ú·ÍË Û ¤Ó· Ûηڷ‚·›Ô ·fi ËÌÈÔχÙÈÌÔ Ï›ıÔ Â›Ó·È ÂÍ·ÈÚÂÙÈο ÛËÌ·ÓÙÈΤ˜, ‰ÈfiÙÈ ·˘Ù¿ Ù· ÙÚ›· ·ÓÙÈΛÌÂÓ· ·ÂÈÎÔÓ›˙Ô˘Ó Û˘ÁÎÂÎÚÈ̤ӈ˜ ÙË ¯ˆÏfiÙËÙ·. ∏ ÚÒÙË ·ÁÁÂÈÔÁÚ·Ê›· ¢ڛÛÎÂÙ·È Û ¤Ó·Ó ∫ÔÚÈÓıÈ·Îfi ·ÌÊÔÚ¤· ÙÔ˘ ÚÒÙÔ˘ ÙÂÙ¿ÚÙÔ˘ ÙÔ˘ 6Ô˘ ·ÈÒÓ· .Ã. (∂ÈÎfiÓ· 2) Î·È ·ÂÈÎÔÓ›˙ÂÈ ÙÔÓ ◊Ê·ÈÛÙÔ Î·Ù¿ ÙËÓ ÂÈÛÙÚÔÊ‹ ÙÔ˘ ÛÙÔÓ ŸÏ˘ÌÔ ˆ˜ ¤Ó· ·ÌÔ‡ÛÙ·ÎÔ ¿ÙÔÌÔ (¤ÊË‚Ô;) Ì ΢ÚÙ¿ fi‰È·, ÂÓÒ ›ÓÂÈ, η‚¿Ï· ·fi

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∂ÈÎfiÓ· 5· Î·È 5‚. §·ÎˆÓÈÎfi˜ ·ÏÈη˜, 6Ô˜ ·ÈÒÓ·˜. .Ã. (∂ıÓÈÎfi ∞Ú¯·ÈÔÏÔÁÈÎfi ªÔ˘ÛÂ›Ô Ù˘ ƒfi‰Ô˘).

ÙË ÌÈ· ÏÂ˘Ú¿ ÂÓfi˜ fiÓÔ˘. √ ·ÌÊÔÚ¤·˜ ·˘Ùfi˜ ¢ڛÛÎÂÙ·È ÛÙÔ ∂ıÓÈÎfi ∞Ú¯·ÈÔÏÔÁÈÎfi ªÔ˘ÛÂ›Ô ÛÙËÓ ∞ı‹Ó·. ª›· ·ÎfiÌË ˘‰Ú›· ·fi ÙÔ 525-520 .Ã. ·ÂÈÎÔÓ›˙ÂÈ ·ÎÚÈ‚¤ÛÙÂÚ· ÙÔÓ ◊Ê·ÈÛÙÔ ˆ˜ Ó·Úfi ·ÁfiÚÈ Ì ÛÙÚ·‚¿ fi‰È·, η‚¿Ï· Û ¤Ó·Ó fiÓÔ Î·Ù¿ ÙËÓ ÂÈÛÙÚÔÊ‹ ÙÔ˘ ÛÙÔÓ ŸÏ˘ÌÔ, ÂÊfiÛÔÓ, Û‡Ìʈӷ Ì ÙËÓ √ÌËÚÈ΋ ·Ú¿‰ÔÛË, ¤ÚÂ ӷ ‹Ù·Ó ÙfiÙ ÂÚ›Ô˘ 9 ÂÙÒÓ. √ ◊Ê·ÈÛÙÔ˜ Ì ·ÌÊfiÙÂÚ· Ù· fi‰È· ΢ÚÙ¿, ·ÏÏ¿ ÁÂÓÂÈÔÊfiÚÔ˜, ·ÂÈÎÔÓ›˙ÂÙ·È, Â›Û˘, Û ¤Ó· §·ÎˆÓÈÎfi ·ÏÈη (∂ÈÎfiÓ· 5), ÙÔ˘ 560 .Ã. ÂÚ›Ô˘, ·fi ÙËÓ π·Ï˘Ûfi, Ô ÔÔ›Ô˜ ¢ڛÛÎÂÙ·È ÛÙÔ ªÔ˘ÛÂ›Ô Ù˘ ƒfi‰Ô˘. √ ∂ÙÚÔ˘ÛÎÈÎfi˜ Ûηڷ‚·›Ô˜ ·fi ËÌÈÔχÙÈÌÔ Ï›ıÔ ¯ÚÔÓÔÏÔÁÂ›Ù·È ·fi ÙÔ 520-510 .Ã. ∂Á¯¿Ú·ÎÙÔ ·ÂÈÎÔÓ›˙ÂÈ ÙÔÓ ◊Ê·ÈÛÙÔ Ì ·ÌÊÔÙÂÚfiÏ¢ÚÔ Ú·È‚Ô˚ÔÔ‰›·, ·Ó¿ÌÂÛ· ÛÙË £¤Ùȉ· Î·È ÙÔÓ ∞¯ÈÏϤ·, Ô ÔÔ›Ô˜ ·Ú·Ï·Ì‚¿ÓÂÈ ÙÔ fiÏ· ÙÔ˘. ™ÙȘ ˘fiÏÔÈ˜ ·ÂÈÎÔÓ›ÛÂȘ Ù˘ ·Ú¯·˚΋˜ Ù¤¯Ó˘, Ô ◊Ê·ÈÛÙÔ˜ ÁÂÓÈÎÒ˜ ·ÚÔ˘ÛÈ¿˙ÂÙ·È ˆ˜ ÌÂÛ‹ÏÈη˜, ÁÂÓÂÈÔÊfiÚÔ˜ ¿Ó‰Ú·˜, η‚¿Ï· Û fiÓÔ Î·Ù¿ ÙËÓ ÂÈÛÙÚÔÊ‹ ÙÔ˘ ÛÙÔÓ ŸÏ˘ÌÔ ‹ ηı‹ÌÂÓÔ˜ Û ÊÙÂÚˆÙfi ¿ÚÌ·, Èı·Ófi˜ ˘·ÈÓÈÁÌfi˜ Ì›·˜ ·fi ÙȘ ı·˘Ì·ÛÙ¤˜ ÂÊ¢ڤÛÂȘ ÙÔ˘ (8), ·ÏÏ¿ Î·È fiÚıÈÔ˜ ÛÙË Á¤ÓÓËÛË Ù˘ ∞ıËÓ¿˜, ÊÔÚÒÓÙ·˜ ÊÙÂÚˆÙ¿ Û·Ó‰¿ÏÈ·, Û·Ó ·˘Ù¿ ÙÔ˘ ∂ÚÌ‹ (Ó· ÙÔÓ ‚ÔËıÔ‡Ó ÛÙÔ ‚¿‰ÈÛÌ·), ‹ Ì ٷ fi‰È· Á˘ÚÈṲ̂ӷ ÚÔ˜ Ù· ¤Ûˆ Î·È ›Ûˆ (37). ∏ ¯ˆÏfiÙËÙ· ÙÔ˘ ∏Ê·›ÛÙÔ˘ ‰ÂÓ ÙÔÓ›˙ÂÙ·È ϤÔÓ Ì ¤ÌÊ·ÛË ¤ÂÈÙ· ·fi ÙÔÓ ¤ÌÙÔ ·ÈÒÓ· (36). ∞fi ·ÁÁÂÈÔÁڷʛ˜ ¯ÚÔÓÔÏÔÁÔ‡ÌÂÓ˜ ·fi ÙÔ 490-480 .Ã. (¶ÚÒÈÌË ∫Ï·ÛÛÈ΋ ∂Ô¯‹), ·ÂÈÎÔÓ›˙ÂÙ·È Î·ıÈṲ̂ÓÔ˜ Û ÛηÌÓ› ÛÙÔ ÂÚÁ·ÛÙ‹ÚÈfi ÙÔ˘, ÊÔÚÒÓÙ·˜ ›ÏÔÓ ÛÙ· ÎÔÓÙ¿ Ì·ÏÏÈ¿ ÙÔ˘ Î·È Â›Ù ‰Ô˘Ï‡ÔÓÙ·˜ Ì·˙› Ì ۷هÚÔ˘˜ (37, 1988: ◊Ê·ÈÛÙÔ˜ 15) ‹ ·Ú·‰›‰ÔÓÙ·˜ Ù· ¿ÚÌ·Ù· ÙÔ˘ ∞¯ÈÏϤ· ÛÙË ÌËÙ¤Ú· ÙÔ˘ £¤Ùȉ· ‹ fiÚıÈÔ˜ Ì ·‰‡Ó·Ù· ÛΤÏË Ì ÙË £¤Ùȉ· ¿ÏÈ. ⁄ÛÙÂÚ· ·fi ÙÔ 470-460 .Ã. (ª¤ÛË ∫Ï·ÛÛÈ΋ ∂Ô¯‹), Ô ◊Ê·ÈÛÙÔ˜ ·ÂÈÎÔÓ›˙ÂÙ·È ˆ˜ ¤Ó·˜ Ù¤ÏÂÈÔ˜ Ê˘ÛÈÔÏÔÁÈÎfi˜ ÁÂÓÂÈÔÊfiÚÔ˜ ¿Ó‰Ú·˜. ¶·ÚÔ˘ÛÈ¿˙ÂÙ·È fiÚıÈÔ˜, Á˘ÌÓfi˜ Ì ÙËÓ

∞ıËÓ¿ Î·È ÙË °·›· ÛÙË Á¤ÓÓËÛË ÙÔ˘ ∂ÚȯıfiÓÈÔ˘ ‹, ηٿ ÙË Á¤ÓÓËÛË Ù˘ ∞ıËÓ¿˜ ·fi ÙËÓ ÎÂÊ·Ï‹ ÙÔ˘ ¢Èfi˜, ÊÔÚ¿ÂÈ ÎÔÓÙfi, ¯ˆÚ›˜ Ì·Ó›ÎÈ· ¯ÈÙÒÓ· Î·È ÎÚ·Ù¿ÂÈ ‰ÈÏÔ‡Ó ¤ÏÂÎ˘Ó ‹ ¿Ïψ˜ Ï·‚›‰· Î·È ÛÊ˘Ú› ηٿ ÙËÓ ÂÈÛÙÚÔÊ‹ ÛÙÔÓ ŸÏ˘ÌÔ. ∫¿Ô˘-οÔ˘ ·Ó¢ڛÛÎÂÙ·È ˆ˜ Ó·Úfi˜, ·Á¤ÓÂÈÔ˜ Ù‡Ô˜, fiˆ˜ Û ¤Ó·Ó ·ÏÈη ÛÙÔ µÚÂÙ·ÓÈÎfi ªÔ˘ÛÂ›Ô ¯ÚÔÓÔÏÔÁÔ‡ÌÂÓÔ ·fi ÙÔ 470-460 .Ã., fiÔ˘ ·ÂÈÎÔÓ›˙ÂÙ·È ˆ˜ Ó·Úfi˜ ¿Ó‰Ú·˜ Ô˘ ‚ÔËı¿ÂÈ ÙËÓ ∞ıËÓ¿ ÛÙË ‰ËÌÈÔ˘ÚÁ›· Ù˘ ¶·Ó‰ÒÚ·˜, ‹ ˆ˜ ¤ÊË‚Ô˜ ÌÂ Ê˘ÛÈÔÏÔÁÈο fi‰È·, η‚¿Ï· Û fiÓÔ Î·Ù¿ ÙËÓ ÂÈÛÙÚÔÊ‹ ÙÔ˘ ÛÙÔÓ ŸÏ˘ÌÔ. ª›· ˙ˆÁÚ·ÊÈ¿ Û ·ÌÊÔÚ¤· Ù˘ ∞Ô˘Ï›·˜ ·ÂÈÎÔÓ›˙ÂÈ ÙÔÓ ◊Ê·ÈÛÙÔ Ì ÙË ÌÔÚÊ‹ ÁÂÓÂÈÔÊfiÚÔ˘ Ó¿ÓÔ˘ Ì ÌÂÁ¿ÏË ÎÔÈÏÈ¿, ÊÔÚÒÓÙ·˜ ¤Ó· ÛÙÂÓfi Ì·ÁÈfi, ¤ÙÔÈÌÔ Ó· Û¿ÛÂÈ Ù· ‰ÂÛÌ¿ Ì ٷ ÔÔ›· ‹Ù·Ó ‰Â̤ÓË Ë ◊Ú·. ÃÚÔÓÔÏÔÁÂ›Ù·È ·fi ÙÔ 330-320 .Ã. (Ù¤ÏÔ˜ ⁄ÛÙÂÚ˘ ∫Ï·ÛÛÈ΋˜ ∂Ô¯‹˜), ¢ڛÛÎÂÙ·È ÛÙË Foggia, ÛÙÔ Museo Civico. ∞˘Ù‹ Ë ÂÈÎfiÓ· ‰ÂÓ Ù·ÈÚÈ¿˙ÂÈ Ì η̛· ¿ÏÏË ÂÈÎÔÓÔÁÚ¿ÊËÛË ÙÔ˘ ıÂÔ‡. ∏ ¯ÚÔÓÔÏÔÁ›· ·˘Ù‹˜ Ù˘ ˙ˆÁÚ·ÊÈ¿˜ ¢ڛÛÎÂÙ·È Ôχ Ì·ÎÚÈ¿ ·fi ÙËÓ ∞Ú¯·˚΋ ∂Ô¯‹, ÔfiÙ·Ó ÏÔÁÔÙ¯ӛ· Î·È Ù¤¯ÓË ‹Û·Ó ·ÎÚȂ›˜ Î·È Ï‹ÚÂȘ Û‚·ÛÌÔ‡ ÚÔ˜ ÙÔ˘˜ ıÂÔ‡˜. ∆· √ÌËÚÈο ŒË Û˘Ó¤¯ÈÛ·Ó Ó· ÂÌÓ¤Ô˘Ó Î·ÏÏÈÙ¤¯Ó˜ Î·È ·ÚÁfiÙÂÚ·, fiˆ˜ ÛÙËÓ ÂÚ›ÙˆÛË ÙÔ˘ John Flaxman (1775-1826) (38). ªÂٷ͇ ÙˆÓ ÁÚ·ÊÈÎÒÓ ¤ÚÁˆÓ ÙÔ˘ ˘¿Ú¯ÂÈ ÌÈ· ·ÂÈÎfiÓÈÛË ÙÔ˘ ∏Ê·›ÛÙÔ˘ Ó· ÂÚ·Ù¿ÂÈ, ˘Ô‚·ÛÙ·˙fiÌÂÓÔ˜ ·fi ÙȘ ·ÌÊÈfiÏÔ˘˜ ηٿ ÙËÓ Â›ÛÎÂ„Ë Ù˘ £¤ÙȉԘ ÛÙÔ ·Ï¿ÙÈ ÙÔ˘ (38). ∞fi ÙËÓ ·Ó·ÛÎfiËÛË ·˘Ù‹ ÙˆÓ Û¯ÂÙÈÎÒÓ ËÁÒÓ Î·ı›ÛÙ·Ù·È Û·Ê¤˜ fiÙÈ ÔÈ ÏÔÁÔÙ¯ÓÈΤ˜ ÂӉ›ÍÂȘ Â›Ó·È ϤÔÓ ·ÍÈfiÈÛÙ˜ ·fi ÙȘ ·ÂÈÎÔÓ›ÛÂȘ ÛÙȘ Ï·ÛÙÈΤ˜ Ù¤¯Ó˜.

™˘˙‹ÙËÛË ∏ ¯ˆÏfiÙËÙ· ÙÔ˘ ∏Ê·›ÛÙÔ˘ ˘‹ÚÍ ·Á·ËÙfi ı¤Ì·, Ú¿ÁÌ·ÙÈ ÌÈ· ‰È·ÁÓˆÛÙÈ΋ ÚfiÎÏËÛË, ÁÈ· ·ÚÎÂÙÔ‡˜ Û˘ÁÁÚ·Ê›˜ ÛÙË Û‡Á¯ÚÔÓË È·ÙÚÈ΋ ÏÔÁÔÙ¯ӛ·. ¶·È‰È·ÙÚÈ΋ 2008;71:283-290

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∂. ª·˙ÔÔ‡ÏÔ˘-∫˘Úηӛ‰Ô˘

∆Ú›· ¿ÚıÚ· (14,16,17), Ì›· ÂÈÛÙÔÏ‹ ÚÔ˜ ÙÔÓ ÂΉfiÙË (15) Î·È ·Ú·ÙËÚ‹ÛÂȘ ‚·ÛÈṲ̂Ó˜ Û ·ÂÈÎÔÓ›ÛÂȘ ·fi ÙÔ˘˜ Silverman, Bartsocas Î·È Schadewaldt, Û˘ÌÂÚÈÏ·Ì‚·ÓfiÌÂÓ˜ ÛÙÔ ‚È‚Ï›Ô ÙˆÓ Kunze Î·È Nippert, 1986 (7), ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÙȘ ·ÎfiÏÔ˘ı˜ ‰È·ÁÓÒÛÂȘ: ·¯ÔÓ‰ÚÔÏ·Û›· (14)Ø ‰È·ÛÙÚÔÊÈ΋ ‰˘ÛÏ·Û›· (15)Ø Ô ◊Ê·ÈÛÙÔ˜ ‹Ù·Ó ÎÔÓÙfi˜, Ó¿ÓÔ˜ (14,16,15)Ø ·ÌÊÔÙÂÚfiÏ¢ÚÔ˜ Ú·È‚Ô˚ÔÔ‰›· (16,17)Ø Â·ÁÁÂÏÌ·ÙÈ΋ ÓfiÛÔ˜ [Vekerdi, 1986, ·Ú·Ù›ıÂÙ·È ˘fi (17)]. ∏ ‰È¿ÁÓˆÛ‹ ÌÔ˘ ›ӷÈ: Û˘ÁÁÂÓ‹˜ ·ÌÊÔÙÂÚfiÏ¢ÚÔ˜ Ú·È‚Ô˚ÔÔ‰›·. ∏ ‰È¿ÁÓˆÛË Ù˘ ·¯ÔÓ‰ÚÔÏ·Û›·˜ ·fi ÙÔÓ Aterman (14) ‚·Û›ÛıËΠ΢ڛˆ˜ Û ‰‡Ô ÛËÌ›·. ¶ÚÒÙÔÓ, ÛÙËÓ ÂÔ›ıËÛË fiÙÈ Ô ◊Ê·ÈÛÙÔ˜ Â›Ó·È Î·Ù’ ¢ı›·Ó ·fiÁÔÓÔ˜ ÙˆÓ ∞ÈÁ˘Ù›ˆÓ ıÂÒÓ Ptah Î·È Bes, ·ÌÊfiÙÂÚÔÈ ·ÂÈÎÔÓÈ˙fiÌÂÓÔÈ ˆ˜ ‰‡ÛÌÔÚÊÔÈ Ó¿ÓÔÈ Ì ΢ÚÙ¿ ÛΤÏË. ∞ÏÏ¿, Â¿Ó ·Ó·‰ÈÊ‹ÛÔÌ ¿ÌÂÛ· ÙȘ ÏÔÁÔÙ¯ÓÈΤ˜ ËÁ¤˜, ¢ڛÛÎÔÌ fiÙÈ Ô ∏Úfi‰ÔÙÔ˜ ÂÚȤÁÚ·„ ¤Ó· ›‰ˆÏÔ ÙÔ˘ ∏Ê·›ÛÙÔ˘ ÛÙËÓ ∞›Á˘ÙÔ, ÙÔ ÔÔ›Ô ‰ÂÓ ‹Ù·Ó ··Ú·Èًو˜ ÙÔ ›‰ÈÔ Ì ÙÔ˘ ÂÏÏËÓÈÎÔ‡ ıÂÔ‡ (19, πππ. 37). √ ºÔ›ÓÈη˜ ¶·Ù¿˚ÎÔ˜ (fiˆ˜ ÙÔÓ ·ÔηÏÔ‡Û·Ó ÔÈ ŒÏÏËÓ˜) ‹Ù·Ó Ô Ptah ‹ Patah Ù˘ ∞ÈÁ‡ÙÔ˘ (¿ÓÙ· Ì ÙË ÌÔÚÊ‹ Ó¿ÓÔ˘), ÙÔÓ ÔÔ›Ô ÔÈ ŒÏÏËÓ˜ Ù·‡ÙÈ˙·Ó Ì ÙÔÓ ◊Ê·ÈÛÙÔ. ¢Â‡ÙÂÚÔÓ, Ô Aterman (14) ˘ÔÛÙËÚ›˙ÂÈ fiÙÈ Ô ◊Ê·ÈÛÙÔ˜ ·Ú¯Èο ÂıˆÚ›ÙÔ Ó¿ÓÔ˜ Î·È ¤Î·Ó ·ÔÙ˘¯Ë̤ÓË ·fiÂÈÚ· Ó· ‚È¿ÛÂÈ ÙËÓ ∞ıËÓ¿ (23) ŸÌˆ˜, ˆ˜ ı· ‹Ù·Ó ‰˘Ó·Ùfi ¤Ó·˜ Ó¿ÓÔ˜ Ó· ÙÔÏÌ‹ÛÂÈ Ó· ‚È¿ÛÂÈ fiÚıÈÔ˜ ÌÈ· Ê˘ÛÈÔÏÔÁÈ΋ Á˘Ó·›Î·; ∂Ú¯fiÌÂÓÔÈ ÛÙË ‰È¿ÁÓˆÛË Ù˘ ‰È·ÛÙÚÔÊÈ΋˜ ‰˘ÛÏ·Û›·˜ ·fi ÙÔÓ Silverman (15), ‚·ÛÈṲ̂ÓË ÛÙȘ ÚÒÈ̘ ·ÁÁÂÈÔÁڷʛ˜ (∂ÈÎfiÓ· 1), ÌÔÚԇ̠¿ÏÈ Ó· Û¯ÔÏÈ¿ÛÔÌ Â› ÙÔ˘ ı¤Ì·ÙÔ˜ Î·È Ó· Â·Ó·Ï¿‚ÔÌ fiÙÈ Ô ◊Ê·ÈÛÙÔ˜ ‰ÂÓ ‹Ù·Ó ÎÔÓÙfi˜. Ÿˆ˜ ‹‰Ë ¤¯ÔÌ ȉ› ÛÙÔ˘˜ ÛÙ›¯Ô˘˜ ÙÔ˘ √Ì‹ÚÔ˘, Ô ◊Ê·ÈÛÙÔ˜ ÂÌÊ·Ó›˙ÂÙ·È ˆ˜ “¤ÏˆÚ ·›ËÙÔÓ”. ÕÏψÛÙÂ, Ò˜ ı· ‹Ù·Ó ‰˘Ó·ÙfiÓ ¤Ó· ¿ÙÔÌÔ Ì ‰È·ÛÙÚÔÊÈ΋ ‰˘ÛÏ·Û›·, Ì ·Ú·ÌÔÚÊÒÛÂȘ ÙˆÓ ¯ÂÈÚÒÓ, fiˆ˜ ·Ó˘„ˆÌ¤ÓÔ ·ÓÙ›¯ÂÈÚ· Î·È Û˘Ó¤ÓˆÛË ÙˆÓ Ê·Ï·ÁÁÒÓ, Î·È ÂÚÈÔÚÈṲ̂ÓË ÎÈÓËÙÈÎfiÙËÙ· Î·È ÂÍ¿ÚıÚˆÛË ÙˆÓ ÌÂÈ˙fiÓˆÓ ·ÚıÚÒÛÂˆÓ (39), ı· ÌÔÚÔ‡Û ÔÙ¤ Ó· ηٷÛ΢¿ÛÂÈ Ù· ı·˘Ì·ÛÙ¿ ÙÔ˘ ∏Ê·›ÛÙÔ˘, fiˆ˜ Ù· ¤¯ÂÈ ÂÚÈÁÚ¿„ÂÈ Ô ŸÌËÚÔ˜ (25, ™. 376 Î·È 416-420). √ ·˘ÙÔÌ·ÙÈÛÌfi˜ ·˘ÙÒÓ ÙˆÓ Î·Ù·Û΢ÒÓ ıˆÚËÙÈο ¤¯ÂÈ ·Ô‰Ôı› ÛÙË Ì·ÁÈ΋ ‰‡Ó·ÌË ÙÔ˘ ∏Ê·›ÛÙÔ˘ Ó· ÂÌÊ˘Û¿ ˙ˆ‹ Û ¿„˘¯· ˘ÏÈο (13). √È ·˘ÙfiÌ·ÙÔÈ ÙÚ›ԉ˜ Î·È ÔÈ ¯Ú˘Û¤˜ ıÂÚ··ÈÓ›‰Â˜ ÂÌÊ·Ó›˙ÔÓÙ·È ˆ˜ Ù· ÚÒÙ· ·Ú·‰Â›ÁÌ·Ù· ·˘ÙÔÌ¿ÙˆÓ, ‰ËÏ·‰‹ ÌÔÚÊÒÓ Ô˘ ÌÈÌÔ‡ÓÙ·È Ú¿ÍÂȘ ˙ˆÓÙ·ÓÒÓ Ï·ÛÌ¿ÙˆÓ (40), Ì ¿ÏÏ· ÏfiÁÈ· robots. ∫·ı›ÛÙ·Ù·È Ê·ÓÂÚfi fiÙÈ “ÂοÛÙË ÁÂÓ¿ ¯ÚÂÈ¿˙ÂÙ·È” fi¯È ÌfiÓÔ “Ì›· Ó¤· ÌÂÙ¿ÊÚ·ÛË ÙÔ˘ √Ì‹ÚÔ˘” (41), ·ÏÏ¿ Î·È Ì›· ηÈÓÔ‡ÚÁÈ· ÂÚÌËÓ›· ÙÔ˘ ıÚ‡ÏÔ˘ οو ·fi ÙË Û‡Á¯ÚÔÓË Ù¯ÓÔÏÔÁÈ΋ ÁÓÒÛË, ·Ó·Áη›· Û˘Ó¤ÂÈ· ÛÙËÓ ·fi‰ÂÈÍË.

Paediatriki 2008;71:283-290

∏ ‰È¿ÁÓˆÛË Ù˘ ·ÌÊÔÙÂÚÔχÚÔ˘ Ú·È‚Ô˚ÔÔ‰›·˜ ·fi ÙÔÓ Bartsocas (16), ·fi ÙÔ˘˜ Bartsocas and Schadewaldt, ÛÙÔ ‚È‚Ï›Ô ÙˆÓ Kunze Î·È Nippert, 1986 (7), Î·È ·fi ÙÔÓ Jobba (17) Â›Ó·È ‚·ÛÈṲ̂ÓË Î˘Ú›ˆ˜ Û ÚÒÈ̘ ·ÁÁÂÈÔÁڷʛ˜ (∂ÈÎfiÓ· 2). ¢ÂÓ ˘¿Ú¯ÂÈ Î·Ì›· ȉȷ›ÙÂÚË ÌÓ›· ÛÙȘ Û¯ÂÙÈΤ˜ ËÁ¤˜ fiÙÈ Ô ◊Ê·ÈÛÙÔ˜ ÁÂÓÓ‹ıËΠÚfiˆÚ·. ∏ ·Ú·ÌfiÚʈۋ ÙÔ˘ ‰ÂÓ ·ÔÙÂÏÔ‡Û ̤ÚÔ˜ Û˘Ó‰ÚfiÌÔ˘. ◊Ù·Ó Û˘ÁÁÂÓ‹˜ Î·È ¤ÙÛÈ ‰ÂÓ ‹Ù·Ó ‰˘Ó·Ùfi Ó· Â›Ó·È Â·ÁÁÂÏÌ·ÙÈ΋ ÓfiÛÔ˜, fiˆ˜ ·Ú¿Ï˘ÛË ÚÔÎÏËı›۷ ·fi ·ÚÛÂÓÈÎfi ¯·ÏÎfi [Vekerdi, 1986, fiˆ˜ ·Ó·Ê¤ÚÂÙ·È ·fi ÙÔÓ Jobba, 1990 (17)]. ∂·ÎfiÏÔ˘ıÔ Ù˘ Û˘˙‹ÙËÛ˘ ·˘Ù‹˜ Â›Ó·È fiÙÈ Ô ◊Ê·ÈÛÙÔ˜ ¯ÒÏ·ÈÓ ÂÂȉ‹ ›¯Â Û˘ÁÁÂÓ‹ ·ÌÊÔÙÂÚfiÏ¢ÚÔ Ú·È‚Ô˚ÔÔ‰›· (∂ÈÎfiÓ· 2). √ Warkany (6) ÂÚÈÁÚ¿ÊÂÈ ·ÛıÂÓ‹ Ì ڷȂÔ˚ÔÔ‰›· (talipes equinovarus), Ë ÔÔ›· Â›Ó·È ·Ú¿ÏÏËÏÔ˜ ÚÔ˜ ÙË ÏÂÙÔÌÂÚ‹ Î·È ÁÂÌ¿ÙË ˙ˆÓÙ¿ÓÈ· ÂÚÈÁÚ·Ê‹ ÙÔ˘ √Ì‹ÚÔ˘. “∏ ·Ú·ÌfiÚʈÛË Â›Ó·È ‰˘Ó·ÙfiÓ Ó· Â›Ó·È ÙfiÛÔ ÛÔ‚·Ú‹ ÒÛÙÂ Ô ·ÛıÂÓ‹˜ Ó· ‚·‰›˙ÂÈ ÛÙËÚÈ˙fiÌÂÓÔ˜ ÛÙÔ Â͈ÙÂÚÈÎfi ¯Â›ÏÔ˜ ÙÔ˘ ¿ÎÚÔ˘ Ô‰fi˜, ÙÔ ÔÔ›Ô ÛÙÚ¤ÊÂÙ·È ·ÎÚÈ‚Ò˜ ÚÔ˜ Ù· ¤Ûˆ, ÚÔ˜ Ù· ¿Óˆ, Î·È Ô›Ûˆ. ∏ Ì˘˚΋ Ì¿˙· ÙÔ˘ Á·ÛÙÚÔÎÓËÌ›Ô˘ Â›Ó·È ÌÂȈ̤ÓË Î·È ÂÓÙÔ›˙ÂÙ·È Ôχ ˘„ËÏ¿, ·ÎÚÈ‚Ò˜ οو ·fi ÙÔ ÁfiÓ·ÙÔ, Ô‡Ùˆ˜ ÒÛÙ ÙÔ Î¿Ùˆ ̤ÚÔ˜ ÙÔ˘ ÛΤÏÔ˘˜ Ó· ÂÌÊ·Ó›˙ÂÙ·È Ôχ ÈÛ¯Ófi (“ÎÓ‹Ì·È ·Ú·È·›”).” ∏ Ú·È‚Ô˚ÔÔ‰›· Â›Ó·È ·fi ÙȘ ÈÔ Û˘¯Ó¤˜ ·Ú·ÌÔÚÊÒÛÂȘ, ÂÌÊ·Ó›˜ ηٿ ÙË Á¤ÓÓËÛË, ηٿ ̤ÛÔ fiÚÔ 1,8/1.000 ÁÂÓÓ‹ÛÂȘ ÛÙȘ ‰È¿ÊÔÚ˜ ¯ÒÚ˜. ∏ Ú·È‚Ô˚ÔÔ‰›· Â›Ó·È ‰˘Ó·Ùfi Ó· ÌÂÙ·‚È‚¿˙ÂÙ·È Û·Ó›ˆ˜ ˆ˜ ·˘ÙÔۈ̷ÙÈÎfi ÂÈÎÚ·Ù¤˜ ¯·Ú·ÎÙËÚÈÛÙÈÎfi, Û‡Ìʈӷ Ì ÔÚÈṲ̂ӷ ÁÂÓ·ÏÔÁÈο ‰¤Ó‰Ú· ηٷÁÚ·Ì̤ӷ ÛÙËÓ È·ÙÚÈ΋ ‚È‚ÏÈÔÁÚ·Ê›· (6,42). ¶·ÚÔ˘ÛÈ¿˙ÂÈ ÂӉȷʤÚÔÓ fiÙÈ Ô ◊Ê·ÈÛÙÔ˜ ›¯Â ‰‡Ô ˘ÈÔ‡˜, ÙÔÓ ¶·Ï·ÈÌfiÓÈÔ Î·È ÙÔ ¶ÂÚÈÊ‹ÙË, Ì ηϋ ۈ̷ÙÈ΋ ‰È¿Ï·ÛË Î·È ·Ó¿ËÚ· fi‰È·, Û‡Ìʈӷ Ì ÙÔÓ ∞ÔÏÏÒÓÈÔ ÙÔÓ ƒfi‰ÈÔ (ÂÈÎfi˜ ÔÈËÙ‹˜, Ô ÔÔ›Ô˜ ÁÂÓÓ‹ıËΠÛÙËÓ ∞ÏÂÍ¿Ó‰ÚÂÈ· ÌÂٷ͇ ÙÔ˘ 295-290 .Ã) Î·È ÙÔÓ ∞ÔÏÏfi‰ˆÚÔ (Ì˘ıÔÁÚ¿ÊÔ˜ ÙÔ˘ 1Ô˘-2Ô˘ ·ÈÒÓ· Ì.Ã.). √ ¶·Ï·ÈÌfiÓÈÔ˜ ‹Ù·Ó ¤Ó·˜ ·fi ÙÔ˘˜ ∞ÚÁÔÓ·‡Ù˜ (23 π. ix.16Ø 36, π. 202-206), fï˜ Ô ¿ÏÏÔ˜ ˘Èfi˜, Ô ¶ÂÚÈÊ‹Ù˘, ‹Ù·Ó ÂÁÎÏËÌ·Ù›·˜ (23, πππ. xvi. 1.) ∞ÏÏ¿ Ô ◊Ê·ÈÛÙÔ˜, ˆ˜ ·ÔÙ¤ÏÂÛÌ· Ù˘ ·ÚÔÛ‰fiÎËÙ˘ Û˘Ó¿ÓÙËÛ‹˜ Ì ÙË ı¿ ∞ıËÓ¿ Î·È Ì ÙË ÌÂÛÔÏ¿‚ËÛË Ù˘ Á˘, Â›Û˘, ¤ÁÈÓ de facto ·Ù¤Ú·˜ ÙÔ˘ ÚÒÙÔ˘ ‚·ÛÈϤˆ˜ ÙˆÓ ∞ıËÓÒÓ, ∂ÚȯıÔÓ›Ô˘. ∏ ·Ó¿ÌÈÍË Ù˘ °·›·˜ ÛÙË Á¤ÓÓËÛË ÙÔ˘ ∂ÚȯıÔÓ›Ô˘ Èı·Ófiٷٷ Û‹Ì·ÈÓ ÙË ‰È·Ù‹ÚËÛË ÙÔ˘ ÈÓ‰¿ÏÌ·ÙÔ˜ Ù˘ ∞ıËÓ¿˜ ˆ˜ ·Úı¤ÓÔ˘ ı¿˜. √ ∞ÔÏÏfi‰ˆÚÔ˜ (23) ÂÚȤÁÚ·„ ÙÔ Ó‹ÈÔ ∂ÚȯıfiÓÈÔ ˆ˜ ¤Ó· Û·ÊÒ˜ ·ÓıÚÒÈÓÔ ‚Ú¤ÊÔ˜ Ì ¤Ó· Ê›‰È ÂÚÈÂÏÈÁ̤ÓÔ Á‡Úˆ ÙÔ˘. √ ∂˘ÚÈ›‰Ë˜ (44) (5Ô˜ ·È. .Ã.) ϤÁÂÈ fiÙÈ Ë ∞ıËÓ¿ ÙÔÔı¤ÙËÛ ‰‡Ô Ê›‰È· ˆ˜

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ÈÏfiÙËÙ· ∏Ê·›ÛÙÔ˘

ʇϷΘ ÙÔ˘ ∂ÚȯıÔÓ›Ô˘ (ÿˆÓ, 20-26). ™ÙËÓ ÂÚ›ÙˆÛË Ô˘ Ô ∂ÚȯıfiÓÈÔ˜ ›¯Â ·Ú·ÌÔÚʈ̤ӷ fi‰È·, Û ۯ‹Ì· Êȉ›ÛÈ·˜ Û›ڷ˜, ı· ‹Ù·Ó ‰˘Ó·Ùfi Ó· ÌÔÈÚ¿˙ÂÙ·È ·˘Ù‹ ÙËÓ ÔÌÔÈfiÙËÙ· Ì ÙÔÓ ·Ù¤Ú· ÙÔ˘ Î·È Ì ÙÔ˘˜ ¿ÏÏÔ˘˜ ‰‡Ô ˘ÈÔ‡˜ ÙÔ˘ ∏Ê·›ÛÙÔ˘, ÂÊfiÛÔÓ fiÏÔÈ ÙÔ˘˜ ›¯·Ó ·Ú·ÌÔÚʈ̤ӷ fi‰È·. ∂ÓÙÔ‡ÙÔȘ, Â›Ó·È ·ÛʷϤÛÙÂÚÔ Ó· Û˘ÌÂÚ¿ÓÔÌ fiÙÈ Ô ∂ÚȯıfiÓÈÔ˜ ›¯Â Ê˘ÛÈÔÏÔÁÈο fi‰È·, Ï·Ì‚¿ÓÔÓÙ·˜ ˘fi„Ë fiÙÈ Ù· Ê›‰È· ‹Ù·Ó ÔÈ Ê‡Ï·Î˜ ÙÔ˘ ‚Ú¤ÊÔ˘˜ Î·È Î·Ù¤ÏËÍ·Ó Ó· Â›Ó·È fi‰È· ÙÔ˘.

∂›ÏÔÁÔ˜ ∞fi ·˘Ù¤˜ ÙȘ ·Ó·Ï‡ÛÂȘ ÙˆÓ ·Ú¯·›ˆÓ ÂÚÈÁÚ·ÊÒÓ ÙÔ˘ ∏Ê·›ÛÙÔ˘ Î·È ÙˆÓ ıˆÚÔ˘Ì¤ÓˆÓ ˘ÈÒÓ ÙÔ˘, ÌÔÚԇ̠ӷ ԇ̠fiÙÈ ˘¿Ú¯ÂÈ ·ÓÙ·Ó¿ÎÏ·ÛË Ù˘ Ú·ÁÌ·ÙÈÎfiÙËÙ·˜ Û ·˘Ù¿ Ù· Ì˘ıÈο ¿ÙÔÌ·. √ ◊Ê·ÈÛÙÔ˜ ·ÓÙÈÚÔÛˆ‡ÂÈ ¤Ó·Ó ÛÎÏËÚ¿ ÂÚÁ·˙fiÌÂÓÔ ¯·ÚÈÛÌ·ÙÈÎfi Ù¯ӛÙË, ÈηÓfi Ó· ηٷÛ΢¿˙ÂÈ ·ÎfiÌ· Î·È ·˘ÙfiÌ·ÙÔ˘˜ Ì˯·ÓÈÛÌÔ‡˜ Ô˘ ı˘Ì›˙Ô˘Ó Û‡Á¯ÚÔÓ· robots. ∏ ۈ̷ÙÈ΋ ÙÔ˘ ηٿÛÙ·ÛË ÂÌÊ·Ó›˙ÂÙ·È ˆ˜ ¤Ó· ·Ú¿‰ÂÈÁÌ· Û˘ÁÁÂÓÔ‡˜ ·ÌÊÔÙÂÚÔχÚÔ˘ Ú·È‚Ô˚ÔÔ‰›·˜. ∞fi ·˘Ù¿ Ù· ÔÏ›Á· ÂÈÙ‡ÁÌ·Ù· Ô˘ ·Ó·Ê¤ÚıËηÓ, ηı›ÛÙ·Ù·È Ê·ÓÂÚfi fiÙÈ Î¿ı ÁÂÓÈ¿ ‰ÂÓ ¯ÚÂÈ¿˙ÂÙ·È ÌfiÓÔ ÌÈ· Ó¤· ÌÂÙ¿ÊÚ·ÛË ÙÔ˘ √Ì‹ÚÔ˘, ·ÏÏ¿ Î·È ÌÈ· ηÈÓÔ‡ÚÁÈ· ÂÚÌËÓ›· ÙÔ˘ ıÚ‡ÏÔ˘ οو ·fi ÙÔ Êˆ˜ Ù˘ Û‡Á¯ÚÔÓ˘ ÂÈÛÙËÌÔÓÈ΋˜ Î·È Ù¯ÓÔÏÔÁÈ΋˜ ÁÓÒÛ˘, ·Ó·Áη›· Û˘Ó¤ÂÈ· Ù˘ ·fi‰ÂÈ͢. ŒÙÛÈ, ¯¿ÚȘ ÛÙËÓ ÂͤÏÈÍË Ù˘ ÂÈÛÙ‹Ì˘ Î·È Ù˘ Ù¯ÓÔÏÔÁ›·˜, ÔÈ Ôԛ˜ ¤ÙÛÈ fiˆ˜ ‰È·ÌÔÚÊÒıËÎ·Ó ‚ÔËıÔ‡Ó ÛÙËÓ Î·Ù·ÓfiËÛË Î·È ÂÚÌËÓ›· ÙˆÓ Ì‡ıˆÓ, ÔÈ ∂ÏÏËÓÈÎÔ› ª‡ıÔÈ “ÁÎÚ¤ÌÈÛ·Ó ÙȘ ‡Ï˜ ÙˆÓ ‚Ô˘‚ÒÓ ·Ó·ÎÙfiÚˆÓ ÙÔ˘˜, ‚ÔÒÓÙ·˜ ÌÈ· ηÈÓÔ‡ÚÁÈ· ·Ï‹ıÂÈ·”, fiˆ˜ ¤ÁÚ·„Â Ô √‰˘ÛÛ¤·˜ ∂χÙ˘ (58). µÈ‚ÏÈÔÁÚ·Ê›· 1. Bartsocas CS. An introduction to ancient Greek genetics and Skeletal Dysplasias. Prog Clin Biol Res 1982;104:3-13.

2. Bartsocas CS. Goiters, dwarfs, giants and hermaphrodites.

In: Papadatos CJ, Bartsocas CS, editors. Endocrine genetics and genetics of growth. New York: Liss; 1985. p. 1-18.

3. Bazopoulou-Kyrkanidou E. Mythos and logos in Hesiod’s Theogony, circa 700 B.C. Am J Med Genet 1996;62: 125-144.

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∫∞£∏ª∂ƒπ¡∏” (The Daily) (Athens), November 3rd 1996.

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™ˆÛÙ¤˜ ··ÓÙ‹ÛÂȘ ÙÔ˘ Quiz ÁÈ· ÙÔ ¿ÚıÚÔ “ªÈÎÚÔÏÈı›·ÛË fiگˆӔ 1. ∏ ·Ú·Î¿Ùˆ ÚfiÙ·ÛË Ô˘ ·ÊÔÚ¿ ÙË ÌÈÎÚÔÏÈı›·ÛË ÙˆÓ fiÚ¯ÂˆÓ Â›Ó·È Ï·Óı·Ṳ̂ÓË: ‚. √ ÂÈÔÏ·ÛÌfi˜ ηÎÔ‹ıˆÓ ·ı‹ÛÂˆÓ ÙˆÓ fiÚ¯ÂˆÓ Û ·È‰È¿ Ì ÌÈÎÚÔÏÈı›·ÛË fiÚ¯ÂˆÓ Â›Ó·È ÌÈÎÚfiÙÂÚÔ˜ ·fi ÙÔÓ ÂÈÔÏ·ÛÌfi Ù˘ ÌÈÎÚÔÏÈı›·Û˘ ÙˆÓ fiÚ¯ÂˆÓ ÛÂ Ê˘ÛÈÔÏÔÁÈÎfi ÏËı˘ÛÌfi ·È‰ÈÒÓ.

2. ∏ ·Ú·Î¿Ùˆ ÚfiÙ·ÛË Ô˘ ·ÊÔÚ¿ ÙË ÌÈÎÚÔÏÈı›·ÛË ÙˆÓ fiÚ¯ÂˆÓ Â›Ó·È ÛˆÛÙ‹: ‰. √È ÌÈÎÚÔ·Û‚ÂÛÙÒÛÂȘ ÌÔÚ› Ó· ÔÊ›ÏÔÓÙ·È Û ÂÓ·fiıÂÛË ·Û‚ÂÛÙ›Ô˘ ÛÙËÓ Â͈ÙÂÚÈ΋ ÂÈÊ¿ÓÂÈ· Û˘ÛÛˆÚÂ˘Ì¤ÓˆÓ Î˘ÙÙ¿ÚˆÓ ÛÂÚÌ·ÙÈÎÔ‡ ÂÈıËÏ›Ô˘ Ô˘ ¤¯Ô˘Ó ˘ÔÛÙ› ÂÎʇÏÈÛË Î·È ÂÈοıÔÓÙ·È Û ÛÙÈ‚¿‰Â˜ ÎÔÏÏ·ÁfiÓÔ˘ Î·È ÁÏ˘ÎÔÚˆÙÂ˚ÓÒÓ.

3. °È· ÙË ‰ÈÂÚ‡ÓËÛË Î·È ·ÓÙÈÌÂÙÒÈÛË ÂÓfi˜ ·È‰ÈÔ‡ Ì ÌÈÎÚÔÏÈı›·ÛË fiÚ¯ÂˆÓ ‰ÂÓ ıˆÚÔ‡ÓÙ·È ··Ú·›ÙËÙÔÈ Ô ÌÔÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ Î·È Ô Î·Ú˘fiÙ˘Ô˜ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜ (ÛˆÛÙ‹ ·¿ÓÙËÛË: ‰).

4. °È· ÙËÓ ·Ú·ÎÔÏÔ‡ıËÛË ÂÓfi˜ ·È‰ÈÔ‡ Ì ÌÈÎÚÔÏÈı›·ÛË fiÚ¯ÂˆÓ Û˘ÛÙ‹ÓÔÓÙ·È: Á. ∫ÏÈÓÈ΋ ÂͤٷÛË Î·È ˘ÂÚ˯ÔÁÚ·ÊÈÎfi˜ ¤ÏÂÁ¯Ô˜.

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ORIGINAL ARTICLE

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Age-related serial plasma citrulline levels in preterm neonates H.P. Ioannou1, E. Diamanti2, Z. Tsampoura2, V. Drossou-Agakidou2, P. Augoustides-Savvopoulou1 Abstract Introduction: Citrulline is a non-essential amino acid that is synthesized almost exclusively in the small intestine. In adults and children with short-bowel syndrome, citrulline has served as a reliable index of the remaining small intestinal length. Citrulline is also a precursor of arginine, the role of which is crucial for neonatal metabolism and growth.

Objective: The aim of this study was to determine serial plasma citrulline levels in stable preterm neonates and to investigate potential changes in relation to time and intestinal maturation.

Methods: Serial plasma citrulline levels were measured in 18 clinically stable preterm neonates with gestational age ≤32 weeks and birth weight ≤1,500 g on days of life 2, 7, 14, 21 and 28. Quantitative analysis of plasma citrulline levels was performed using cation-exchange high performance liquid chromatography with postcolumn derivatization.

Results: In the study population, mean plasma citrulline levels showed a statistically significant progressive increase from 19±4 Ìmol/L on day 2 and 20±4 Ìmol/L on day 7 to 23±4 Ìmol/L on day 14, 29±5 Ìmol/L on day 21, and 31±5 Ìmol/L on day 28 (P<0.01). The route of feeding did not appear to have an affect on plasma levels of citrulline (similar values were obtained from neonates who were fed enterally and parenterally on day 7).

Conclusions: Citrulline levels in normal preterm neonates seem to be age-related and may serve as reference values, facilitating the evaluation of compromised intestinal function in preterm neonates with severe gastrointestinal problems.

1 1st Department of Paediatrics, Metabolic Laboratory, Aristotle University of Thessaloniki, Hippokration General Hospital, Greece 2 1st Department of Neonatology, Aristotle University of Thessaloniki, Hippokration General Hospital, Greece Correspondence: P. Augoustides-Savvopoulou persefon@med.auth.gr 1st Department of Paediatrics, Metabolic Laboratory, Aristotle University of Thessaloniki, Hippokration General Hospital 49 Konstantinoupoleos St., 546 42, Thessaloniki, Greece

Key words: Amino acids, plasma citrulline, preterm neonates, small intestine, parenteral nutrition, enteral feeding tolerance.

Introduction Citrulline is a non-essential amino acid which is not incorporated in proteins and was once considered mainly as a metabolic intermediate in the urea cycle. However, recent studies have underlined the importance of this amino acid in both cellular metabolism and in the monitoring of small intestinal function (1).

Citrulline is synthesized in the liver and the small intestine but only the latter contributes significantly to circulating citrulline levels (2).

Thus citrulline has been proposed as a potential marker of intestinal function. In the last decade, several clinical studies involving patients with short bowel syndrome (3,4) villous atrophy-associated intestinal disease (5) and small intestine transplantation (6,7) have demonstrated that citrulline levels correlate with functional intestinal mass.

Moreover, it has been shown that citrulline is the immediate precursor of arginine, an amino acid with unique properties and with key roles in protein synthesis, ammonia detoxification, creatine and polyamine synthesis and NO produc-

tion (8). In an effort to elucidate the mechanism of arginine deficiency in preterm neonates (9) with the neonatal pig as a model for studying infant nutrition and metabolism, Wu et al. found that both citrulline and arginine production was significantly less in enterocytes of preterm piglets than in term piglets.

Little is known about citrulline concentrations in neonates and published data regarding plasma levels of citrulline in preterms, as far as we are aware, is scarce.

The aim of this study was to determine serial plasma citrulline levels in stable preterm neonates and to investigate potential changes in relation to time and intestinal maturation.

Subjects and methods All neonates participating in the study were admissions to the 1st Neonatal Intensive Care Unit of Hippokration General Hospital. Eighteen preterm neonates of a gestational age ≤32 weeks and birth weight ≤1,500 g with a stable clinical condition, were eligible for the study and were prospectively followed during the study period.

Exclusion criteria included congenital abnormalities, evidence of liver and kidney dysfunction, inborn errors of ¶·È‰È·ÙÚÈ΋ 2008;71:291-295

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Table 1. Patient characteristics No. of patients male:female Birth weight (g) (mean ± SD) Gestational age (wk) SGA IVH (any grade) indomethacin sepsis RDS

Table 2. Amino acid (AA) intakes on the day of blood sampling 18 11:7 1288±165 30.7±1.1 3 (17%) 3 (17%) 0 (0%) 3 (17%) 6 (33%)

*DOL 2 DOL 7 DOL 14 DOL 21 DOL 28 Total AA intake 1.8±0.5 3.6±1.6 3.6±0.3 3.7±0.2 3.6±0.1 (g/kg/day) AA intake via PN 1.6±0.4 2.1±1.3 0.6±1.1 0.3±1 0 (g/kg/day) AA intake via EN 0.2±2 1.6±1.3 3±1.2 3.1±1.2 3.6±0.1 (g/kg/day) DOL=day of life, AA=amino acids, PN=parenteral nutrition, EN=enteral nutrition

SGA=small for gestational age, IVH=intraventricular hemorrhage, RDS=respiratory distress syndrome

metabolism and exchange transfusion during the investigation period.

This study was approved by the ethics committee of the Hospital. Total parenteral nutrition (TPN) was provided according to nursery protocol and all decisions were made independently, by the attending neonatologist. Amino acid supply started on the first postnatal day (Primene 10%). The initial regimen of 1.5 g/kg/d was increased each day by 0.5 g/kg/d until 3 g/kg/d or full enteral feeding with preterm formula (Pre Aptamil - Milupa) was achieved.

EDTA blood samples (up to 500 ÌL) were collected consecutively on days 2, 7, 14, 21 and 28 of life, at the time of sampling for clinically indicated laboratory tests. In order to avoid postprandial amino acid fluctuations in enterally fed neonates, blood samples were drawn immediately before a feeding whereas sampling in the exclusively parenterally fed neonates was random. Blood samples were transported to the laboratory on ice and centrifuged within 30 min at 3000 revs./min for 10 min at 4ÆC. The plasma was deproteinized using sulfosalicylic acid and the deproteinized samples were subsequently

stored at -80ÆC until the day of analysis. Quantitative measurements of plasma amino acids were performed by HPLC (High performance Liquid Chromatography) using a cation exchange column with Li buffers and post column derivitization with ortho-phthalaldehyde.

The results were analyzed by one-way ANOVA for repeated measurements. Differences between the means were determined by linear contrasts. Statistical analysis was performed using SPSS (12.0) for Windows. Probability values <0.05 were taken to indicate statistical significance.

Results Clinical characteristics of the study population are shown in ∆able 1. Amino acid intakes on the days of blood sampling and plasma amino acid levels are presented in Tables 2 and 3, respectively. Daily protein intake of 3 g/kg/day was reached at 4.3±0.7 days of age. Enteral feeds were begun at 2.4±0.8 days and full enteral feeds were established by 11.8±3.9 days. Plasma levels of branched-chain amino acids (valine,

Table 3. Plasma amino acid (AA) concentrations of the studied infants (mean ± SD) DOL 2 Essential AA (Ìmol/L) Histidine 73±22 Isoleucine 51±14 Leucine 88±22 Lysine 170±46 Methionine 35±12 Phenylalanine 73±17 Taurine 107±62 Threonine 135±51 Valine 145±35 Non-Essential AA Alanine 210±75 Asparagine 41±19 Aspartate 11±3 Citrulline 19±4 Glutamine 395±131 Glutamate 33±13 Glycine 238±74 Ornithine 85±26 Serine 124±42 Tyrosine 98±72 Paediatriki 2008;71:291-295

DOL 7

DOL 14

DOL 21

DOL 28

Term infants10

77±20 68±17 111±20 203±60 35±7 60±9 125±43 114±47 185±46

81±19 68±19 121±33 224±68 42±11 63±19 105±33 194±65 168±44

77±31 69±33 118±40 221±73 42±16 63±29 97±41 214±87 152±43

80±16 74±22 133±37 213±61 42±15 60±16 73±33 210±105 150±38

34-119 27-90 53-169 80-232 22-50 22-72

200±73 33±15 13±7 21±5 326±74 45±19 227±85 106±42 131±22 52±31

256±88 54±20 10±5 24±6 412±83 51±17 235±86 118±106 152±29 95±42

284±103 66±28 10±4 29±7 461±146 52±20 222±55 112±80 144±48 105±57

258±73 69±23 10±4 30±7 419±96 80±68 174±49 77±31 123±36 107±43

70-197 88-222 125-647 16-81 14-32 142-851 24-243 77-376 0-157 0-326 38-119

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Plasma citrulline (Ìmol/L)

Citrulline levels in preterm neonates

40 35 30 25 20 15 10 5 0

Table 4. Comparison of amino acid profiles of parenterally and enterally-fed neonates on day of life 7 Amino acid (Ìmol/L)*

2

7

14 Day of life

21

18

Figure 1. Postnatal changes of plasma citrulline levels. Values are presented as means ± SD for 18 neonates.

leucine, isoleucine) increased between days 2 and 7 in parallel with the increase of daily protein intake (1.8±0.5 g/kg/d, 3.7±0.4 g/kg/d, respectively).

Transition to enteral nutrition (day 14) appeared to substantially increase threonine and tyrosine levels.

Plasma amino acid profiles on days 21 and 28 were similar to amino acid profiles of breast-fed term neonates (10). As shown in Table 3, significant differences were observed in plasma amino acid profiles of neonates on total parenteral nutrition and neonates on enteral feeding at the same time point (day 7).

Among these, valine, isoleucine, ornithine and lysine were significantly higher and tyrosine significantly lower in the parenterally fed group (p<0.05). In parenterally fed neonates tyrosine levels were well below reference values (11).

Citrulline levels presented a steady increase in relation to time during the first month of life. Mean plasma concentrations increased from 19 Ìmol/L on day 2 and 20 Ìmol/L on day 7, to 23 Ìmol/L on day 14, 29 Ìmol/L on day 21, and to 34 Ìmol/L on day 28. Comparison of citrulline levels revealed statistically significant differences between days 7 and 14 (p<0.018) and

30 25 20 y=0,5571x + 16,346 R2=0,9846 p<0.001

15 10 5 0 0

5

10

15 Day of life

20

25

30

Figure 2. Correlation of mean plasma citrulline (Ìmol/L) with age of preterm neonates.

EN group

p

229±26 94±19 81±16 137±45 263±51 307±85 74±14 21±3 28±8

145±27 64±18 54±12 85±30 166±31 176±15 61±9 22±4 80±34

p<0.01 p=0.03 p<0.01 p=0.06 p<0.01 p<0.05 p=0.13 p=0.67 p<0.01

* Values are expressed as means ± standard deviation

between days 14 and 21 (p<0.004). In contrast, differences in citrulline values between days 2 and 7 and between days 21 and 28 were not significant. On day 7, neonates on total parenteral nutrition and neonates on enteral feeding showed similar plasma citrulline concentrations (p=0.6). A graphical presentation of plasma citrulline levels in relation to age is shown in Figure 1.

Citrulline levels correlated significantly with the percentage of amino acids administered enterally (R2=0.76, p<0.05). However, regression analysis with plasma citrulline as the response, and percentage of enterally administered amino acids or age as predictors, showed that the influence of age on citrulline levels was the stronger of the two parameters (R2=0.96, P<0.001, Figures 2 and 3).

Discussion The results of this study suggest that plasma citrulline levels in normal preterm neonates increase in relation to age. In addition, a significant linear relationship between the amount of amino acids administered enterally and citrulline levels was found. This

Plasma citrulline (Ìmol/L)

Plasma citrulline (Ìmol/L)

35

Valine Histidine Isoleucine Ornithine Lysine Glycine Phenylalanine Citrulline Tyrosine

PN group

35 30 25 20 15 10 5 0 0,0

y=2,8271x + 15,902 R2=0,7736 p<0.05) 0,5 1,0 1,5 2,0 2,5 3,0 3,5 4,0 Enterally administered amino acids (g/kg/day)

Figure 3. Correlation of mean plasma citrulline levels (Ìmol/L) and amount of amino acids (g/kg/day) administered enterally at time of measurement. ¶·È‰È·ÙÚÈ΋ 2008;71:291-295

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relationship indicates that intestinal maturation, expressed as enteral feeding tolerance, correlates with citrulline values. Interestingly, comparison of citrulline levels between parenterally and enterally fed neonates on day 7 of life, revealed similar values in both groups, suggesting that the route of feeding does not have an effect on plasma citrulline levels.

This was in contrast to the higher concentrations of the majority of plasma amino acids measured on day 7 in parenterally fed neonates, which is to be expected as parenteral nutrition bypasses gut digestion and results in aminoacidemia (Table 4). The pattern of plasma amino acids in neonates maintained on parenteral nutrition reflects the amino acid pattern of the infused mixture, whereas plasma amino acids of enterally fed neonates do not merely reflect the pattern of protein intake but also the extent of metabolism in enteric mucosa and liver (12). It is increasingly being recognized that the small intestine plays a pivotal role in modulating the amino acids delivered to the rest of the body and their circulating levels (13-15). In enteric mucosa amino acids are converted to other amino acids and the latter are released into the bloodstream in order to support ongoing protein synthesis. Another important observation was the substantially reduced plasma tyrosine concentration in neonates on total parenteral nutrition which has been reported by several investigators and is attributed to the poor solubility of tyrosine in parenteral amino acid mixtures (11,1617). As shown in Table 4, progression to enteral feeding normalized tyrosine values.

The gastrointestinal tract (GIT) undergoes marked structural and functional maturation in the periods immediately before and after birth (18). However, a reliable marker of intestinal maturation which would serve as a guide in the feeding or treatment of the immature or compromised gut is lacking. Due to its unique metabolism, citrulline has recently emerged as a promising marker of enterocyte function and as a potential therapeutic supplement for oral, enteral, and parenteral nutrition of gut-compromised patients.

More evidence is needed to support this concept.

Immature infants may have numerous complications including necrotizing enterocolitis. Low plasma arginine concentrations have been described in neonates with necrotizing enterocolitis (NEC).

Zamora et al. (19) reported reduced arginine levels immediately before the onset of NEC, suggesting that the availability of L-arginine may be a factor limiting nitric oxide production, predisposing the immature gut to NEC. Becker et al. (20) observed reduced amino acid levels in premature infants with NEC, especially glutamine and arginine, suggesting that Paediatriki 2008;71:291-295

pathogenesis of NEC may partly be attributed to glutamine and arginine deficiencies.

Recent research has shown that enterocytes (epithelial absorptive cells of the small intestine) are the principal cells responsible for the net synthesis of citrulline and arginine from glutamine and proline in neonates (21,22). This metabolic pathway is crucial for maintaining arginine homeostasis in the neonate.

Wu et al. demonstrated that both citrulline production from glutamine and citrulline conversion into arginine are limited in the enterocytes of preterm piglets as a result of immaturity of key enzymes in the biosynthetic pathway. Impaired intestinal synthesis of citrulline most likely accounts for the reduced availability of citrulline in preterm infants.

Drawing meaningful conclusions about amino acid metabolism based on plasma amino acids is often difficult, as the plasma pool of amino acids is minute in comparison to the free intracellular and proteinbound pools (13). As mentioned above, citrulline is a non-protein amino acid synthesized from glutamine and proline only in the intestine. Recent studies have indicated that citrulline seems to be a reliable index of intestinal function in cases of short bowel syndrome (SBS) both in adults and children (3,4). Citrulline has been shown to have a positive correlation with percent enteral calories in infants with SBS and a cut-off value of ≥19 Ìmol/L had a 94% sensitivity and a 67% specificity for termination of total parenteral nutrition (4).

In conclusion, the present study demonstrates that in preterm neonates there appears to be a progressive increase in plasma citrulline levels in relation to time.

Establishment of reference values is a prerequisite for the evaluation of compromised intestinal function in preterm neonates. It has been shown that conditions or disorders associated with ATP depletion or lactic acidosis, such as sepsis and mucosal ischemia, reduce enterocyte citrulline synthesis in neonatal pigs (23).

Whether plasma citrulline is useful for the evaluation of such conditions in preterm neonates needs further assessment in prospective studies of neonates with normal and compromised intestinal function.

References 1. Curis E, Nicolis I, Moinard C, Osowska S, Zerrouk N, Bénazeth S, et al. Almost all about citrulline in mammals.

Amino Acids 2005;29:177-205.

2. Windmueller HG, Spaeth AE. Source and fate of circulating citrulline. Am J Physiol 1981;241:E473-E480.

3. Crenn P, Coudray-Lucas C, Thuillier F, Cynober L, Messing B. Postabsorptive plasma citrulline concentration is a marker of absorptive enterocyte mass and intestinal failure in humans. Gastroenterology 2000;119:1496-1505.

4. Rhoads JM, Plunkett E, Galanko J, Lichtman S, Taylor L, Maynor A, et al. Serum citrulline levels correlate with enteral

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tolerance and bowel length in infants with short bowel syndrome. J Pediatr 2005;146:542-547.

5. Crenn P, Vahedi K, Lavergne-Slove A, Cynober L, Matuchansky C, Messing B. Plasma citrulline: A marker of enterocyte mass in villous atrophy-associated small bowel disease. Gastroenterology 2003;124:1210-1219.

6. Gondolesi G, Fishbein T, Chehade M, Tschernia A, Magid M, Kaufman S, et al. Serum citrulline is a potential marker for rejection of intestinal allografts. Transplant Proc 2002;34:918-920.

7. Pappas PA, G Tzakis A, Gaynor JJ, Carreno MR, Ruiz P, Huijing F, et al. An analysis of the association between serum citrulline and acute rejection among 26 recipients of intestinal transplant. Am J Transplant 2004;4:1124-1132.

8. Morris SM Jr. Arginine: beyond protein. Am J Clin Nutr 2006;83:508S-512S. 9. Wu G, Jaeger LA, Bazer FW, Rhoads JM. Arginine deficiency in preterm infants: biochemical mechanisms and nutritional implications. J Nutr Biochem 2004;15:442-451.

10. Wu PY, Edwards N, Storm MC. Plasma amino acid pattern in normal term breast-fed infants. J Pediatr 1986;109: 347-349.

11. Roberts SA, Ball RO, Moore AM, Filler RM, Pencharz PB. The effect of graded intake of glycyl-L-tyrosine on phenylalanine and tyrosine metabolism in parenterally fed neonates with an estimation of tyrosine requirement. Pediatr Res 2001;49:111-119.

12. Rassin DK. Amino acids in human milk, formulas and parenteral solutions. In: Cynober LA, editor. Metabolic and therapeutic aspects of amino acids in clinical nutrition.

2nd ed. Boca Raton, FL: CRC Press; 2004. p. 474-478.

13. Wu G. Intestinal mucosal amino acid catabolism. J Nutr 1998;128:1249-1252.

14. Baracos VE. Animal models of amino acid metabolism: a focus on the intestine J Nutr 2004;134:1656S-1659S. 15. Riedijk MA, van Goudoever JB. Splanchnic metabolism of ingested amino acids in neonates. Curr Opin Clin Nutr Metab Care 2007;10:58-62.

16. Heird WC. Amino acids in pediatric and neonatal nutrition. Curr Opin Clin Nutr Metab Care 1998;1:73-78.

17. Brunton JA, Ball RO, Pencharz PB. Current total parenteral nutrition solutions for the neonate are inadequate. Curr Opin Clin Nutr Metab Care 2000;3:299-304.

18. Commare CE, Tappenden KA. Development of the infant intestine: implications for nutrition support. Nutr Clin Pract 2007;22:159-173.

19. Zamora SA, Amin HJ, McMillan DD, Kubes P, Fick GH, Bützner JD, et al. Plasma L-arginine concentrations in premature infants with necrotizing enterocolitis. J Pediatr 1997;131:226-232.

20. Becker RM, Wu G, Galanko JA, Chen W, Maynor AR, Bose CL, et al. Reduced serum amino acid concentrations in infants with necrotizing enterocolitis. J Pediatr 2000;137: 785-793.

21. Wu G, Morris SM Jr. Arginine metabolism: nitric oxide and beyond. Biochem J 1998;336:1-17.

22. Bertolo RF, Brunton JA, Pencharz PB, Ball RO. Arginine, ornithine, and proline interconversion is dependent on small intestinal metabolism in neonatal pigs. Am J Physiol Endocrinol Metab 2003;284:E915-E922.

23. Dillon EL, Knabe DA, Wu G. Lactate inhibits citrulline and arginine synthesis from proline in pig enterocytes. Am J Physiol 1999;276:G1079-G1086.

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Immune status and immune recovery in children with lymphoma at the end of treatment (chemotherapy and/or radiotherapy) and on follow-up evaluation 1 Department of Radiation Oncology 2 Department of Oncology 3 Serology Laboratory 4 Department of Allergy and Immunology, “P. & A. Kyriakou” Children’s Hospital, Athens, Greece Correspondence: Helen Vasilatou-Kosmidis helkosm@yahoo.com Department of Oncology, “P. & A. Kyriakou” Children’s Hospital Thivon and Levadias St., 115 27, Athens, Greece

S. Kosmidis1, A. Pourtsidis2, D. Bouhoutsou2, M. Baka2, M. Varvoutsi2, D. Doganis2, C. Kallergi3, N. Douladiris4, M. Synodinou1, F. Saxoni-Papageorgiou4, H. Vasilatou-Kosmidis2 Abstract Background: Evaluation of the immune status of children with lymphoma after completion of chemotherapy and/or radiotherapy.

Methods: Humoral and cellular immunity were prospectively evaluated in 22 children with lymphoma (11 with Hodgkin's disease and 11 with non-Hodgkin's lymphoma), at the completion of therapy and at 6month intervals for 18 months.

Results: Immunoglobulin (Ig) levels were normal before the onset of therapy in all but one child. At the end of therapy Ig levels had decreased in most children: IgM in 18, IgG in 12, and IgA in 7 children, and 17 of the 22 had decreased CD19 levels. In Hodgkin’s disease, IgG and CD19 levels increased significantly after radiotherapy (P=0.013 and 0.004, respectively). IgM levels remained abnormally low in 16 of 22 children for up to 18 months after treatment completion. At the end of treatment, helper T lymphocyte (CD4) levels were low in 20 children and remained low in 18, and suppressor cell (CD8) levels were elevated in 13 children and remained high in 12 for a period of 6 to 18 months after therapy. Some immunized children became non immune: to polio (15), mumps (6), rubella (5), and measles (1).

Conclusions: In children with lymphoma, IgM levels remained low for long periods after completion of treatment. Helper T lymphocyte levels were low and suppressor cell levels were high at the end of therapy.

Suppressor cells normalized faster, while helper cell levels remained abnormally low for a long period.

Most children became non immune to polio, whereas the majority retained antibodies to ªªR. Despite depressed immunity, serious infections were not documented.

Key words: Lymphoma, immunity, humoral, cellular, recovery.

πntroduction Despite major advances in treating childhood cancer, infections still represent a significant cause of morbidity and mortality, due to immune damage from treatment (1-4). Children with various types of lymphoma may have additional reasons for impaired immunity. Children with Hodgkin’s disease may exhibit abnormalities of the immune system on diagnosis, and in particular enhanced sensitivity of the T suppressor lymphocytes, resulting in impaired cellular immunity (5,6). In addition, polymorphonuclear chemotaxis and metabolic reactivity both decrease during therapy, resulting in enhanced susceptibility to bacterial infection (7). In children with inherited abnormalities of the immune system the incidence of non-Hodgkin’s lymphoma is about 128 times more frequent than in the general population. Lymphomas occur more frequently in patients with WiscottAldrich and ataxia-telengiectasia syndromes, in which both cellular and humoral immunity are Paediatriki 2008;71:296-300

impaired (8,9). After successful treatment for lymphoid malignancies the rate of immune reconstitution varies depending on the type of underlying disease and specific therapy (10,11). In this prospective study, the immune status and the rate of recovery were evaluated in order to determine the role of chemotherapy and/or radiotherapy in children with lymphomas.

Patients and Methods The protocol of this study, including informed consent, was approved by the Ethical Committee of the “P. & A. Kyriakou” Children’s Hospital of Athens. Twenty two children with lymphomas were enrolled and studied at the end of their outlined therapy scheme and at 6, 12 and 18 months after completion of treatment. In addition, the children with Hodgkin’s disease were evaluated before and after radiotherapy. For the evaluation of humoral immunity, serum levels of IgG, IgA and IgM were studied by nephelometry and expressed in mg/dl, and CD19 levels were studied by flow cytometry. In addition qualitative and quantitative response to previous immunization for polio and MMR was studied: Values of <5 IU/ml for rubella and titers of <1/20 for polio were

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Hodgkin’s disease

non-Hodgkin’s lymphoma

N Median age (years) Histology

11 11 12.5 10.5 NS* 10 lymphoblastic 3 (2 years)*** MC** 1 undifferentiated 7 (4-6 months)*** large cell 1 (2 years)*** Stage I 1 II 7 III 2 IV 1 B-symptoms 8/11 Site above diaphragm 8 6 below diaphragm 3 3 bones/CNS 2 *

NS: nodular sclerosis MC: mixed cellularity *** duration of treatment **

considered as loss of immunity. Evaluation of cellular immunity included enumeration of the lymphocyte subpopulation (CD3, CD4, CD8, CD16, CD3HLADR, CD45RO and CD45RA) by flow cytometry using a FACScan instrument (Becton-Dickinson, Mountain View, CA). The results were expressed as median values of the percent of total lymphocyte count and were analyzed using the non-parametric Mann-Whitney U test.

Of the 22 children, 11 had Hodgkin’s disease and 11 had non-Hodgkin’s lymphoma. The characteristics of the patients are shown in Table 1. Children with Hodgkin’s disease were treated according to the SFOP HD 90/93 protocol, which included 4-6 courses of chemotherapy the type of which depended on the stage of disease, followed by radiotherapy 20Gy to the primary disease site, plus to the spleen in 8/11 patients in whom B general symptoms were present (12). Children with nonHodgkin’s lymphoma were treated with chemotherapy alone according to the histology and immunophenotyping, and the duration of treatment ranged from 4 to 24 months (13).

1200 1000 mg/dl

Table 1. Patient characteristics of children with lymphomas

800

Before RT After RT 6 months 12 months 18 months

600 400 200 0

IgG

IgA

IgM

Figure 1. Median immunoglobulin levels of patients with Hodgkin's disease at various time-points. RT: radiotherapy.

Results All children but one had normal immunoglobulin levels prior to therapy. In both groups at the end of chemotherapy the humoral immunity was depressed in most children: IgG was decreased in 13, IgA in 8, IgM in 19 and CD19 in 17 of 22 children. Also, 15 children had completely lost their immunity to polio, 6 to mumps, 5 to rubella and one to measles, and these findings did not change throughout the observation period. Evaluation of cellular immunity showed increased T suppressor cells CD8 in 15, decreased helper cells CD4 in 15 and increased natural killer cells CD16 in 18 of 22 children. In children with Hodgkin’s disease, evaluation before and after radiotherapy showed significant increase of IgG (p=0.013) and of CD19 (p=0.004). Other changes in cellular immunity were also documented (increased suppressors in 6, decreased helpers in 10 and increased natural killers in 7 children) although statistically these were non significant.

Statistically significant changes of cellular immunity persisted at 6, 12 and 18 months after completion of treatment, and specifically: a) end of treatment versus 6 months later, decrease in memory cells CD45RO

50 Normal CD4 (median)

45

%

40 35

CD4

30

Normal CD8 (median)

25 20

CD8

15 10 5 0 Before RT

After RT

6 months

12 months

18 months

Figure 2. Median CD4 and CD8 values of patients with Hodgkin’s disease at various time-points. RT: radiotherapy. ¶·È‰È·ÙÚÈ΋ 2008;71:296-300

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IgM 350 300

mg/dl

250

Upper normal

200

Lower normal

150

NHL HD

100 50 0 End therapy

6 months

12 months

18 months

Figure 3. Median IgM values at various time-points. NHL: non-Hodgkin’s lymphoma, HD: Hodgkin’s disease.

(p=0.020) and increase in naïve cells CD45RA (p=0.002); b) end of treatment versus 18 months later, increase in activated cells CD3DR (p=0.048), decrease in memory cells CD45RO (p=0.011) and increase in naïve cells CD45RA (p=0.031). In Figures 1 and 2 median immunoglobulin and helper and suppressor cell levels in the study population are shown, compared to normal median values. In children with nonHodgkin’s lymphoma, comparison of values at the end of therapy and 6 months later showed significant decrease in natural killer cells CD16 (p=0.007) and memory cells CD45RO (p=0.003) and significant increase in naïve cells CD45RA (p=0.005). Comparison of values at the end of treatment and 12 months later showed significant increase in IgG (p=0.015) and IgM (p=0.011), although the latter was still very low, and significant decrease in activated CD3DR cells (p=0.02) and memory cells CD45RO (p=0.006). In both groups of patients IgM levels remained low and CD16 levels

kept decreasing, but with a slight increase in Hodgkin’s disease towards 18 months after completion of treatment (Figures 3 and 4). Memory and naïve cells followed the same curve in Hodgkin’s disease and nonHodgkin’s lymphoma, with gradually decreasing CD45RO and gradually increasing CD45RA (Figure 5).

Two children with Hodgkin’s disease developed Herpes zoster infection within the radiation field, but serious infections in children with non-Hodgkin’s lymphoma were documented only during neutropenia.

Discussion Lymphomas in children are currently treated effectively with chemotherapy, and Hodgkin’s disease with a combination of chemotherapy and radiotherapy. It has been shown that after completion of treatment patients continue to be immunosuppressed for variable periods of time (14,15). Most studies refer to children with leukaemia, in whom severe and long

CD16 level 25 20 Upper normal Lower normal

%

15

HD 10

NHL

5 0 End therapy

6 months

12 months

18 months

Figure 4. Median CD16 values at various time-points. NHL: non-Hodgkin’s lymphoma, HD: Hodgkin’s disease.

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80 70 CD45RO HD

60 %

CD45RO NHL 50

CD45RA HD CD45RA NHL

40 30 20 End therapy

6 months

12 months

18 months

Figure 5. Median CD45RO and CD45RA values at various time-points. NHL: non-Hodgkin’s lymphoma, HD: Hodgkin’s disease.

lasting damage of the immune system has been shown (10,14,16). In a large study evaluating children with various malignancies it was shown that at the time of diagnosis patients with Hodgkin’s disease had the highest IgG and IgA levels and those with nonHodgkin’s lymphoma had the highest IgM levels. IgG levels declined after chemotherapy in Hodgkin’s disease, and this drop lasted longer than that observed in leukaemia. Also IgM was observed to be profoundly decreased in non-Hodgkin’s lymphoma and to remain low for a long period of time (17). All but one of the patients in the present study had normal immunoglobulin levels at the time of diagnosis, but all 3 subclasses showed a decrease after chemotherapy in the majority of patients. IgM levels remained low for as long as 18 months after treatment completion. In previous studies, at the time of discontinuation of therapy in children with Hodgkin’s disease 38% of patients had low IgG and 89% had low IgM levels which gradually recovered (11). In contrast, in the present study, although similarly low at therapy completion, IgM levels both in Hodgkin’s disease and non-Hodgkin’s lymphoma, remained low. The significant increase of both IgG and CD19 levels after radiotherapy probably reflects humoral recovery after chemotherapy completion rather than a positive effect of radiotherapy, although the number of children studied is small. It has also been reported that levels of natural killer cells (CD16), CD4 and CD8 were abnormal at therapy completion in the majority of Hodgkin’s disease patients and subsequently improved over time (11). This study, as others, shows that suppressor CD8 cells recovered faster than helper CD4 cells, and this may reflect CD8 regeneration via an independent thymic pathway (10,18,19).

Previous studies have shown that radiation in dosages of up to 20Gy increases the activity of natural killer cells and that their activity is normal in patients with lymphoma after therapeutic cervical irradiation, whereas other studies suggest that the increase natural killer activity in irradiated leukaemia patients may be attributed to humoral factors (1921). The present study shows that in both Hodgkin’s disease and non-Hodgkin’s lymphoma natural killer cells start at high levels at the end of therapy and gradually decrease by 6 and 12 months post-treatment, after which they either keep on dropping (nonHodgkin’s lymphoma) or start increasing (Hodgkin’s disease) at 18 months. Literature reports suggest that most children with leukaemia lose memory to prior immunization (22) in contrast to the experience of this group published earlier (10). Children with Hodgkin’s disease may lose their immunity to pertussis and tetanus from prior immunization, and less frequently to polio (11). In this study, 68% of immunized patients had lost their immunity to polio by the end of therapy. The absence of antibodies to polio persisted 18 months after completion of treatment.

This group has previously shown that in children with leukaemia CD45RO memory cells continue to decline significantly for up to 18 months post therapy (10). In the present study in both Hodgkin’s disease and non-Hodgkin’s lymphoma, CD45RO memory cells gradually dropped, reaching very low levels 18 months after therapy completion while over the same period the naïve CD45RA cells were gradually increasing. Various factors such as age, sex, duration of therapy could not be evaluated separately due to the small number of our group of patients.

In conclusion, in children with lymphoma, the ¶·È‰È·ÙÚÈ΋ 2008;71:296-300

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immunoglobulin levels had decreased at the end of therapy and IgM levels remained low for a prolonged period of time. Helper T lymphocyte levels were low and suppressor cell levels were high at the end of therapy. Suppressor cells normalized faster, whereas helper cell levels remained abnormally low for a long period of time. The improvement of humoral immunity following radiotherapy for Hodgkin’s disease could be attributed to recovery from the earlier chemotherapy. Both CD16 natural killers and CD45RO memory cells decreased following completion of treatment. Most of the children became non immune to polio, whereas the majority retained antibodies to ªªR. Despite their depressed immunity, and even though the spleen was irradiated in the majority of children with Hodgkin’s disease, serious infections attributable to impaired immunity were not documented.

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9. Seibel N, Cossman J, Magrath IT. Lymphoproliferative Disorders. In: Pizzo PA, Poplack DG, editors. Principles and Practice of Pediatric Oncology. 3rd ed. Philadelphia: Lippincott; 1997. p. 589-615.

10. Kosmidis S, Baka M, Bouhoutsou D, Doganis D, Kallergi C, Douladiris N, et al. Longitudinal assessment of im-

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13. Patte C, Auperin A, Gerrard M, Michon J, Pinkerton R, Sposto R, et al. Results of the randomized international FAB/LMB96 trial for intermediate risk B-cell nonHodgkin lymphoma in children and adolescents: it is possible to reduce treatment for the early responding patients.

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15. Clevers HC, Owen MJ. Towards a molecular understanding of T-cell differentiation. Immunol Today 1991;12:8692.

16. Ek T, Mellander L, Andersson B, Abrahamsson J. Immune reconstitution after childhood acute lymphoblastic leukemia is most severely affected in the high risk group.

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17. Abrahamsson J, Marky I, Mellander L. Immunoglobulin levels and lymphocyte response to mitogenic stimulation in children with malignant disease during treatment and follow-up. Acta Paediatr 1995;84:177-182.

18. Mackall CL, Fleisher TA, Brown MR, Andrich MP, Chen CC, Feuerstein IM, et al. Distinctions between CD8+ and CD4+ T-cell regenerative pathways result in prolonged Tcell subset imbalance after intensive chemotherapy. Blood 1997;89:3700-3707.

19. Alanko S, Salmi TT, Pelliniemi TT. Recovery of natural killer cells after chemotherapy for childhood acute lymphoblastic leukemia and solid tumors. Med Pediatr Oncol 1995;24:373-378.

20. Yamada S, Kawai H, Miyagawa Y, Komiyama A. Effect of Radiotherapy on Natural Killer Activity in Childhood Acute Lymphoblastic Leukemia and Lymphoma.

Leukemia and Lymphoma1991;4:343-349.

21. Ault KA, Antin JH, Ginsburg D, Orkin SH, Rappeport JM, Keohan ML, et al. Phenotype of recovering lymphoid cell populations after marrow transplantation. J Exp Med 1985;161:1483-1502.

22. Nilsson A, De Milito A, Engström P, Nordin M, Narita M, Grillner L, et al. Current chemotherapy protocols for childhood acute lymphoblastic leukemia induce loss of humoral immunity to viral vaccination antigens. Pediatrics 2002;109:e91.

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∫ÏÈÓÈÎÔ-ÂȉËÌÈÔÏÔÁÈο ‰Â‰Ô̤ӷ Û ÓÔÛËÏ¢fiÌÂÓ· ·È‰È¿ Ì ÔÍ›· Á·ÛÙÚÂÓÙÂÚ›Ùȉ· ·fi Èfi ƒfiÙ· (1984-2007) O. TÛÈ¿ÙÛÈÔ˘1, √. ¶··ÁÈ·ÓÓÔÔ‡ÏÔ˘1, ∞ÈÎ. ™·Ú·ÓÙÔÔ‡ÏÔ˘1, Ã. ∞ÏÂÍ·Ó‰Ú¿ÙÔ˜1, ¢. K·Ú·Ì·ÍfiÁÏÔ˘2, π. K·‚·ÏÈÒÙ˘1 ¶ÂÚ›ÏË„Ë ∂ÈÛ·ÁˆÁ‹: √ Èfi˜ ƒfiÙ· ·ÔÙÂÏ› ÙËÓ ÈÔ Û˘¯Ó‹ ·ÈÙ›· ÔÍ›·˜ Á·ÛÙÚÂÓÙÂÚ›Ùȉ·˜ ÛÙ· ·È‰È¿. ™ÎÔfi˜ Ù˘ ÌÂϤÙ˘ ‹Ù·Ó Ë ÂÎÙ›ÌËÛË ÙÔ˘ Ê¿ÛÌ·ÙÔ˜ Î·È ÙÔ˘ ÊÔÚÙ›Ô˘ Ù˘ ÓfiÛÔ˘ ÛÙËÓ ÂÚÈÔ¯‹ Ù˘ £ÂÛÛ·ÏÔӛ΢ Ì ‚¿ÛË Ù· ‰Â‰Ô̤ӷ Ù˘ ∫ÏÈÓÈ΋˜ Ì·˜.

YÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ: ªÂ ‚¿ÛË ÂȉÈÎfi ÂÚˆÙËÌ·ÙÔÏfiÁÈÔ ·ÓÙÏ‹ıËÎ·Ó ÛÙÔȯ›· ·fi ·ÛıÂÓ›˜ Ù˘ ÂÚÈfi‰Ô˘ 1984-2007. ∆ËÓ ÂÚ›Ô‰Ô ·˘Ù‹ ÓÔÛËχıËÎ·Ó 2.530 ·ÛıÂÓ›˜ Ì ÔÍ›· Á·ÛÙÚÂÓÙÂÚ›Ùȉ· ·fi Èfi ƒfiÙ· (ÔÌ¿‰· ÌÂϤÙ˘) (ıÂÙÈÎÔ› ÁÈ· Rotazyme test). ∞ÔÙÂϤÛÌ·Ù·: √È 1.374 (54%) ·ÛıÂÓ›˜ ‹Û·Ó ·ÁfiÚÈ·. ∆Ô 58% ‹Û·Ó <24 ÌËÓÒÓ. ™Â ÔÚÈṲ̂Ó˜ ¯ÚÔÓÈΤ˜ ÂÚÈfi‰Ô˘˜ (1989, 1992, 1998, 2002 Î·È 2007) ‹Ù·Ó ·˘ÍË̤ÓÔ˜ Ô ·ÚÈıÌfi˜ Î·È ÂȉÈο ÛÙË ¯ÂÈÌÂÚÈÓ‹ ÂÚ›Ô‰Ô. ∏ ÎÏÈÓÈ΋ ÂÈÎfiÓ· Ù˘ ÓfiÛÔ˘ ‹Ù·Ó ‹È·. ¶˘ÚÂÙfi ÂÌÊ¿ÓÈÛ ÙÔ 80% ÙˆÓ ·ÛıÂÓÒÓ, Ì ̤ÛË ‰È¿ÚÎÂÈ· ÙȘ 2,5 Ë̤Ú˜. ∞›Ì· ÛÙ· ÎfiÚ·Ó· ›¯Â ÙÔ 8% ÙˆÓ ·ÛıÂÓÒÓ. µ·ÚÈ¿ ·Ê˘‰¿ÙˆÛË (>10%) ›¯Â ÙÔ 1% ÙˆÓ ·ÛıÂÓÒÓ. √ ̤ÛÔ˜ ¯ÚfiÓÔ˜ ÓÔÛËÏ›·˜ ‹Ù·Ó 3,9 Ë̤Ú˜. ∂͈ÂÓÙÂÚÈΤ˜ ÂΉËÏÒÛÂȘ ·ÚÔ˘Û›·Û ÙÔ 22% ÙˆÓ ·ÛıÂÓÒÓ: ·ÓÒÙÂÚÔ ·Ó·Ó¢ÛÙÈÎfi 14%, ÂÍ¿ÓıËÌ· 9%. ∂ÈÏÔΤ˜ ·ÚÔ˘Û›·Û·Ó 111 ·ÛıÂÓ›˜ (4,4%): Û·ÛÌÔ› 91, ‰˘Û·ÓÔ¯‹ ÛÙË Ï·ÎÙfi˙Ë 51, ˘ÔÓ·ÙÚÈ·ÈÌ›· 12, ·ÏÏÂÚÁ›· ÛÙÔ Á¿Ï· ·ÁÂÏ¿‰·˜ 11, ÂÈÎfiÓ· ÔÍ›·˜ ÎÔÈÏ›·˜ 9, ÂÁÎÂÊ·Ï›Ùȉ· 3, ¿ÛËÙË ÌËÓÈÁÁ›Ùȉ· 2, ÛËÙÈ΋ Û˘Ó‰ÚÔÌ‹ 1, Ô˘Ú·ÈÌÈÎfi-·ÈÌÔÏ˘ÙÈÎfi Û‡Ó‰ÚÔÌÔ 1. ŒÓ·˜ ·ÛıÂÓ‹˜ ËÏÈΛ·˜ 1,5 ¯ÚfiÓˆÓ Ì ÙÚÈۈ̛· 21 Î·È ÛËÙÈ΋ ηٿÛÙ·ÛË Î·Ù¤ÏËÍÂ. ™˘ÌÂÚ¿ÛÌ·Ù·: ∏ ÔÍ›· Á·ÛÙÚÂÓÙÂÚ›Ùȉ· ·fi Èfi ƒfiÙ· Â›Ó·È ‹È· Î·È ÂÔ¯È΋ ÓfiÛÔ˜. ∏ ÂÈÛ·ÁˆÁ‹ Û ÓÔÛÔÎÔÌÂ›Ô Â›Ó·È Û˘Ó‹ıˆ˜ ‚Ú·¯Â›·˜ ‰È¿ÚÎÂÈ·˜, ÂÓÒ ÔÈ ÛÔ‚·Ú¤˜ ÂÈÏÔΤ˜ ‰ÂÓ Â›Ó·È Û˘Ó‹ıÂȘ.

1 ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, ¡ÔÛÔÎÔÌÂ›Ô ∂ȉÈÎÒÓ ¶·ı‹ÛˆÓ, £ÂÛÛ·ÏÔÓ›ÎË 2 ªÈÎÚÔ‚ÈÔÏÔÁÈÎfi ∂ÚÁ·ÛÙ‹ÚÈÔ, ¡ÔÛÔÎÔÌÂ›Ô ∂ȉÈÎÒÓ ¶·ı‹ÛˆÓ, £ÂÛÛ·ÏÔÓ›ÎË AÏÏËÏÔÁÚ·Ê›·: π. ∫·‚·ÏÈÒÙ˘ kavagrc@gmail.com ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, ¡ÔÛÔÎÔÌÂ›Ô ∂ȉÈÎÒÓ ¶·ı‹ÛÂˆÓ °Ú. §·ÌÚ¿ÎË 13, T.K. 546 38, £ÂÛÛ·ÏÔÓ›ÎË

§¤ÍÂȘ ÎÏÂȉȿ: ƒÔÙ·˚fi˜, ÏÔÈÌÒÍÂȘ, Á·ÛÙÚÂÓÙÂÚ›Ùȉ·, ·È‰È¿.

Clinico-epidemiological data on children hospitalized with acute gastroenteritis due to rotavirus (1984-2007) O. Tsiatsiou1, √. Papagiannopoulou1, Aik. Sarantopoulou1, C. Alexandratos1, D. Karabaxoglou2, π. Kavaliotis1 Abstract Background: Rotavirus is one of the most important causes of acute gastroenteritis in infancy. The purpose of the study was to evaluate the burden of the disease in the Thessaloniki region, based on admission data.

Methods: The charts of hospitalized patients for the period 1984-2007 were identified by diagnosis codes and reviewed retrospectively. During the study period 2,530 children with rotavirus gastroenteritis (positive for stool Rotazyme test) were hospitalized. Information was recorded for several variables: demographic data, clinical features, biochemical findings, complications, etc.

Results: Of the patients in the study group, 1,374 (54%) were male and 58% were aged <24 months. An increased number of cases was observed in the years 1989, 1992, 1998, 2002 and 2007, and in the months from December to May. The clinical picture of the disease was mild. Fever developed in 80% of the patients, with a mean duration of 2.5 days. Blood in the stool was observed in the 8% Ôf the cases, and only 1% had severe dehydration. The mean hospitalization was 3.9 days. Extraintestinal manifestations were observed in 22% of the patients, and specifically upper respiratory system symptoms in 14% and rash in 9%. Complications developed in 111 patients (4.4%): seizures 91, lactose intolerance 51, hyponatraemia 12, milk protein allergy 11, picture of acute abdomen 9, encephalitis 3, aseptic meningitis 2, sepsis 1, haemolytic-uraemic syndrome 1. One patient aged 1.5 years with trisomy 21 and a sepsis-like syndrome died.

Conclusions: Acute gastroenteritis caused by Rotavirus is a seasonal disease with mild, acute symptoms.

When admission to hospital is necessary, this is for a short period of time. Complications are not common and usually not serious.

1 Department of Paediatrics, Infectious Diseases Hospital, Thessaloniki 2 Microbiological Laboratory, Infectious Diseases Hospital, Thessaloniki Correspondence: π. ∫avaliotis kavagrc@gmail.com Department of Paediatrics, Infectious Diseases Hospital 13 Gr. Lambraki St., 546 38, Thessaloniki, Greece

Key words: Rotavirus, infectious diseases, gastroenteritis, children. ¶·È‰È·ÙÚÈ΋ 2008;71:301-303

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O. TÛÈ¿ÙÛÈÔ˘ Î·È Û˘Ó.

∂ÈÛ·ÁˆÁ‹ √ Èfi˜ ƒfiÙ· Â›Ó·È ·fi Ù· Û˘¯ÓfiÙÂÚ· ·›ÙÈ· ÔÍ›·˜ Á·ÛÙÚÂÓÙÂÚ›Ùȉ·˜ ‰ÈÂıÓÒ˜, ÚÔÛ‚¿ÏÏÔÓÙ·˜ ηÙÂÍÔ¯‹Ó ‚Ú¤ÊË. ¶·ÁÎÔÛÌ›ˆ˜, ·Ú·ÙËÚÔ‡ÓÙ·È ÂÚÈÛÛfiÙÂÚ˜ ·fi 125 ÂηÙÔÌ̇ÚÈ· ÂÚÈÙÒÛÂȘ ÂÙËÛ›ˆ˜ Ì ÂÚ›Ô˘ 400.000-600.000 ı·Ó¿ÙÔ˘˜, ÔÈ Ôԛ˜ fï˜ ·ÊÔÚÔ‡Ó ÛÙËÓ ÏÂÈÔÓfiÙËÙ¿ ÙÔ˘˜ ˘Ô·Ó¿Ù˘ÎÙ˜ ¯ÒÚ˜ (1,2). ™ÙËÓ ∂˘ÚÒË, Ë Â›ÙˆÛË Ù˘ ÔÍ›·˜ Á·ÛÙÚÂÓÙÂÚ›Ùȉ·˜ Â›Ó·È Î˘Ú›ˆ˜ ÔÈÎÔÓÔÌÈ΋, ‰ÈfiÙÈ Ë ÔÚ›· Ù˘ ÓfiÛÔ˘ Â›Ó·È ÌÂÓ ‹È·, ·ÏÏ¿ Ë Û˘¯ÓfiÙËÙ· ÌÂÁ¿ÏË, Û˘Ì‚¿ÏÏÔÓÙ·˜ ¤ÙÛÈ ÛÙËÓ ÔÈÎÔÓÔÌÈ΋ ÂÈ‚¿Ú˘ÓÛË ÙˆÓ Û˘ÛÙËÌ¿ÙˆÓ ˘Á›·˜ (3,4). ™ÎÔfi˜ Ù˘ ÌÂϤÙ˘ ‹Ù·Ó Ë ÂÎÙ›ÌËÛË Ù˘ Á·ÛÙÚÂÓÙÂÚ›Ùȉ·˜ ·fi Èfi ƒfiÙ· ÛÙËÓ ÂÚÈÔ¯‹ Ù˘ £ÂÛÛ·ÏÔӛ΢ Ì ‚¿ÛË Ù· ‰Â‰Ô̤ӷ Ù˘ ∫ÏÈÓÈ΋˜ Ì·˜. ∏ ÁÓÒÛË ÙˆÓ ÂȉËÌÈÔÏÔÁÈÎÒÓ ‰Â‰ÔÌ¤ÓˆÓ Â›Ó·È ¿ÓÙ· ¯Ú‹ÛÈÌË, ȉȷ›ÙÂÚ· Û ÂÚÈfi‰Ô˘˜ ÂÈÛ·ÁˆÁ‹˜ Ó¤ˆÓ ÂÌ‚ÔÏ›ˆÓ, fiˆ˜ Û˘Ì‚·›ÓÂÈ ÙÒÚ· Ì ÙËÓ ÂÈÛ·ÁˆÁ‹ ÂÌ‚ÔÏ›Ô˘ ηٿ ÙÔ˘ ÈÔ‡ ƒfiÙ· ÛÙË ¯ÒÚ· Ì·˜. ÀÏÈÎfi Î·È Ì¤ıÔ‰ÔÈ ¶ÂÚÈÔ¯‹ ÌÂϤÙ˘. ∏ ÌÂϤÙË ·ÊÔÚ¿ ÙË µfiÚÂÈ· ∂ÏÏ¿‰·, ÌÈ· ÂÚÈÔ¯‹ Ì ÏËı˘ÛÌfi ÂÚ›Ô˘ 3.000.000.

TÔ ¡ÔÛÔÎÔÌÂ›Ô Ì·˜ ·ÔÙÂÏ› ÙÔ Î‡ÚÈÔ Î¤ÓÙÚÔ fiÔ˘ ·ÔÛÙ¤ÏÏÔÓÙ·È ÔÈ ·ÛıÂÓ›˜ Ì ÔÍ›· Á·ÛÙÚÂÓÙÂÚ›Ùȉ·. √Ì¿‰· ÌÂϤÙ˘. ∞ÊÔÚ¿ ·È‰È¿ Ì ÔÍ›· Á·ÛÙÚÂÓÙÂÚ›Ùȉ· ·fi Èfi ƒfiÙ· Ô˘ ÓÔÛËχıËÎ·Ó ÛÙËÓ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ ÙÔ˘ ¡ÔÛÔÎÔÌ›Ԣ ÙËÓ ÂÚ›Ô‰Ô 1984-2007. ∆ËÓ ÂÚ›Ô‰Ô ·˘Ù‹ ÓÔÛËχıËÎ·Ó 16.137 ÂÚÈÙÒÛÂȘ ÔÍ›·˜ Á·ÛÙÚÂÓÙÂÚ›Ùȉ·˜ (ÁÓˆÛÙ‹˜ Î·È ¿ÁÓˆÛÙ˘ ·ÈÙÈÔÏÔÁ›·˜). ™Â 2.530 ·ÛıÂÓ›˜, Ë Ïԛ̈ÍË ÔÊÂÈÏfiÙ·Ó ÛÙÔÓ Èfi ƒfiÙ· (ÔÌ¿‰· ÌÂϤÙ˘). ªÂ ‚¿ÛË ÂȉÈÎfi ÂÚˆÙËÌ·ÙÔÏfiÁÈÔ ·Ó·ÛÎÔ‹ıËÎ·Ó ÔÈ Ê¿ÎÂÏÔÈ ÙˆÓ ·ÛıÂÓÒÓ Î·È ·ÓÙÏ‹ıËÎ·Ó ‰ËÌÔÁÚ·ÊÈο, ÎÏÈÓÈο Î·È ÂÚÁ·ÛÙËÚȷο ÛÙÔȯ›·. ∫ÚÈÙ‹ÚÈ· ÂÈÛ·ÁˆÁ‹˜ ÛÙË ÌÂϤÙË ‹Û·Ó: 1. ™˘ÌÙÒÌ·Ù· Î·È ÛËÌ›· ÔÍ›·˜ Á·ÛÙÚÂÓÙÂÚ›Ùȉ·˜ ‰È¿ÚÎÂÈ·˜ οو ÙˆÓ 15 ËÌÂÚÒÓ. 2. £ÂÙÈÎfi Rotazyme test ÛÙ· ÎfiÚ·Ó·. ∫·ıfiÏË ÙËÓ ÂÚ›Ô‰Ô Ù˘ ÌÂϤÙ˘ ¯ÚËÛÈÌÔÔÈ‹ıËΠÙÔ ›‰ÈÔ test.

∞ÔÙÂϤÛÌ·Ù· ∫·Ù¿ ÙËÓ ÂÚ›Ô‰Ô ÌÂϤÙ˘ ÓÔÛËχıËÎ·Ó 2.530 ·ÛıÂÓ›˜ Ì ÔÍ›· Á·ÛÙÚÂÓÙÂÚ›Ùȉ· ·fi Èfi ƒfiÙ·.

¶ÂÚÈÙÒÛÂȘ ¡Ô.

300 250

¶›Ó·Î·˜ 1. ™ËÌ›· Î·È Û˘ÌÙÒÌ·Ù· Û ·ÛıÂÓ›˜ Ì ÔÍ›· Á·ÛÙÚÂÓÙÂÚ›Ùȉ· ·fi Èfi ƒfiÙ·

¢È¿ÚÚÔÈ· ñ À‰·Ú‹˜ ñ µÏÂÓÓ҉˘ ñ ∞ÈÌÔÚÚ·ÁÈ΋ ŒÌÂÙÔÈ ¶˘ÚÂÙfi˜ ∫ÔÈÏȷο ¿ÏÁË ∞Ê˘‰¿ÙˆÛË >10% ∂͈ÂÓÙÂÚÈΤ˜ ÂΉËÏÒÛÂȘ ñ ƒÈÓ›Ùȉ· - µ‹¯·˜ ñ ∂Í¿ÓıËÌ·

No.

%

2416 1846 1543 202 2264 2024 177 25 632 354 227

95 73 61 8 88 80 7 1 25 14 9

√È 1.374 (54%) ·ÛıÂÓ›˜ ‹Û·Ó ·ÁfiÚÈ·, ÂÓÒ ÙÔ 58% ‹Û·Ó <24 ÌËÓÒÓ. ∏ ÂÙ‹ÛÈ· ηٷÓÔÌ‹ (∂ÈÎfiÓ· 1) ‰Â›¯ÓÂÈ ·˘ÍË̤ÓÔ ·ÚÈıÌfi ÂÚÈÛÙ·ÙÈÎÒÓ ÁÈ· Ù· ¤ÙË 1989, 1992, 1998, 2002 Î·È 2007. ∏ Âԯȷ΋ ηٷÓÔÌ‹ (∂ÈÎfiÓ· 2) ‰Â›¯ÓÂÈ ·˘ÍË̤ÓË Û˘¯ÓfiÙËÙ· ÙËÓ ÂÚ›Ô‰Ô ¢ÂÎÂÌ‚Ú›Ô˘-ª·˝Ô˘. ∏ ÎÏÈÓÈ΋ ÂÈÎfiÓ· Ù˘ ÓfiÛÔ˘ ‹Ù·Ó ‹È·. ∆Ô 80% ÙˆÓ ·ÛıÂÓÒÓ ·ÚÔ˘Û›·Û ˘ÚÂÙfi ̤Û˘ ‰È¿ÚÎÂÈ·˜ (ηٿ ÙË ÓÔÛËÏ›·) 2,5 ËÌÂÚÒÓ (¶›Ó·Î·˜ 1). ∞›Ì· ÛÙ· ÎfiÚ·Ó· ÂÌÊ¿ÓÈÛ ÙÔ 8% ÙˆÓ ·ÛıÂÓÒÓ. ™Ô‚·Ú‹ ·Ê˘‰¿ÙˆÛË >10% ›¯Â ÙÔ 1% ÙˆÓ ·ÛıÂÓÒÓ. ∏ ̤ÛË ‰È¿ÚÎÂÈ· ÓÔÛËÏ›·˜ ‹Ù·Ó 3,9 Ë̤Ú˜, ÂÓÒ Ë Û˘ÓÔÏÈ΋ ̤ÛË ‰È¿ÚÎÂÈ· ÓfiÛÔ˘ 8,4 Ë̤Ú˜. ∆· ÂÚÁ·ÛÙËÚȷο Â˘Ú‹Ì·Ù· ‰ÂÓ ¤‰ÂÈÍ·Ó Î¿ÙÈ ÙÔ È‰È·›ÙÂÚÔ (¶›Ó·Î·˜ 2). ∂͈ÂÓÙÂÚÈΤ˜ ÂΉËÏÒÛÂȘ ·Ú·ÙËÚ‹ıËÎ·Ó Û 566 ·ÛıÂÓ›˜ (22%): ·ÓÒÙÂÚÔ ·Ó·Ó¢ÛÙÈÎfi Û‡ÛÙËÌ· 14%, ÂÍ¿ÓıËÌ· 9%. √È ÂΉËÏÒÛÂȘ ·˘Ù¤˜ ‰ÂÓ ·Ô‰fiıËÎ·Ó Û ¿ÏÏ· ·›ÙÈ·. ∂ÈÏÔΤ˜ ·ÚÔ˘Û›·Û·Ó 111 ·ÛıÂÓ›˜ (4,4%): Û·ÛÌÔ› 91, ‰˘Û·ÓÔ¯‹ ÛÙË Ï·ÎÙfi˙Ë 51, ˘ÔÓ·ÙÚÈ·ÈÌ›· 12, ·ÏÏÂÚÁ›· ÛÙÔ Á¿Ï· ·ÁÂÏ¿‰·˜ 11, ÂÈÎfiÓ· ÔÍ›·˜ ÎÔÈÏ›·˜ 9, ÂÁÎÂÊ·Ï›Ùȉ· 3, ¿ÛËÙË ÌËÓÈÁÁ›Ùȉ· 2, ÛËÙÈ΋ Û˘Ó‰ÚÔÌ‹ 1, Ô˘Ú·ÈÌÈÎfi-·ÈÌÔÏ˘ÙÈÎfi Û‡Ó‰ÚÔÌÔ 1. ŒÓ·˜ ·ÛıÂÓ‹˜ ËÏÈΛ·˜ 1,5 ¯ÚfiÓˆÓ Ì ÛËÙÈ΋ Û˘Ó‰ÚÔÌ‹ (‰ÂÓ ·ÔÌÔÓÒıËΠÌÈÎÚÔÔÚÁ·ÓÈÛÌfi˜) Î·È Û‡Ó‰ÚÔÌÔ Down η٤ÏËÍÂ.

200

¶›Ó·Î·˜ 2. ∂ÚÁ·ÛÙËÚȷο Â˘Ú‹Ì·Ù· Û ·ÛıÂÓ›˜ Ì ÔÍ›· Á·ÛÙÚÂÓÙÂÚ›Ùȉ· ·fi Èfi ƒfiÙ·

150 100

ª¤ÛË ÙÈÌ‹ (‡ÚÔ˜)

50 19 1984 19 85 1986 1987 1988 8 19 9 19 90 1991 1992 1993 1994 19 95 19 96 1997 1998 9 20 9 20 00 2 00 1 2002 2003 2004 20 05 2 00 6 07

0

ŒÙË ∂ÈÎfiÓ· 1. ∂Ù‹ÛÈ· ηٷÓÔÌ‹ ·ÛıÂÓÒÓ Ì ÔÍ›· Á·ÛÙÚÂÓÙÂÚ›Ùȉ· ·fi Èfi ƒfiÙ· (1984-2007).

Paediatriki 2008;71:301-303

§Â˘Î¿ Îί √˘‰ÂÙÂÚfiÊÈÏ· % ∞ÈÌÔÂÙ¿ÏÈ· Îί ¡a mEq/L K mEq/L √˘Ú›· mg/dl ∆∫∂ mm (1Ë ÒÚ·)

9.615 (4.200-18.000) 46 (15-60) 369.872 (280.000-400.000) 139 (130-148) 4,5 (3,5-4,9) 41 (32-68) 31 (18-75)

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¶ÂÚÈÙÒÛÂȘ ¡Ô.

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™ÙË ÌÂϤÙË Ì·˜, Ë Ïԛ̈ÍË ·fi Èfi ƒfiÙ· ‹Ù·Ó ‹È· ÌÂ Û˘¯Ó¤˜ ·ÏÏ¿ fi¯È ÛÔ‚·Ú¤˜ ÂÈÏÔΤ˜. ÷ڷÎÙËÚÈÛÙÈο, ÌfiÓÔ ÙÔ 1% ÙˆÓ ·ÛıÂÓÒÓ ·ÚÔ˘Û›·Û ·Ê˘‰¿ÙˆÛË >10% Î·È ÌfiÓÔ ¤Ó·˜ ı¿Ó·ÙÔ˜ ·Ú·ÙËÚ‹ıËΠ۠ÂÚ›Ô‰Ô 24 ÂÙÒÓ. √ ı¿Ó·ÙÔ˜ ·ÊÔÚÔ‡Û ·È‰› Ì ۇӉÚÔÌÔ Down Î·È ÛËÙÈ΋ Û˘Ó‰ÚÔÌ‹. √È Â͈ÂÓÙÂÚÈΤ˜ ÂΉËÏÒÛÂȘ Ì¿ÏÈÛÙ· ·ÚÔ˘Û›·˙·Ó ¯·ÌËÏfiÙÂÚ· ÔÛÔÛÙ¿ ·fi ·Ó¿ÏÔÁË ÂÏÏËÓÈ΋ ÌÂϤÙË (11). ∆· ÛÙÔȯ›· Ù˘ ÌÂϤÙ˘ Ì·˜ ÈÛÙ‡ԢÌ fiÙÈ ı· ‚ÔËı‹ÛÔ˘Ó ÛÙË ‰È·ÌfiÚʈÛË ÛÙÚ·ÙËÁÈ΋˜ ÁÈ· ÙËÓ ÂÊ·ÚÌÔÁ‹ ÂÌ‚ÔÏÈ·ÛÌÔ‡ ηٿ ÙÔ˘ ÈÔ‡ ƒfiÙ· ÛÙË ¯ÒÚ· Ì·˜.

∂ÈÎfiÓ· 2. ∂Ô¯È΋ ηٷÓÔÌ‹ ·ÛıÂÓÒÓ Ì ÔÍ›· Á·ÛÙÚÂÓÙÂÚ›Ùȉ· ·fi Èfi ƒfiÙ·.

µÈ‚ÏÈÔÁÚ·Ê›·

™˘˙‹ÙËÛË O Èfi˜ ƒfiÙ· Â›Ó·È Ë Î‡ÚÈ· ·ÈÙ›· ÔÍ›·˜ Á·ÛÙÚÂÓÙÂÚ›Ùȉ·˜ ‰ÈÂıÓÒ˜, Ë ÔÔ›· ÛÙȘ ÂÚÈÛÛfiÙÂÚ˜ ¯ÒÚ˜ Ô‰ËÁ› Û ۇӉÚÔÌ· ·Ê˘‰¿ÙˆÛ˘ (5). ∏ Ïԛ̈ÍË Â›Ó·È Û˘¯ÓfiÙÂÚË Î·È ÛÔ‚·ÚfiÙÂÚË Û ·È‰È¿ οو ÙˆÓ 2 ¯ÚfiÓˆÓ (6). ∏ ËÏÈΛ· ·˘Ù‹ ‹Ù·Ó Î·È Ë Î‡ÚÈ· ËÏÈΛ· ÚÔÛ‚ÔÏ‹˜ Î·È ÛÙË ÌÂϤÙË Ì·˜. π‰È·›ÙÂÚÔ ¯·Ú·ÎÙËÚÈÛÙÈÎfi Ù˘ Ïԛ̈͢ ·fi Èfi ƒfiÙ· Â›Ó·È Ë ÌÂÁ¿ÏË Û˘¯ÓfiÙËÙ· ÙˆÓ ÂÌ¤ÙˆÓ (2,3). ∞˘Ùfi Ô‰ËÁ› Û ÈÔ Û˘¯Ó‹ ÂÓ‰ÔÊϤ‚È· ¯ÔÚ‹ÁËÛË ˘ÁÚÒÓ Î·È ËÏÂÎÙÚÔÏ˘ÙÒÓ, ·ÎfiÌË Î·È Û ·ÛıÂÓ›˜ Ì ÌË ÛÔ‚·Ú‹ ·Ê˘‰¿ÙˆÛË. ∏ ‚·Ú‡ÙËÙ· Ù˘ Á·ÛÙÚÂÓÙÂÚ›Ùȉ·˜ ·fi Èfi ƒfiÙ· ÔÈΛÏÏÂÈ (5). ∂›Ó·È ÈÔ ÛÔ‚·Ú‹ ÛÙË ‚ÚÂÊÈ΋ ËÏÈΛ·, fiˆ˜ Û˘Ì‚·›ÓÂÈ Ì ÔÏϤ˜ ÏÔÈÌÒÍÂȘ. ªÂÚÈÎÔ› ıˆÚÔ‡Ó fiÙÈ ÛÙË Û˘ÁÎÂÎÚÈ̤ÓË ÂÚ›ÙˆÛË ˘¿Ú¯ÂÈ ·ÈÙÈÔÏÔÁÈ΋ ·Ú¿ ËÏÈÎȷ΋ Û¯¤ÛË (7). ™ÙȘ ·Ó·Ù˘ÛÛfiÌÂÓ˜ ¯ÒÚ˜, Ë ÎÏÈÓÈ΋ ÂÈÎfiÓ· Â›Ó·È ‚·Ú‡ÙÂÚË Î·È ÔÈ Û˘Ó¤ÂȘ ÛÔ‚·ÚfiÙÂÚ˜. ªÂÁ·Ï‡ÙÂÚÔ Ê˘ÛÈο Â›Ó·È Î·È ÙÔ ÔÛÔÛÙfi ı·Ó¿ÙˆÓ (8). ™ÙȘ ·ÓÂÙ˘Á̤Ó˜ ¯ÒÚ˜, Ë Â›ÙˆÛË Â›Ó·È Î˘Ú›ˆ˜ ÔÈÎÔÓÔÌÈ΋ Î·È Û¯ÂÙ›˙ÂÙ·È Ì ÙÔ ˘„ËÏfi ÔÛÔÛÙfi ÂÈÛ·ÁˆÁ‹˜ ÙˆÓ ·Û¯fiÓÙˆÓ Û ÓÔÛÔÎÔÌÂ›Ô (3). ÷ڷÎÙËÚÈÛÙÈο ÛÙËÓ ∞˘ÛÙÚ·Ï›·, ÌÈ· ·ÓÂÙ˘Á̤ÓË ¯ÒÚ· Ì ÌÂÁ¿ÏË ÁˆÁÚ·ÊÈ΋ ¤ÎÙ·ÛË, ‰È·ÈÛÙÒıËΠfiÙÈ ÛÙȘ ÂÚÈÔ¯¤˜ fiÔ˘ ˘¿Ú¯Ô˘Ó ·˘Ùfi¯ıÔÓ˜ ÙÔ ÔÛÔÛÙfi ÂÈÛ·ÁˆÁ‹˜ ·È‰ÈÒÓ Ì Á·ÛÙÚÂÓÙÂÚ›Ùȉ· ·fi Èfi ƒfiÙ· Â›Ó·È ˘„ËÏfi, Ë ËÏÈΛ· ÂÈÛ·ÁˆÁ‹˜ ÌÈÎÚfiÙÂÚË Î·È Ô ¯ÚfiÓÔ˜ ·Ú·ÌÔÓ‹˜ ÛÙÔ ÓÔÛÔÎÔÌÂ›Ô ÌÂÁ·Ï‡ÙÂÚÔ˜ (9,10).

1. Feigin RD, Cherry JD, Demmler GJ, Kaplan S, editors.

Textbook of Pediatric Infectious Diseases. 5th ed. Philadelphia, PA: WB Saunders Co.; 2004.

2. Jenson HB, Baltimore RS, editors. Pediatric Infectious Diseases. 2nd ed. Philadelphia: WB Saunders Co.; 2002.

3. Parashar UD, Hummelman EG, Bresee JS, Miller MA, Glass RI. Global illness and deaths caused by rotavirus disease in children. Emerg Infect Dis 2003;9:565-572.

4. The Pediatric ROTavirus European CommitTee (PROTECT).

The paediatric burden of rotavirus disease in Europe. Epidemiol Infect 2006;134:908-916.

5. Parashar UD, Alexander JP, Glass RI; Advisory Committee on Immunization Practices (ACIP), Centers for Disease Control and Prevention (CDC). Prevention of rotavirus gastroenteritis among infants and children. Recommendations of the Advisory Committee on Immunization Practice (ACIP). MMWR Recomm Rep 2006; 55:1-13.

6. Haffejee IE. The epidemiology of rotavirus infections: a global perspective. J Pediatr Gastroenterol Nutr 1995;20:275-286.

7. Albano F, Bruzzese E, Bella A, Cascio A, Titone L, Arista S, et al. Rotavirus and not age determines gastroenteritis severity in children: a hospital-based study. Eur J Pediatr. 2007;166: 241-247.

8. Khuri-Bulos N, Al Khatib M. Importance of rotavirus as a cause of gastroenteritis in Jordan: a hospital based study.

Scand J Infect Dis 2006;38:639-644.

9. Schultz R. Rotavirus gastroenteritis in the Northern Territory, 1995-2004. Med J Aust 2006;185:354-356.

10. Newall AT, MacIntyre R, Wang H, ∏ull B, Macartney K. Burden of severe rotavirus disease in Australia. J Paediatr Child Health 2006;42:521-527.

11. ¶Ú›ÊÙ˘ K, ∫·ÓÂÏÏÔÔ‡ÏÔ˘ ª, ÷ÓÔ‡ÌË ª, ª·Ï¿ÌÔ˘§·‰¿ ∂, ÷ȉ¿˜ ∞. √Í›· Á·ÛÙÚÂÓÙÂÚ›Ùȉ· ·fi Rota Èfi Î·È ÂΉËÏÒÛÂȘ ·fi ÙÔ ·Ó·Ó¢ÛÙÈÎfi. ¶·È‰È·ÙÚÈ΋ 1989:52; 148-156.

¶·È‰È·ÙÚÈ΋ 2008;71:301-303

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PRACTICAL ISSUE

™‡Ó‰ÚÔÌÔ ·ÈÊÓ›‰ÈÔ˘ ‚ÚÂÊÈÎÔ‡ ı·Ó¿ÙÔ˘: ¶·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ Î·È ÓÂÒÙÂÚ˜ ηÙ¢ı˘ÓÙ‹ÚȘ Ô‰ËÁ›Â˜ µ’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, “µÂÓÈ˙¤ÏÂÈÔ” °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô ∏Ú·ÎÏ›Ԣ

™. ™ÙÂÊ·Ó¿ÎË, ∞. ∆ÛÈÏÈÌÈÁοÎË

AÏÏËÏÔÁÚ·Ê›·: AÌ·Ï›· ∆ÛÈÏÈÌÈÁοÎË tsilimam@yahoo.gr µ’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, “µÂÓÈ˙¤ÏÂÈÔ” °ÂÓÈÎfi ¡ÔÛÔÎÔÌÂ›Ô ∏Ú·ÎÏ›Ԣ

‚Ú¤ÊÔ˘˜ ËÏÈΛ·˜ 1 ÌËÓfi˜-1 ¤ÙÔ˘˜. ™˘Ó‹ıˆ˜, Û˘Ì‚·›ÓÂÈ Û ÚÔËÁÔ‡ÌÂÓ· ˘ÁÈ‹ ‚Ú¤ÊË Î·È Ë ·ÈÙ›· ÙÔ˘ ı·Ó¿ÙÔ˘ ·Ú·Ì¤ÓÂÈ ·ÓÂÍ‹ÁËÙË, ·Ú¿ ÙÔÓ ÂÓ‰Âϯ‹ ¤ÏÂÁ¯Ô Ô˘ ÂÚÈÏ·Ì‚¿ÓÂÈ Ï‹ÚË ·˘ÙÔ„›·, ÂͤٷÛË ÙˆÓ Û˘ÓıËÎÒÓ ı·Ó¿ÙÔ˘ Î·È ·Ó·ÛÎfiËÛË ÙÔ˘ ÎÏÈÓÈÎÔ‡ ÈÛÙÔÚÈÎÔ‡ ÙÔ˘ ‚Ú¤ÊÔ˘˜. ∂›Ó·È ÌÈ· ‰È·Ù·Ú·¯‹ ÛÙËÓ ÔÔ›· ·›˙Ô˘Ó ÚfiÏÔ ÁÂÓÂÙÈÎÔ›, ÂÚÈ‚·ÏÏÔÓÙÈÎÔ› Î·È Û˘ÌÂÚÈÊÂÚÈÔÏÔÁÈÎÔ›/ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈÎÔ› ·Ú¿ÁÔÓÙ˜. ∏ ∞ÌÂÚÈηÓÈ΋ ∞η‰ËÌ›· ¶·È‰È·ÙÚÈ΋˜ ·Ó·ÎÔ›ÓˆÛ ÙÔ 2005 ÙȘ ÙÂÏÂ˘Ù·›Â˜ Ô‰ËÁ›Â˜ ÁÈ· ÙË Ì›ˆÛË Ù˘ Â›ÙˆÛ˘ ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ·ÈÊÓ›‰ÈÔ˘ ı·Ó¿ÙÔ˘ Ô˘ Û‹ÌÂÚ· ÊÙ¿ÓÂÈ Û 0,3-0,6/1.000 ÁÂÓÓ‹ÛÂȘ ˙ÒÓÙˆÓ ÓÂÔÁÓÒÓ. √È ·È‰›·ÙÚÔÈ ¤¯Ô˘Ó ˘Ô¯Ú¤ˆÛË Ó· ÂÓËÌÂÚÒÓÔ˘Ó ¤ÁηÈÚ· ÙÔ˘˜ ÁÔÓ›˜ ÁÈ· ÙËÓ ÚfiÏË„Ë ÙÔ˘ SIDS.

¶ÂÚ›ÏË„Ë: ™‡Ó‰ÚÔÌÔ ·ÈÊÓ›‰ÈÔ˘ ‚ÚÂÊÈÎÔ‡ ı·Ó¿ÙÔ˘ (SIDS) ÔÚ›˙ÂÙ·È Ô Í·ÊÓÈÎfi˜, ·ÓÂÍ‹ÁËÙÔ˜ ı¿Ó·ÙÔ˜ ÂÓfi˜

§¤ÍÂȘ ÎÏÂȉȿ: ™‡Ó‰ÚÔÌÔ ·ÈÊÓ›‰ÈÔ˘ ‚ÚÂÊÈÎÔ‡ ı·Ó¿ÙÔ˘, Û˘ÛÙ¿ÛÂȘ ∞ÌÂÚÈηÓÈ΋˜ ∞η‰ËÌ›·˜ ¶·È‰È·ÙÚÈ΋˜.

Sudden infant death syndrome: Risk factors and the latest guidelines 2nd Department of Paediatrics, “Venizeleio” General Hospital of Heraklion Correspondence: Amalia Tsilimigkaki tsilimam@yahoo.gr 2nd Department of Paediatrics, “Venizeleio” General Hospital of Heraklion

S. Stefanaki, A. Tsilimigkaki Abstract: Sudden infant death syndrome (SIDS) is defined as the sudden unexplained death of an infant at the age of 1 month-1 year. It usually occurs in previously healthy infants, and the cause of death remains unexplained despite a thorough case investigation, including complete autopsy, death scene investigation and review of the clinical history. It is a disturbance in which genetic, environmental, and behavioural/ sociocultural factors all play a role. The American Academy of Pediatrics announced in 2005 its latest recommendations for reducing the incidence of SIDS, which today is estimated at 0.3-0.6/1,000 live births.

Individual medical conditions may warrant a physician recommending precautions to parents, after weighing the relative risks and benefits.

Key words: Sudden infant death syndrome, recommendations of American Academy of Pediatrics.

∂ÈÛ·ÁˆÁ‹ ∆Ô Û‡Ó‰ÚÔÌÔ ·ÈÊÓ›‰ÈÔ˘ ‚ÚÂÊÈÎÔ‡ ı·Ó¿ÙÔ˘ ÂÍ·ÎÔÏÔ˘ı› Ó· Â›Ó·È Ë ÚÒÙË ·ÈÙ›· ı·Ó¿ÙÔ˘ Û ˘ÁÈ‹ ÙÂÏÂÈfiÌËÓ· ‚Ú¤ÊË, ËÏÈΛ·˜ 1 ÌËÓfi˜ ¤ˆ˜ 1 ¤ÙÔ˘˜ ÛÙȘ ·ÓÂÙ˘Á̤Ó˜ ¯ÒÚ˜ (1,2). ø˜ Û‡Ó‰ÚÔÌÔ ·ÈÊÓ›‰ÈÔ˘ ‚ÚÂÊÈÎÔ‡ ı·Ó¿ÙÔ˘ (SIDS) ÔÚ›˙ÂÙ·È Ô Í·ÊÓÈÎfi˜ ı¿Ó·ÙÔ˜ ÂÓfi˜ ‚Ú¤ÊÔ˘˜ ËÏÈΛ·˜ οو ÙÔ˘ ¤ÙÔ˘˜ Ô˘ ·Ú·Ì¤ÓÂÈ ·ÓÂÍ‹ÁËÙÔ˜ ‡ÛÙÂÚ· ·fi ÂÓ‰Âϯ‹ ¤ÏÂÁ¯Ô, Ô ÔÔ›Ô˜ ÂÚÈÏ·Ì‚¿ÓÂÈ Ï‹ÚË ·˘ÙÔ„›·, ÂͤٷÛË ÙˆÓ Û˘ÓıËÎÒÓ ı·Ó¿ÙÔ˘ Î·È ·Ó·ÛÎfiËÛË ÙÔ˘ ÎÏÈÓÈÎÔ‡ ÈÛÙÔÚÈÎÔ‡ ÙÔ˘ ‚Ú¤ÊÔ˘˜ (3,4). ∂ȉËÌÈÔÏÔÁ›· ∞Ó Î·È Ë Â›ÙˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ·ÚÔ˘ÛÈ¿˙ÂÈ Ì›· ÌÈÎÚ‹ ·‡ÍËÛË Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·, ˆÛÙfiÛÔ ¤¯ÂÈ ÌÂȈı› ‰Ú·Ì·ÙÈο ÌÂÙ¿ ÙÔ 1992, fiÙ·Ó Ë ∞ÌÂÚÈηÓÈ΋ ∞η‰ËÌ›· ¶·È‰È·ÙÚÈ΋˜ ÍÂΛÓËÛ ÙËÓ Î·Ì¿ÓÈ· ÁÈ· ÙËÓ Î·ıȤڈÛË Ù˘ ‡ÙÈ·˜ ı¤Û˘ ÛÙÔÓ ‡ÓÔ ÁÈ· Ù· ‚Ú¤ÊË. ŒÙÛÈ, Ë Â›ÙˆÛË ·fi 0,8-1,3/1.000 ÁÂÓÓ‹ÛÂȘ Paediatriki 2008;71:304-310

˙ÒÓÙˆÓ ÓÂÔÁÓÒÓ ÙÔ 1990 ˘ÔÏÔÁ›˙ÂÙ·È Û‹ÌÂÚ· Û 0,3-0,6/1.000 (4,5), ÂÓÒ ·ÊÔÚ¿ ÙÔ 25% ÙˆÓ ı·Ó¿ÙˆÓ Û ‚Ú¤ÊË ÌÂٷ͇ 1 ÌËÓfi˜ ¤ˆ˜ 1 ¤ÙÔ˘˜ (1). ™˘Ó‹ıˆ˜ ÂÌÊ·Ó›˙ÂÙ·È Î·Ù¿ ÙÔ˘˜ ¯ÂÈÌÂÚÈÓÔ‡˜ Ì‹Ó˜ ÙÔ˘ ¤ÙÔ˘˜, ÛÙȘ ËÏÈ˘ 2-4 ÌËÓÒÓ, ÛÙ· ·ÁfiÚÈ·, ÛÙÔ ‰Â‡ÙÂÚÔ ‹ ÛÙ· ÂfiÌÂÓ· ·È‰È¿ (1,6).

¶·ıÔÏÔÁÔ·Ó·ÙÔÌ›·-¶·ıÔÊ˘ÛÈÔÏÔÁ›· ¢ÂÓ ˘¿Ú¯Ô˘Ó ÂȉÈο ·ıÔÏÔÁÔ·Ó·ÙÔÌÈο ‹ ·ıÔÊ˘ÛÈÔÏÔÁÈο Â˘Ú‹Ì·Ù· ÛÙ· ı‡Ì·Ù· ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ·ÈÊÓ›‰ÈÔ˘ ‚ÚÂÊÈÎÔ‡ ı·Ó¿ÙÔ˘. ™Â ‚Ú¤ÊË Ô˘ ¤ı·Ó·Ó ·fi SIDS ‚Ú¤ıËÎ·Ó ÛÔ‚·Ú¤˜ ‚Ï¿‚˜ ÛÙÔ˘˜ Ó‡ÌÔÓ˜ Î·È ¿ÏÏ· fiÚÁ·Ó·, fiˆ˜ ÙÔÓ ÂÁΤʷÏÔ. ∞Ó¢ڛÛÎÔÓÙ·È ÂÙ¯ÂÈÒ‰ÂȘ ·ÈÌÔÚÚ·Á›Â˜ ÛÙÔ 68-95% ÙˆÓ ÂÚÈÙÒÛˆÓ, Ó¢ÌÔÓÈ΋ Û˘ÌÊfiÚËÛË ÛÙÔ 89% Î·È Ó¢ÌÔÓÈÎfi Ô›‰ËÌ· ÛÙÔ 63% (1). ™¯Â‰fiÓ ÛÙ· 2/3 ·fi ·˘Ù¿ ‚Ú¤ıËÎ·Ó ÂӉ›ÍÂȘ ÚÔ¸¿Ú¯Ô˘Û·˜ ¯ÚfiÓÈ·˜ ·ÛÊ˘Í›·˜, fiˆ˜ Ô ·ÁÁÂÈ·Îfi˜ ÂÓ‰ÔıËÏÈ·Îfi˜ ·Ú¿ÁÔÓÙ·˜ ·‡ÍËÛ˘

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™‡Ó‰ÚÔÌÔ ·ÈÊÓ›‰ÈÔ˘ ‚ÚÂÊÈÎÔ‡ ı·Ó¿ÙÔ˘

¶›Ó·Î·˜ 1. ¶ÂÚÈ‚·ÏÏÔÓÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· SIDS (1) ∞fi ÙË ÌËÙ¤Ú·

∞fi ÙÔ ‚Ú¤ÊÔ˜

∫¿ÓÈÛÌ· ÃÚ‹ÛË ·ÏÎÔfiÏ ∫·Ù¿¯ÚËÛË Ô˘ÛÈÒÓ (ÔÈÔÂȉÒÓ) ∞ÓÂ·Ú΋˜ ÂÚÈÁÂÓÓËÙÈ΋ ÊÚÔÓÙ›‰· ÷ÌËÏfi ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈÎfi Â›Â‰Ô ªÈÎÚ‹ ËÏÈΛ· ÌËÙ¤Ú·˜ ÷ÌËÏfi ÌÔÚʈÙÈÎfi Â›Â‰Ô ªÔÓÔÁÔÓÂ˚΋ ÔÈÎÔÁ¤ÓÂÈ· ¶ÔÏ˘ÌÂÏ›˜ ÔÈÎÔÁ¤ÓÂȘ ∂Ó‰ÔÌ‹ÙÚÈ· ˘ÔÍ›· ∂Ó‰ÔÌ‹ÙÚÈ· ηı˘ÛÙ¤ÚËÛË ·‡ÍËÛ˘ ªÈÎÚfi ‰È¿ÛÙËÌ· ·Ó¿ÌÂÛ· ÛÙȘ ÂÁ΢ÌÔÛ‡Ó˜

∏ÏÈΛ· (2-4 ÌËÓÒÓ) º‡ÏÔ (·ÁfiÚÈ·) º˘Ï‹/ÂıÓÈÎfiÙËÙ· ªË ¯Ú‹ÛË È›Ï·˜ ÛÙÔÓ ‡ÓÔ ¶ÚÔˆÚfiÙËÙ· ¶ÚËÓ‹˜ ‹ Ï¿ÁÈ· ı¤ÛË ÛÙÔÓ ‡ÓÔ ¶ÚfiÛÊ·ÙË ÂÌ‡ÚÂÙË ÓfiÛÔ˜ ⁄ÓÔ˜ Û ̷Ϸ΋ ÂÈÊ¿ÓÂÈ· £ÂÚÌÈÎfi ÛÙÚ˜/˘ÂÚı¤ÚÌ·ÓÛË ∫¿Ï˘„Ë ÚÔÛÒÔ˘ ·fi ÛÎÂ¿ÛÌ·Ù· ∫ÔÈÓfi ÎÚ‚¿ÙÈ Ì ÁÔÓ›˜ ‹ ·‰¤ÚÊÈ· ⁄ÓÔ˜ ۠ͯˆÚÈÛÙfi ‰ˆÌ¿ÙÈÔ ·fi ÂΛÓÔ ÙˆÓ ÁÔÓÈÒÓ ÃÂÈÌÂÚÈÓÔ› Ì‹Ó˜, ÌË ÎÂÓÙÚÈ΋ ı¤ÚÌ·ÓÛË

(VEGF) ÙÔ˘ ÂÁÎÂÊ·ÏÔÓˆÙÈ·›Ô˘ ˘ÁÚÔ‡ (∂¡À). ∏ ̤ÛË Û˘ÁΤÓÙÚˆÛË ÙÔ˘ VEGF ÛÙÔ ∂¡À ‹Ù·Ó 308 pg/dl ÛÙȘ ÂÚÈÙÒÛÂȘ SIDS, Û˘ÁÎÚÈÓfiÌÂÓË Ì 85 pg/dl ÛÙ· ‚Ú¤ÊË Ô˘ ¤ı·Ó·Ó ·fi ¿ÏÏË ·ÈÙ›· (7). √ Ô˘‰fi˜ ·Ê‡ÓÈÛ˘ Ê·›ÓÂÙ·È Ó· ·›˙ÂÈ ÛËÌ·ÓÙÈÎfi ÚfiÏÔ ÛÙÔ SIDS. ª›· ıˆڛ· ˘ÔÛÙËÚ›˙ÂÈ fiÙÈ Ù· ‚Ú¤ÊË Ô˘ ÎÔÈÌÔ‡ÓÙ·È Û ÚËÓ‹ ı¤ÛË Â›Ó·È ÈÔ Èı·Ófi Ó· ÂÈÛÓ‡ÛÔ˘Ó ÙÔ ÂÎÓÂfiÌÂÓÔ ‰ÈÔÍ›‰ÈÔ ÙÔ˘ ¿Óıڷη Î·È ·˘Ùfi Ô‰ËÁ› Û ˘ÂÚηÓ›·, ˘ÔÍ›· Î·È ı¿Ó·ÙÔ ·Ó Ë ·Ê‡ÓÈÛË ‰ÂÓ Â›Ó·È Î·Ù¿ÏÏËÏË. √ Kinney Î·È ÔÈ Û˘ÓÂÚÁ¿Ù˜ ÙÔ˘ ÂÍ¤Ù·Û·Ó ÂÁÎÂÊ·ÏÈο ÛÙÂϤ¯Ë ‚ÚÂÊÒÓ Ô˘ ¤ı·Ó·Ó ·fi SIDS Î·È ‚Ú‹Î·Ó ‰È·Ù·Ú·¯¤˜ ÛÙË ÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ˘Ô‰Ô¯¤ˆÓ Ù˘ ÛÂÚÔÙÔÓ›Ó˘. Œ¯ÂÈ ·Ô‰Âȯı› Û ·ÚÎÂÙ¤˜ ÌÂϤÙ˜ fiÙÈ ÔÏÏ¿ ·fi Ù· ı‡Ì·Ù· SIDS ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÔÏ˘ÌÔÚÊÈÛÌfi Û ÌÈ· ÂÚÈÔ¯‹ ÙÔ˘ ÁÔÓȉ›Ô˘ Ô˘ ÂϤÁ¯ÂÈ ÙËÓ ÚˆÙ½ÓË ÌÂÙ·ÊÔÚ¿˜ Ù˘ ÛÂÚÔÙÔÓ›Ó˘, ÁÓˆÛÙ‹ ˆ˜ 5-HTT. ∏ Â·ÎfiÏÔ˘ıË ·˘ÍË̤ÓË ‰Ú·ÛÙÈÎfiÙËÙ· ÙÔ˘ ÌÂÙ·ÊÔÚ¤· Ù˘ ÛÂÚÔÙÔÓ›Ó˘ Ô‰ËÁ› Û ÂÏ·Ùو̤ÓË Û˘ÁΤÓÙÚˆÛ‹ Ù˘ ÛÙÔ˘˜ ÙÂÏÈÎÔ‡˜ Ó¢ÚÒÓ˜. ∞˘Ù¤˜ ÔÈ ‰È·Ù·Ú·¯¤˜ ÚÔηÏÔ‡Ó Èı·ÓfiÓ ÙË ‰˘ÛÏÂÈÙÔ˘ÚÁ›· ÛÙËÓ ·Ê‡ÓÈÛË ÛÙ· ‚Ú¤ÊË ·˘Ù¿ (4). ¶ÔÏ˘ÌÔÚÊÈÛÌÔ› ¤¯Ô˘Ó ‚ÚÂı› Î·È Û ¿ÏÏÔ˘˜ ÁfiÓÔ˘˜, fiˆ˜ ÛÙÔÓ SCN5A Ô˘ Û¯ÂÙ›˙ÂÙ·È Ì ÙÔ Û‡Ó‰ÚÔÌÔ ÙÔ˘ Ì·ÎÚÔ‡ QT (7). °ÂÓÂÙÈΤ˜ ÌÂÙ·ÏÏ¿ÍÂȘ ¤¯Ô˘Ó ‚ÚÂı› ÛÙ· ηӿÏÈ· ∫ Î·È ¡· ÛÙȘ ÌÂÌ‚Ú¿Ó˜ ÙˆÓ Ì˘ÔηډȷÎÒÓ Î˘ÙÙ¿ÚˆÓ Ô˘ ÚÔηÏÔ‡Ó ·Ú¿Ù·ÛË ÙÔ˘ QT ‰È·ÛÙ‹Ì·ÙÔ˜ Î·È Ô‰ËÁÔ‡Ó Û SIDS. Œ¯ÂÈ ‚ÚÂı› fiÙÈ 4,3% ÙˆÓ ‚ÚÂÊÒÓ Ô˘ ¤ı·Ó·Ó Ì SIDS ›¯·Ó ÁÂÓÂÙÈΤ˜ ÌÂÙ·ÏÏ¿ÍÂȘ Ô˘ Û¯ÂÙ›˙ÔÓÙ·Ó Ì ÙÔ Û‡Ó‰ÚÔÌÔ ÙÔ˘ Ì·ÎÚÔ‡ QT (8). À¿Ú¯Ô˘Ó Î·È ¿ÏÏÔÈ ÔÏ˘ÌÔÚÊÈÛÌÔ› (PHOX2a, RET, ECE1, TLX3, EN1) Ô˘ ÂËÚ¿˙Ô˘Ó ÙËÓ ·Ó¿Ù˘ÍË ÙÔ˘ ·˘ÙfiÓÔÌÔ˘ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ ÛÙ· ı‡Ì·Ù· SIDS (4). ªÂ ÙËÓ ÚfiÔ‰Ô ÙˆÓ ‰È·ÁÓˆÛÙÈÎÒÓ ·ıÔÏÔÁÔ·Ó·ÙÔÌÈÎÒÓ ÌÂıfi‰ˆÓ Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ·, ÔÏÏ¿

‚Ú¤ÊË Ô˘ ›¯·Ó ıˆÚËı› ı‡Ì·Ù· SIDS ‚Ú¤ıËΠfiÙÈ ¤·Û¯·Ó ·fi ÌÂÙ·‚ÔÏÈο ÓÔÛ‹Ì·Ù·. ∏ ÈÔ Û˘¯Ó‹ ‰È·Ù·Ú·¯‹ ·ÊÔÚÔ‡Û ÙÔ ÌÂÙ·‚ÔÏÈÛÌfi Ù˘ ÔÍ›‰ˆÛ˘ ÙˆÓ ÏÈ·ÚÒÓ ÔͤˆÓ ̤Û˘ Î·È Ì·ÎÚ¿˜ ·Ï‡ÛÔ˘ ·fi ·ÓÂ¿ÚÎÂÈ· ÂÓ˙‡ÌˆÓ, fiˆ˜ Ë ·Î˘Ï-COA ‰Â¸‰ÚÔÁÂÓ¿ÛË Î·È Ù· ‚Ú¤ÊË ·˘Ù¿ ‰ÂÓ Û˘ÌÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ÛÙ· ı‡Ì·Ù· SIDS (8,9).

¶·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· SIDS ∆· ÈÔ ÚfiÛÊ·Ù· ‰Â‰Ô̤ӷ ÁÈ· ÙÔ SIDS (4) ‰Â›¯ÓÔ˘Ó fiÙÈ ÚfiÎÂÈÙ·È ÁÈ· ÌÈ· Û‡ÓıÂÙË ÔÏ˘·Ú·ÁÔÓÙÈ΋ ‰È·Ù·Ú·¯‹ ÛÙËÓ ÔÔ›· ÁÂÓÂÙÈÎÔ›, ÂÚÈ‚·ÏÏÔÓÙÈÎÔ› Î·È Û˘ÌÂÚÈÊÂÚÈÔÏÔÁÈÎÔ›/ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈÎÔ› ·Ú¿ÁÔÓÙ˜ ·›˙Ô˘Ó ÚfiÏÔ, fiˆ˜ ·ÚÔ˘ÛÈ¿˙ÂÙ·È ÛÙËÓ ∂ÈÎfiÓ· 1. √È ÂÚÈ‚·ÏÏÔÓÙÈÎÔ› Î·È ÔÈ ÁÂÓÂÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· SIDS ·Ó·Ê¤ÚÔÓÙ·È ÛÙÔ˘˜ ¶›Ó·Î˜ 1 Î·È 2 Î·È ·Ó·Ï‡ÔÓÙ·È ·Ú·Î¿Ùˆ. ¶·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· SIDS Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙË ÌËÙ¤Ú· Î·È ÙËÓ Î‡ËÛË ∆Ô Î¿ÓÈÛÌ· ÚÔ Î·È ÌÂÙ·ÁÂÓÓËÙÈο Â›Ó·È Ô ∫ÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈÎÔ›, ÂÚÈ‚·ÏÏÔÓÙÈÎÔ›, Û˘ÌÂÚÈÊÂÚÈÔÏÔÁÈÎÔ› ·Ú¿ÁÔÓÙ˜

°ÂÓÂÙÈÎÔ› ·Ú¿ÁÔÓÙ˜

º·ÈÓfiÙ˘Ô˜

SIDS ∂ÈÎfiÓ· 1. ¶·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· SIDS (4). ¶·È‰È·ÙÚÈ΋ 2008;71:304-310

Pediatri Jul-Aug 08

30-07-08

15:53

™ÂÏ›‰·306

306

™. ™ÙÂÊ·Ó¿ÎË, ∞. ∆ÛÈÏÈÌÈÁοÎË

¶›Ó·Î·˜ 2. °ÔÓ›‰È· Û ‚Ú¤ÊË Ì SIDS (1) ∫·Ó·ÏÔ¿ıÂȘ ηډȷÎÒÓ ÈfiÓÙˆÓ ∫·Ó¿ÏÈ· Na ∫·Ó¿ÏÈ· K °ÔÓ›‰ÈÔ Ù˘ ÚˆÙ½Ó˘ ÌÂÙ·ÊÔÚ¤· Ù˘ ÛÂÚÔÙÔÓ›Ó˘ (5-HTT) °ÔÓ›‰È· ·Ó¿Ù˘Í˘ ÙÔ˘ ·˘ÙfiÓÔÌÔ˘ Ó¢ÚÈÎÔ‡ Û˘ÛÙ‹Ì·ÙÔ˜ Paired-like homeobox (Phox2a) Rearranged during transfection (RET) Endothelin-converting enzyme-1 (ECE1) T-cell leukemia homeobox (TLX3) Engrailed-1 (EN1) §Ô›ÌˆÍË Î·È ÊÏÂÁÌÔÓ‹ ™˘Ìϋڈ̷ C4A Î·È C4B πÓÙÂÚÏ¢ΛÓË 10

ÛËÌ·ÓÙÈÎfiÙÂÚÔ˜ ·’ ·˘ÙÔ‡˜. ™Â ÌÂϤÙ˜ Ô˘ Û˘Ó¤ÎÚÈÓ·Ó ÙË Û˘¯ÓfiÙËÙ· ÙÔ˘ SIDS ÚÈÓ Î·È ÌÂÙ¿ ÙËÓ Î·Ì¿ÓÈ· ÁÈ· ÙËÓ ·ÏÏ·Á‹ Ù˘ ı¤Û˘ ÛÙÔÓ ‡ÓÔ, ‚Ú¤ıËΠfiÙÈ Ù· ‚Ú¤ÊË Ô˘ ÔÈ ÌËÙ¤Ú˜ ÙÔ˘˜ οÓÈ˙·Ó ›¯·Ó 3 ÊÔÚ¤˜ ÌÂÁ·Ï‡ÙÂÚË Èı·ÓfiÙËÙ· Ó· Âı¿ÓÔ˘Ó ·fi ·ÈÊÓ›‰ÈÔ ı¿Ó·ÙÔ ·fi ·˘Ù¿ Ô˘ ÔÈ ÌËÙ¤Ú˜ ÙÔ˘˜ ‰ÂÓ Î¿ÓÈ˙·Ó ÚÈÓ ·fi ÙËÓ ÂÊ·ÚÌÔÁ‹ Ù˘ ηÌ¿ÓÈ·˜ Î·È 5 ÊÔÚ¤˜ ÌÂÁ·Ï‡ÙÂÚË ÌÂÙ¿ ÙËÓ ÂÊ·ÚÌÔÁ‹ Ù˘ (1). √ ΛӉ˘ÓÔ˜ SIDS ·fi ¤ÎıÂÛË Û ηÓfi ÌÂÙ·ÁÂÓÓËÙÈο ·˘Í¿ÓÂÈ, fiÛÔ ÌÂÁ·Ï‡ÙÂÚÔ˜ Â›Ó·È Ô ·ÚÈıÌfi˜ ÙˆÓ ·ÙfiÌˆÓ Ô˘ ηÓ›˙Ô˘Ó ÛÙÔ Û›ÙÈ, fiÛÔ ÌÂÁ·Ï‡ÙÂÚÔ˜ Â›Ó·È Ô ·ÚÈıÌfi˜ ÙˆÓ ÙÛÈÁ¿ÚˆÓ Î·È fiÛÔ ÌÂÁ·Ï‡ÙÂÚÔ˜ Â›Ó·È Ô ¯ÚfiÓÔ˜ ¤ÎıÂÛ˘ ÙÔ˘ ‚Ú¤ÊÔ˘˜ ÛÙÔÓ Î·Ófi. ¶·Ú¿ÁÔÓÙ·˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· SIDS ıˆÚÂ›Ù·È Î·È Ë ¯Ú‹ÛË Ô˘ÛÈÒÓ ·fi ÙË ÌËÙ¤Ú·, ΢ڛˆ˜ ÔÈÔÂȉÒÓ, ηıÒ˜ Î·È Ë ¯Ú‹ÛË ·ÏÎÔfiÏ, ȉ›ˆ˜ ÙÔ ÚÒÙÔ ÙÚ›ÌËÓÔ Ù˘ ÂÁ΢ÌÔÛ‡Ó˘. ∞ӷʤÚÂÙ·È Ì¿ÏÈÛÙ· fiÙÈ ·‰¤ÚÊÈ· ‚ÚÂÊÒÓ Ì ÂÌ‚Ú˘ÈÎfi ·ÏÎÔÔÏÈÎfi Û‡Ó‰ÚÔÌÔ ¤¯Ô˘Ó 10 ÊÔÚ¤˜ ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÁÈ· SIDS, Û˘ÁÎÚÈÓfiÌÂÓ· Ì ÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘ (1). ÕÏÏÔÈ ·Ú¿ÁÔÓÙ˜ ÁÈ· SIDS Ô˘ Û¯ÂÙ›˙ÔÓÙ·È Ì ÙË ÌËÙ¤Ú· Î·È ÙËÓ Î‡ËÛË Â›Ó·È Ë ¯·ÌËÏ‹ ÊÚÔÓÙ›‰· ÛÙËÓ ÂÁ΢ÌÔÛ‡ÓË, Ë Ôχ ÌÈÎÚ‹ ËÏÈΛ· Ù˘ ÌËÙ¤Ú·˜, ÙÔ ÌÈÎÚfi ‰È¿ÛÙËÌ· ·Ó¿ÌÂÛ· ÛÙȘ ÂÁ΢ÌÔÛ‡Ó˜, ÙÔ ¯·ÌËÏfi ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈÎfi Â›Â‰Ô Î·È ÙÔ ¯·ÌËÏfi Â›Â‰Ô ÌfiÚʈÛ˘ Ù˘ ÌËÙ¤Ú·˜. ∂›Û˘, ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ıˆÚÔ‡ÓÙ·È Ë ÔÈÎÔÁ¤ÓÂÈ· Ì ¤Ó· ÁÔÓÈfi, Ë ÂÓ‰ÔÌ‹ÙÚÈ· ˘ÔÍ›·, Ë ÂÓ‰ÔÌ‹ÙÚÈ· ηı˘ÛÙ¤ÚËÛË Ù˘ ·‡ÍËÛ˘, ÙÔ ¯·ÌËÏfi ‚¿ÚÔ˜ Á¤ÓÓËÛ˘, ÔÈ ÔÏÏ·Ϥ˜ ΢‹ÛÂȘ Î·È Ù· ÚfiˆÚ· ÓÂÔÁÓ¿. √ ÚÔËÁÔ‡ÌÂÓÔ˜ ı¿Ó·ÙÔ˜ ·fi SIDS ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ· Â›Ó·È ¤Ó·˜ ·ÎfiÌË ·Ú¿ÁÔÓÙ·˜ ÎÈÓ‰‡ÓÔ˘. øÛÙfiÛÔ, ·ÚfiÏÔ Ô˘ Ô Û¯ÂÙÈÎfi˜ ΛӉ˘ÓÔ˜ Â·Ó¿Ï˄˘ SIDS Û ÂfiÌÂÓÔ ·È‰› Â›Ó·È 5 ÊÔÚ¤˜ ÌÂÁ·Ï‡ÙÂÚÔ˜, ÔÈ ÁÔÓ›˜ Ú¤ÂÈ Ó· ‰È·‚‚·ÈÒÓÔÓÙ·È ÁÈ· ÙË ÛÔ˘‰·ÈfiÙËÙ· ÙˆÓ ÂÚÈ‚·ÏÏÔÓÙÈÎÒÓ ·Ú·ÁfiÓÙˆÓ (10).

Paediatriki 2008;71:304-310

¶·Ú¿ÁÔÓÙ˜ ÌÂÙ¿ ÙË Á¤ÓÓËÛË Ô˘ Úԉȷı¤ÙÔ˘Ó ÁÈ· SIDS ∏ ËÏÈΛ· ÙÔ˘ ‚Ú¤ÊÔ˘˜ Â›Ó·È ¤Ó·˜ ·fi ·˘ÙÔ‡˜, ·ÊÔ‡ Ô ÌÂÁ·Ï‡ÙÂÚÔ˜ ΛӉ˘ÓÔ˜ ÁÈ· SIDS Â›Ó·È Û ‚Ú¤ÊË ÌÂٷ͇ 2 Î·È 4 ÌËÓÒÓ Î·È ÔÈ ÂÚÈÛÛfiÙÂÚ˜ ÂÚÈÙÒÛÂȘ ı·Ó¿ÙˆÓ SIDS Û˘Ì‚·›ÓÔ˘Ó ÚÈÓ ·fi ÙÔ˘˜ 6 Ì‹Ó˜ ˙ˆ‹˜. ÕÏÏÔ˜ ·Ú¿ÁÔÓÙ·˜ ÎÈÓ‰‡ÓÔ˘ Â›Ó·È ÙÔ Ê‡ÏÔ: Û¯¤ÛË ·ÁfiÚÈ·/ÎÔÚ›ÙÛÈ· 3:2 (4). ∏ ·ÏÏ·Á‹ Ù˘ ı¤Û˘ ÛÙÔÓ ‡ÓÔ ·fi ÚËÓ‹ Û ‡ÙÈ· ÙȘ ÙÂÏÂ˘Ù·›Â˜ 2 ‰ÂηÂٛ˜ ÂÏ¿ÙÙˆÛ ηٿ 50% ÙË Û˘¯ÓfiÙËÙ· ÙÔ˘ SIDS (11). £ÂˆÚÂ›Ù·È fiÙÈ Ô Ì˯·ÓÈÛÌfi˜, Ì ÙÔÓ ÔÔ›Ô Ë ‡ÙÈ· ı¤ÛË ÚÔÛٷهÂÈ, Û¯ÂÙ›˙ÂÙ·È Ì ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ·˘Í¿ÓÂÈ ÙË ‰˘Ó·ÙfiÙËÙ· ·Ê‡ÓÈÛ˘ ÙˆÓ ‚ÚÂÊÒÓ Î·È ÛÙȘ ‰‡Ô Ê¿ÛÂȘ ÙÔ˘ ‡ÓÔ˘ οÓÔÓÙ¿˜ Ù· ÏÈÁfiÙÂÚÔ Â˘ÚfiÛ‚ÏËÙ· ÛÙÔ SIDS (11). ∏ ı¤ÛË ‡ÓÔ˘ ÛÙÔ Ï¿È ıˆÚÂ›Ù·È ÂÈÛÊ·Ï‹˜, ÁÈ·Ù› Ù· ‚Ú¤ÊË Â˘ÎÔÏfiÙÂÚ· Á˘Ú›˙Ô˘Ó ·fi ÙËÓ Ï¿ÁÈ· ı¤ÛË ÛÙËÓ ÚËÓ‹ ·’ fi,ÙÈ ·fi ÙËÓ ‡ÙÈ· Û ÚËÓ‹ (10). ¢ÂÓ ·Ú·ÁÓˆÚ›˙ÂÙ·È ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ë ‡ÙÈ· ı¤ÛË ÛÙÔÓ ‡ÓÔ Û˘Óԉ‡ÂÙ·È Ì ·˘ÍË̤ÓË Û˘¯ÓfiÙËÙ· Á·ÛÙÚÔÔÈÛÔÊ·ÁÈ΋˜ ·ÏÈÓ‰ÚfiÌËÛ˘, ÂÈÛÚfiÊËÛ˘, Ï·ÁÈÔÎÂÊ·Ï›·˜ Î·È Î·ı˘ÛÙÂÚË̤Ó˘ ηٿÎÙËÛ˘ ÙˆÓ ÎÈÓËÙÈÎÒÓ ‰ÂÍÈÔًوÓ. Œ¯ÂÈ ·Ô‰Âȯı› fï˜ fiÙÈ ÔÈ ÂÈÏÔΤ˜ ·˘Ù¤˜ Â›Ó·È Â‡ÎÔÏ· ·ÓÙÈÌÂÙˆ›ÛÈ̘ Î·È ÂÏ¿ÛÛÔÓÔ˜ ÛËÌ·Û›·˜ ÌÚÔÛÙ¿ ÛÙÔ ÙÚ·ÁÈÎfi ÁÂÁÔÓfi˜ ÙÔ˘ SIDS (3). ™˘ÁÎÂÎÚÈ̤ӷ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ Ï·ÁÈÔÎÂÊ·Ï›·˜, Ù˘ ÔÔ›·˜ Ë Û˘¯ÓfiÙËÙ· ·˘Í‹ıËΠ̠ÙËÓ Î·ıȤڈÛË Ù˘ ‡ÙÈ·˜ ı¤Û˘ ÛÙÔÓ ‡ÓÔ, Û˘ÓÈÛÙ¿Ù·È Ó· ÙÔÔıÂÙÂ›Ù·È ÙÔ ‚Ú¤ÊÔ˜ Û ¿ÏϘ ı¤ÛÂȘ, fiÙ·Ó Â›Ó·È Í‡ÓÈÔ. ∆· ÂÚÈÛÛfiÙÂÚ· ‚Ú¤ÊË Ô˘ ·ÎÔÏÔ˘ıÔ‡Ó ÙȘ Ô‰ËÁ›Â˜ ·˘Ù¤˜ ‚ÂÏÙÈÒÓÔÓÙ·È Û ‰È¿ÛÙËÌ· 2-3 ÌËÓÒÓ (13). ªÈ· ÎÔÈÓ‹ Ú·ÎÙÈ΋ ÁÈ· ÔÏϤ˜ ÔÈÎÔÁ¤ÓÂȘ Â›Ó·È ÙÔ ÌÔ›Ú·ÛÌ· ÙÔ˘ ÎÚ‚·ÙÈÔ‡ Ì ÙÔ ‚Ú¤ÊÔ˜. ™Â ÌÈ· ÌÂϤÙË ·Ó·Ê¤ÚÂÙ·È fiÙÈ 20,5% ÙˆÓ ‚ÚÂÊÒÓ ÌÔÈÚ¿˙ÔÓÙ·È ¿ÓÙ· ÙÔ ÎÚ‚¿ÙÈ ÙÔ˘˜ Ì ÙÔ˘˜ ÁÔÓ›˜, 14,7% ÙˆÓ ‚ÚÂÊÒÓ Û¯Â‰fiÓ ¿ÓÙ·, 41,5% ÌÂÚÈΤ˜ ÊÔÚ¤˜ Î·È 23,4% ÔÙ¤ (2). ™Â ¿ÏÏË ÌÂϤÙË ‚Ú¤ıËΠfiÙÈ ÙÔ 47% ÙˆÓ ‚ÚÂÊÒÓ ¤¯Ô˘Ó ÌÔÈÚ·ÛÙ› ÙÔ ÎÚ‚¿ÙÈ Ì ÙÔ˘˜ ÁÔÓ›˜ ÙÔ˘Ï¿¯ÈÛÙÔÓ Ì›· ÊÔÚ¿ ÁÈ· Ï›Á˜ ÒÚ˜ ‹ ÔÏfiÎÏËÚË ÙË Ó‡¯Ù· (14). ÕÏϘ ÌÂϤÙ˜ ¤¯Ô˘Ó Û˘Û¯ÂÙ›ÛÂÈ ÙÔ ÌÔ›Ú·ÛÌ· ÙÔ˘ ÎÚ‚·ÙÈÔ‡ Ì ¯·ÌËÏfi ÎÔÈÓˆÓÈÎÔÔÈÎÔÓÔÌÈÎfi Â›‰Ô, Ì ÌÔÓÔÁÔÓÂ˚Τ˜ ‹ ÔÏ˘ÌÂÏ›˜ ÔÈÎÔÁ¤ÓÂȘ, Ì ÙÔ˘˜ ¯ÂÈÌÂÚÈÓÔ‡˜ Ì‹Ó˜ Î·È Ù· ™·‚‚·ÙÔ·Úȷη. ∆· ‰Â‰Ô̤ӷ Ô˘ ˘¿Ú¯Ô˘Ó Û‹ÌÂÚ· Â›Ó·È ·ÓÂ·Ú΋ ÁÈ· Ó· ˘ÔÛÙËÚȯÙ› fiÙÈ ÙÔ ÎÔÈÓfi ÎÚ‚¿ÙÈ Ì ÙÔ˘˜ ÁÔÓ›˜, οو ·fi ÚÔÛÂÎÙÈο ÂÈÏÂÁ̤Ó˜ Û˘Óı‹Î˜, Â›Ó·È ÍÂοı·Ú· ÂÈ‚Ï·‚¤˜ ‹ ·ÛʷϤ˜ (3). ∆· ÏÂÔÓÂÎÙ‹Ì·Ù· Â›Ó·È fiÙÈ ·˘Í¿ÓÂÈ ÙËÓ ·ÓÙ›ÏË„Ë ÙˆÓ ÁÔÓÈÒÓ ÁÈ· ÙȘ ·Ó¿ÁΘ ÙÔ˘ ‚Ú¤ÊÔ˘˜ ÙÔ˘˜ Î·È Î¿ÓÂÈ ÏÈÁfiÙÂÚÔ ‚·ı‡ ÙÔÓ ‡ÓÔ ÙˆÓ ‚ÚÂÊÒÓ (3). ∂›Û˘, ÚÔ¿ÁÂÈ ÙÔ ÌËÙÚÈÎfi ıËÏ·ÛÌfi. √È ÌÂÏÂÙËÙ¤˜ ηٷϋÁÔ˘Ó fiÙÈ Ù· ‚Ú¤ÊË Ô˘ ÌÔÈÚ¿˙ÔÓÙ·È

Pediatri Jul-Aug 08

30-07-08

15:53

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™‡Ó‰ÚÔÌÔ ·ÈÊÓ›‰ÈÔ˘ ‚ÚÂÊÈÎÔ‡ ı·Ó¿ÙÔ˘

ÙÔ ÎÚ‚¿ÙÈ Ì ÙÔ˘˜ ÁÔÓ›˜ Â›Ó·È Û ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÁÈ· SIDS, fiÙ·Ó ÔÈ ÁÔÓ›˜ Â›Ó·È Î·ÓÈÛÙ¤˜, ·¯‡Û·ÚÎÔÈ, ¯Ú‹ÛÙ˜ ·ÏÎÔfiÏ ‹ ηٷÛÙ·ÏÙÈÎÒÓ Ê·ÚÌ¿ÎˆÓ ‹ Â›Ó·È ÂÍ·ÈÚÂÙÈο ÎÔ˘Ú·Ṳ̂ÓÔÈ. √ ΛӉ˘ÓÔ˜ Ì¿ÏÈÛÙ· ·˘Í¿ÓÂÈ ÁÈ· Ù· ¯·ÌËÏÔ‡ ‚¿ÚÔ˘˜ ÁÈ· ÙËÓ ËÏÈΛ· ·ËÛ˘ ‚Ú¤ÊË, ηıÒ˜ Î·È ÁÈ’ ·˘Ù¿ Ô˘ Â›Ó·È ÌÈÎÚfiÙÂÚ· ÙˆÓ 8-11 ‚‰ÔÌ¿‰ˆÓ. ∆· ÌÂÁ·Ï‡ÙÂÚ· ÙˆÓ 20 ‚‰ÔÌ¿‰ˆÓ ‚Ú¤ÊË ‰ÂÓ Ù›ıÂÓÙ·È Û ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ ÁÈ· SIDS ·fi ÙÔ ÌÔ›Ú·ÛÌ· ÙÔ˘ ÎÚ‚·ÙÈÔ‡. µÚ¤ÊË Ô˘ ÎÔÈÌÔ‡ÓÙ·È ·Ó¿ÌÂÛ· Û ‰‡Ô ÂÓ‹ÏÈΘ Â›Ó·È Û ÌÂÁ·Ï‡ÙÂÚÔ Î›Ó‰˘ÓÔ ·fi ·˘Ù¿ Ô˘ ÎÔÈÌÔ‡ÓÙ·È ‰›Ï· Û ¤Ó·Ó (15). ∆Ô ÌÂÁ·Ï‡ÙÂÚÔ ıÂÚÌÈÎfi ÛÙÚ˜, ÛÙÔ ÔÔ›Ô ÂÎÙ›ıÂÓÙ·È, Î·È Ë ÌÂÁ·Ï‡ÙÂÚË Èı·ÓfiÙËÙ· Î¿Ï˘„˘ Ù˘ ÎÂÊ·Ï‹˜, ıˆÚÔ‡ÓÙ·È ÔÈ ÈÔ Èı·ÓÔ› Ì˯·ÓÈÛÌÔ› Ô˘ ¢ÓÔÔ‡Ó ÙÔ SIDS ÛÙ· ‚Ú¤ÊË Ô˘ ÎÔÈÌÔ‡ÓÙ·È Ì ÙÔ˘˜ ÁÔÓ›˜ ÙÔ˘˜ (15). ∏ ˘ÂÚı¤ÚÌ·ÓÛË ÙÔ˘ ¯ÒÚÔ˘ Ú¤ÂÈ Ó· ·ÔʇÁÂÙ·È.

SIDS Î·È ıËÏ·ÛÌfi˜ ∂›Ó·È ÎÔÈÓ‹ ·Ú·Ù‹ÚËÛË fiÙÈ Ù· ‚Ú¤ÊË Ô˘ ¤ı·Ó·Ó ·fi Û‡Ó‰ÚÔÌÔ ·ÈÊÓ›‰ÈÔ˘ ‚ÚÂÊÈÎÔ‡ ı·Ó¿ÙÔ˘ ÛÈÙ›˙ÔÓÙ·È Ì ÌÈÌÂÚfi Û˘¯ÓfiÙÂÚ· ·’ fi,ÙÈ Ù· ‚Ú¤ÊË ÛÙȘ ÔÌ¿‰Â˜ ÂϤÁ¯Ô˘. ∂›Ó·È ˆÛÙfiÛÔ ·ÌÊÈÏÂÁfiÌÂÓÔ ·Ó Ë Û›ÙÈÛË Ì ÌÈÌÂÚfi ·ÔÙÂÏ› ·ÓÂÍ¿ÚÙËÙÔ ·Ú¿ÁÔÓÙ· ÎÈÓ‰‡ÓÔ˘. √ÚÈṲ̂ÓÔÈ ÂÚ¢ÓËÙ¤˜ ‰¤¯ÔÓÙ·È fiÙÈ ÛÙ· ÁÂÓÈÎfiÙÂÚ· ¢ÂÚÁÂÙÈο ·ÔÙÂϤÛÌ·Ù· ÙÔ˘ ÌËÙÚÈÎÔ‡ ıËÏ·ÛÌÔ‡ ÔÊ›ÏÂÙ·È ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ù· ‚Ú¤ÊË Ô˘ ıËÏ¿˙Ô˘Ó ÁÈ· Ì·ÎÚ‡ÙÂÚË ÂÚ›Ô‰Ô ¤¯Ô˘Ó ÌÈÎÚfiÙÂÚÔ Î›Ó‰˘ÓÔ ÌÂÙ·ÓÂÔÁÓÈÎÔ‡ ı·Ó¿ÙÔ˘ (12,16). ÕÏÏÔÈ ˘ÔÛÙËÚ›˙Ô˘Ó ÙËÓ ¿ÌÂÛË ÚÔÛٷ٢ÙÈ΋ ‰Ú¿ÛË ÙÔ˘ ÌËÙÚÈÎÔ‡ ıËÏ·ÛÌÔ‡ ÛÙÔ SIDS, ̤ۈ Ù˘ Ì›ˆÛ˘ ÙÔ˘ Ô˘‰Ô‡ ·Ê‡ÓÈÛ˘ ÛÙ· ıËÏ¿˙ÔÓÙ· ‚Ú¤ÊË (1). ¶ÚÔÙÂÈÓfiÌÂÓÔÈ, Â›Û˘, Ì˯·ÓÈÛÌÔ› Ù˘ ¢ÂÚÁÂÙÈ΋˜ Â›‰Ú·Û˘ ÙÔ˘ ÌËÙÚÈÎÔ‡ ıËÏ·ÛÌÔ‡ ÛÙÔ SIDS Â›Ó·È Ë Û˘¯ÓfiÙÂÚË Û›ÙÈÛË ÙˆÓ ıËÏ·˙fiÓÙˆÓ ‚ÚÂÊÒÓ, Ë ÛÙÂÓfiÙÂÚË Â·Ê‹ Ì ÙË ÌËÙ¤Ú· Î·È Ë ¯·ÌËÏfiÙÂÚË Û˘¯ÓfiÙËÙ· ÏÔÈÌÒÍÂˆÓ Û’ ·˘Ù¿. ÃÚ‹ÛË È›Ï·˜ Î·È SIDS ªÂ ÙÔÓ ›‰ÈÔ Ì˯·ÓÈÛÌfi, ‰ËÏ·‰‹ ÙË Ì›ˆÛË ÙÔ˘ Ô˘‰Ô‡ ·Ê‡ÓÈÛ˘, ÈÛÙ‡ÂÙ·È fiÙÈ ‰Ú· ÚÔÛٷ٢ÙÈο Î·È Ë ¯Ú‹ÛË È›Ï·˜ ÛÙÔ SIDS. À¿Ú¯Ô˘Ó ‚¤‚·È· ÚÔ‚Ï‹Ì·Ù· ·fi ÙË ¯Ú‹ÛË Ù˘, fiˆ˜ fiÙÈ ÂÌÔ‰›˙ÂÈ ÙÔ ÌËÙÚÈÎfi ıËÏ·ÛÌfi, ·˘Í¿ÓÂÈ ÙË Û˘¯ÓfiÙËÙ· ÏÔÈÌÒÍÂˆÓ ÙÔ˘ ·˘ÙÈÔ‡ Î·È ·˘Í¿ÓÂÈ Ù· ÔÚıÔ‰ÔÓÙÈο ÚÔ‚Ï‹Ì·Ù·. £ÂˆÚÂ›Ù·È fï˜ fiÙÈ Ë ¯ÚËÛÈÌÔÔ›ËÛ‹ Ù˘ ÌÂÙ¿ ÙËÓ 4Ë Â‚‰ÔÌ¿‰· Ù˘ ˙ˆ‹˜ Î·È ÙËÓ Â‰Ú·›ˆÛË ÙÔ˘ ÌËÙÚÈÎÔ‡ ıËÏ·ÛÌÔ‡ ÌÔÚ› Ó· Û˘ÓÂÈÛʤÚÂÈ ıÂÙÈο ÛÙËÓ ÚfiÏË„Ë ÙÔ˘ SIDS (12). ∂Ì‚fiÏÈ· Î·È SIDS ∫·Ì›· Û˘Û¯¤ÙÈÛË ‰ÂÓ ¤¯ÂÈ ‚ÚÂı› ÌÂٷ͇ ÂÌ‚ÔÏ›ˆÓ Î·È SIDS (1).

§ÔÈÌÒÍÂȘ Î·È SIDS ¶ÚfiÛÊ·ÙË ÂÌ‡ÚÂÙË Ïԛ̈ÍË Ù˘ ·ÓÒÙÂÚ˘ ·Ó·Ó¢ÛÙÈ΋˜ Ô‰Ô‡ ‚Ú›ÛÎÂÙ·È ÛÙÔ 50% ÙˆÓ ÂÚÈÙÒÛÂˆÓ SIDS, ·ÏÏ¿ Ë Ïԛ̈ÍË ıˆÚÂ›Ù·È ÂÈ‚·Ú˘ÓÙÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ ÌfiÓÔ Û ÁÂÓÂÙÈο ÚԉȷÙÂıÂÈ̤ӷ ¿ÙÔÌ·. Œ¯ÂÈ ·Ú·ÙËÚËı› fiÙÈ Ù· ı‡Ì·Ù· SIDS ¤¯Ô˘Ó Û˘Ó‹ıˆ˜ Ì·ÎÚ‡ÙÂÚÔ ÈÛÙÔÚÈÎfi ·fi ÓfiÛÔ˘˜ Î·È Û˘¯ÓfiÙÂÚ˜ ÂÈÛ·ÁˆÁ¤˜ ÛÙÔ ÓÔÛÔÎÔÌÂ›Ô Û˘ÁÎÚÈÓfiÌÂÓ· Ì ÙËÓ ÔÌ¿‰· ÂϤÁ¯Ô˘ (6). ∞ÂÈÏËÙÈο ÁÈ· ÙË ˙ˆ‹ ÂÂÈÛfi‰È· (Apparent Life Threatening Events - ALTE) ∏ Û¯¤ÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ·ÈÊÓ›‰ÈÔ˘ ı·Ó¿ÙÔ˘ Ì ٷ ALTE ‰ÂÓ ¤¯ÂÈ ‰È¢ÎÚÈÓÈÛÙ›. ø˜ ALTE ÔÚ›˙ÔÓÙ·È ÂÂÈÛfi‰È· Ô˘ ÙÚÔÌ¿˙Ô˘Ó ÙÔÓ ·Ú·ÙËÚËÙ‹ Î·È ¯·Ú·ÎÙËÚ›˙ÔÓÙ·È ·fi οÔÈÔ Û˘Ó‰˘·ÛÌfi ¿ÓÔÈ·˜, ·ÏÏ·Á‹˜ ÙÔ˘ ¯ÚÒÌ·ÙÔ˜ (Û˘Ó‹ıˆ˜ ΢¿ÓˆÛË ‹ ˆ¯ÚfiÙËÙ·), ·ÍÈÔÛËÌ›ˆÙ˘ ·ÏÏ·Á‹˜ ÙÔ˘ Ì˘˚ÎÔ‡ ÙfiÓÔ˘ Î·È Â̤ÙÔ˘ ‹ ÚÔÛ¿ıÂÈ·˜ ÁÈ· ¤ÌÂÙÔ (17). ¶ÔÏÏÔ› ÌÂÏÂÙËÙ¤˜ ÈÛÙÂ‡Ô˘Ó fiÙÈ ˘¿Ú¯ÂÈ ÌÈÎÚ‹ ÌfiÓÔ ÂÈÎ¿Ï˘„Ë ·Ó¿ÌÂÛ· ÛÙÔ˘˜ ‰‡Ô ÏËı˘ÛÌÔ‡˜ (18). ¶Ú¿ÁÌ·ÙÈ, ÔÈ ·ÚÂÌ‚¿ÛÂȘ Ô˘ ÂÏ¿ÙÙˆÛ·Ó Ù· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ÙË Û˘¯ÓfiÙËÙ· ÙÔ˘ SIDS ‰ÂÓ Î·ÙfiÚıˆÛ·Ó Ó· ÌÂÈÒÛÔ˘Ó ÙË Û˘¯ÓfiÙËÙ· ÙˆÓ ∞L∆∂. ∏ Â›ÙˆÛË ÙˆÓ ALTE ÊÙ¿ÓÂÈ Ù· 0,62,4/1.000 ˙ÒÓÙ· ÓÂÔÁÓ¿ (17,19). ∂›Û˘, ·Ó Î·È ALTE Î·È SIDS Â›Ó·È ‰È·Ù·Ú·¯¤˜ Ô˘ ÂÌÊ·Ó›˙ÔÓÙ·È ÙÔÓ ÚÒÙÔ ¯ÚfiÓÔ ˙ˆ‹˜, ˆÛÙfiÛÔ Ë Ì¤ÛË ËÏÈΛ· Ô˘ Û˘Ì‚·›ÓÔ˘Ó Ù· ALTE Â›Ó·È Û˘Ó‹ıˆ˜ ÔÈ 8 ‚‰ÔÌ¿‰Â˜ (20). ª›· ÛËÌ·ÓÙÈ΋ ‰È·ÊÔÚ¿ Û¯ÂÙ›˙ÂÙ·È Ì ÙÔ ÁÂÁÔÓfi˜ fiÙÈ Ù· ALTE Û˘Ì‚·›ÓÔ˘Ó Û˘¯ÓfiÙÂÚ· fiÙ·Ó ÙÔ ‚Ú¤ÊÔ˜ Â›Ó·È Í‡ÓÈÔ, ÂÓÒ Ô ·ÈÊÓ›‰ÈÔ˜ ‚ÚÂÊÈÎfi˜ ı¿Ó·ÙÔ˜ Û˘Ì‚·›ÓÂÈ Û˘Ó‹ıˆ˜ ηٿ ÙË ‰È¿ÚÎÂÈ· ÙÔ˘ ‡ÓÔ˘ (17). ÕÏÏÔÈ ¿ÏÈ ÂÚ¢ÓËÙ¤˜ ˘ÔÛÙËÚ›˙Ô˘Ó fiÙÈ ÚfiÎÂÈÙ·È ÁÈ· ‰È·ÊÔÚÂÙÈΤ˜ ÂÎÊÚ¿ÛÂȘ Ù˘ ›‰È·˜ ÓfiÛÔ˘, ηıÒ˜ 12% ÙˆÓ ı˘Ì¿ÙˆÓ SIDS ›¯·Ó ÚÔËÁÔ‡ÌÂÓË ÂÌÂÈÚ›· ÂÓfi˜ ‹ ÂÚÈÛÛfiÙÂÚˆÓ ÂÂÈÛÔ‰›ˆÓ ALTE. ⁄ÛÙÂÚ· ·fi ¤Ó· ÂÂÈÛfi‰ÈÔ ALTE, Ô Î›Ó‰˘ÓÔ˜ ÁÈ· SIDS ·˘Í¿ÓÂÈ ÂÚÈÛÛfiÙÂÚÔ, fiÙ·Ó ÙÔ ALTE Û˘Û¯ÂÙ›˙ÂÙ·È Ì Û·ÛÌÔ‡˜ ‹ ηډȷ΋ ·ÚÚ˘ıÌ›· (19). ÕÓÔÈ· Î·È SIDS ∂›Ó·È ÌÈ· Û¯¤ÛË Ô˘ ‰ÈÂÚÂ˘Ó¿Ù·È ÂÓ‰ÂϯҘ ÛÙË ‚È‚ÏÈÔÁÚ·Ê›·. ø˜ ¿ÓÔȘ ÔÚ›˙ÔÓÙ·È ·ÓÂÍ‹ÁËÙ· ÂÂÈÛfi‰È· Ì ÛÙ·Ì¿ÙËÌ· Ù˘ ·Ó·ÓÔ‹˜ ‰È¿ÚÎÂÈ·˜ 20 ‰Â˘ÙÂÚÔϤÙˆÓ ‹ ÂÚÈÛÛfiÙÂÚÔ ‹ ‚Ú·¯‡ÙÂÚÔ ‰È¿ÛÙËÌ· ·Ó·Ó¢ÛÙÈ΋˜ ·‡Û˘ Ô˘ Û˘Óԉ‡ÂÙ·È ·fi ‚Ú·‰˘Î·Ú‰›·, ΢¿ÓˆÛË ‹ ˆ¯ÚfiÙËÙ· ‹ ÂÎÛÂÛËÌ·Ṳ̂ÓË ˘ÔÙÔÓ›· Û ÓÂÔÁÓfi Ì ËÏÈΛ· ·ËÛ˘ ÌÂÁ·Ï‡ÙÂÚË ÙˆÓ 37 ‚‰ÔÌ¿‰ˆÓ (21). ¶·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ¿ÓÔÈ· Â›Ó·È Î˘Ú›ˆ˜ ÙÔ Î¿ÓÈÛÌ· Ù˘ ÌËÙ¤Ú·˜, Ô ÚfiˆÚÔ˜ ÙÔÎÂÙfi˜, ÙÔ ¯·ÌËÏfi ‚¿ÚÔ˜ ¶·È‰È·ÙÚÈ΋ 2008;71:304-310

Pediatri Jul-Aug 08

30-07-08

15:53

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308

™. ™ÙÂÊ·Ó¿ÎË, ∞. ∆ÛÈÏÈÌÈÁοÎË

Á¤ÓÓËÛ˘, Ë ÂÈÛ·ÁˆÁ‹ Û ÌÔÓ¿‰· ÓÂÔÁÓÒÓ, ÔÈ Û·ÛÌÔ›, ÙÔ Ù¿ÈÛÌ· Ì ÌÈÌÂÚfi Î·È ÔÈ ‰˘ÛÎÔϛ˜ ÛÙË Û›ÙÈÛË (19). ∏ Û¯¤ÛË ·ÓÔÈÒÓ Î·È SIDS ‰ÂÓ Â›Ó·È ÍÂοı·ÚË. ∞Ó Î·È Ë ¿ÓÔÈ· ıˆÚÂ›Ù·È ·fi ÔÏÏÔ‡˜ Èı·Ófi˜ Ì˯·ÓÈÛÌfi˜ SIDS, ˆÛÙfiÛÔ Ë Û˘¯ÓfiÙËÙ· ÙˆÓ ·ÓÔÈÒÓ (5,3%) Â›Ó·È Ôχ ÌÂÁ·Ï‡ÙÂÚË ·fi ÙË Û˘¯ÓfiÙËÙ· ÙÔ˘ SIDS (19). Œ¯ÂÈ ‚ÚÂı› fiÙÈ Û ÔÈÎÔÁ¤ÓÂȘ Ô˘ ̤ÏË ÙÔ˘˜ ›¯·Ó ÂÂÈÛfi‰È· ·ÔÊÚ·ÎÙÈ΋˜ ¿ÓÔÈ·˜ Ô ·ÈÊÓ›‰ÈÔ˜ ‚ÚÂÊÈÎfi˜ ı¿Ó·ÙÔ˜ ‹Ù·Ó 24 ÊÔÚ¤˜ Û˘¯ÓfiÙÂÚÔ˜ (22). ™˘Û΢¤˜ ·Ú·ÎÔÏÔ‡ıËÛ˘ ηډÈÔ·Ó·Ó¢ÛÙÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ ∏ ¯Ú‹ÛË ÙˆÓ Û˘Û΢ÒÓ ·˘ÙÒÓ ÍÂΛÓËÛ ·fi ÙÔ 1970 (20). ™‹ÌÂÚ· ÈÛÙ‡ÂÙ·È fiÙÈ Ë ¯Ú‹ÛË ÙÔ˘˜ Ú¤ÂÈ Ó· ·ÔʇÁÂÙ·È, ÁÈ·Ù› ÚÔηÏ› ÔÏϤ˜ ÊÔÚ¤˜ ÎÈÓËÙÔÔ›ËÛË ÙˆÓ ÁÔÓÈÒÓ ¯ˆÚ›˜ ÏfiÁÔ, ÁÂÁÔÓfi˜ Ô˘ ÙÔ˘˜ ÚÔηÏ› ¿Á¯Ô˜ Î·È Û˘¯Ó¿ ÔÈ ÁÔÓ›˜ ¤¯Ô˘Ó ·ÓÂ·Ú΋ ÂÎ·›‰Â˘ÛË ÙfiÛÔ ÛÙË ¯ÚËÛÈÌÔÔ›ËÛ‹ ÙÔ˘˜, fiÛÔ Î·È ÛÙȘ Ú·ÎÙÈΤ˜ Ù˘ ηډÈÔ·Ó·Ó¢ÛÙÈ΋˜ ·Ó·˙ˆÔÁfiÓËÛ˘. ÕÏψÛÙÂ, ‰ÂÓ ˘¿Ú¯Ô˘Ó Â·Ú΋ ‰Â‰Ô̤ӷ ÁÈ· ÙË Ì›ˆÛË ÙÔ˘ SIDS ÌÂÙ¿ ÙË ¯Ú‹ÛË ÙÔ˘˜ (23). ™‹ÌÂÚ·, Ë ¯ÚËÛÈÌÔÔ›ËÛË ÙˆÓ Û˘Û΢ÒÓ ·˘ÙÒÓ Û˘˙ËÙÂ›Ù·È Û ÛÔ‚·Úfi ȉÈÔ·ı¤˜ ALTE Ô˘ ··›ÙËÛ ·Ó·Ó¢ÛÙÈ΋ ·Ó·˙ˆÔÁfiÓËÛË, Û ‰‡Ô ‹ ÂÚÈÛÛfiÙÂÚÔ˘˜ ·ÈÊÓ›‰ÈÔ˘˜ ‚ÚÂÊÈÎÔ‡˜ ı·Ó¿ÙÔ˘˜ ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ·, ÛÂ Û˘Ìو̷ÙÈο ÚfiˆÚ· ‚Ú¤ÊË Î·È ÛÂ Û˘Ìو̷ÙÈο ‚Ú¤ÊË Ì ¯ÚfiÓÈ· ÓÔÛ‹Ì·Ù· (26). ¶ÚÔÙÈÌÒÓÙ·È ÔÈ Û˘Û΢¤˜ ·Ú·ÎÔÏÔ‡ıËÛ˘ ηډÈÔ·Ó·Ó¢ÛÙÈ΋˜ ÏÂÈÙÔ˘ÚÁ›·˜ Î·È ‰È·ÎfiÙÂÙ·È Ë ¯Ú‹ÛË ÙÔ˘˜ fiÙ·Ó ÙÔ ‚Ú¤ÊÔ˜ Â›Ó·È ·Û˘Ìو̷ÙÈÎfi ÁÈ· 6 ‚‰ÔÌ¿‰Â˜ ‹ ¤¯ÂÈ Û˘ÌÏËÚÒÛÂÈ ÙÔÓ 6Ô Ì‹Ó· Ù˘ ˙ˆ‹˜ ÙÔ˘ (19). ∫·ÎÔÔ›ËÛË – ÂÁÎÏËÌ·ÙÈ΋ ÂÓ¤ÚÁÂÈ· Î·È SIDS √ ·È‰›·ÙÚÔ˜ Ô˘ ‚Ú›ÛÎÂÙ·È ·ÓÙÈ̤وÔ˜ Ì’ ¤Ó·Ó ·ÈÊÓ›‰ÈÔ ı¿Ó·ÙÔ ‚Ú¤ÊÔ˘˜ Ú¤ÂÈ Ó· ÛΤÊÙÂÙ·È Î·È ÙÔ ÂӉ¯fiÌÂÓÔ Ù˘ ηÎÔÔ›ËÛ˘ ‹ Ù˘ ÂÁÎÏËÌ·ÙÈ΋˜ ÂÓ¤ÚÁÂÈ·˜, ηıÒ˜ Ù· ‚Ú¤ÊË Â›Ó·È ÂÚÈÛÛfiÙÂÚÔ Â˘ÚfiÛ‚ÏËÙ· Û ηÎÔÔ›ËÛË ·fi ÔÔÈ·‰‹ÔÙ ¿ÏÏË ËÏÈÎȷ΋ ÔÌ¿‰· (23). ∏ ηÎÔÔ›ËÛË/ÂÁÎÏËÌ·ÙÈ΋ ÂÓ¤ÚÁÂÈ· ·ÊÔÚ¿ ÙÔ 10% ÙˆÓ Í·ÊÓÈÎÒÓ ·ÓÂÍ‹ÁËÙˆÓ ı·Ó¿ÙˆÓ ÙˆÓ ‚ÚÂÊÒÓ (31). ∆ËÓ ˘ÔÙ¢fiÌ·ÛÙ fiÙ·Ó Ô ı¿Ó·ÙÔ˜ ÙÔ˘ ‚Ú¤ÊÔ˘˜ Û˘Ì‚·›ÓÂÈ Û ËÏÈΛ· ÌÂÁ·Ï‡ÙÂÚË ÙˆÓ 6 ‹ ·ÎfiÌ· ÂÚÈÛÛfiÙÂÚÔ ÙˆÓ 12 ÌËÓÒÓ ‹ fiÙ·Ó Û˘Ì‚·›ÓÂÈ ÍËÌÂÚÒÌ·Ù· ‹ ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ Ë̤ڷ˜. ⁄ÔÙ˜ Â›Ó·È ÔÈ ÂÚÈÙÒÛÂȘ fiÙ·Ó ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ· ˘¿Ú¯Ô˘Ó ÁÔÓ›˜, Î·È ÂȉÈο ÌËÙ¤Ú˜, Ì ηٿıÏÈ„Ë, ‰È·Ù·Ú·¯¤˜ ÚÔÛˆÈÎfiÙËÙ·˜, ¯ÚfiÓÈ· ۈ̷ÙÈο ‹ „˘¯È·ÙÚÈο ÓÔÛ‹Ì·Ù· (24). √ ÚÔËÁÔ‡ÌÂÓÔ˜ ·ÓÂÍ‹ÁËÙÔ˜ ı¿Ó·ÙÔ˜ ÂÓfi˜ ‚Ú¤ÊÔ˘˜ ÛÙËÓ ÔÈÎÔÁ¤ÓÂÈ· Â›Ó·È ¤Ó·˜ ·Ú¿ÁÔÓÙ·˜ Paediatriki 2008;71:304-310

¶›Ó·Î·˜ 3. ∫·Ù¢ı˘ÓÙ‹ÚȘ √‰ËÁ›Â˜ ÁÈ· ÚfiÏË„Ë SIDS Ù˘ ∞ÌÂÚÈηÓÈ΋˜ ∞η‰ËÌ›·˜ ¶·È‰È·ÙÚÈ΋˜ (12,26) 1. ∆Ô ‚Ú¤ÊÔ˜ Ú¤ÂÈ Ó· ÎÔÈÌ¿Ù·È Û ‡ÙÈ· ı¤ÛË. ∏ ı¤ÛË ‡ÓÔ˘ ÛÙÔ Ï¿È ‰ÂÓ Â›Ó·È ·ÛÊ·Ï‹˜ Î·È ‰ÂÓ Ú¤ÂÈ Ó· Û˘ÓÈÛٿٷÈ.

2. √ ‡ÓÔ˜ ÙÔ˘ ‚Ú¤ÊÔ˘˜ Ó· Â›Ó·È Û ÛÙ·ıÂÚ‹ ÂÈÊ¿ÓÂÈ·. ∆Ô ÛÙÚÒÌ· Ú¤ÂÈ Ó· Â›Ó·È Û¯ÂÙÈο ÛÎÏËÚfi Î·È Ó· ηχÙÂÙ·È ·fi ÛÂÓÙfiÓÈ.

3. ™ÙËÓ ÎÔ‡ÓÈ· ÙÔ˘ ‚Ú¤ÊÔ˘˜ ‰ÂÓ Ú¤ÂÈ Ó· ˘¿Ú¯Ô˘Ó ̷Ϸο ·ÓÙÈΛÌÂÓ·, Ì·ÍÈÏ¿ÚÈ· ‹ ¯ÓÔ˘‰ˆÙ¿ ·È¯Ó›‰È·. ¡· ·ÔʇÁÔÓÙ·È ÎÔ˘‚¤ÚÙ˜ ‹ ·ÏÒÌ·Ù· Î·È fiÙ·Ó ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È Ó· ·ÛÊ·Ï›˙ÔÓÙ·È ÛÙ· Ï¿ÁÈ· Ù˘ ÎÔ‡ÓÈ·˜, ÁÈ· Ó· ÌË ÌÔÚ› ÙÔ ‚Ú¤ÊÔ˜ Ó· ηχ„ÂÈ ÙÔ ÚfiÛˆfi ÙÔ˘. ∏ ¯Ú‹ÛË ˘ÓfiÛ·ÎÔ˘ Ú¤ÂÈ Ó· ÂÓÈÛ¯‡ÂÙ·È.

4. ¡· ·ÔʇÁÂÙ·È ÙÔ Î¿ÓÈÛÌ· ÛÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÁ΢ÌÔÛ‡Ó˘ Î·È Ë ¤ÎıÂÛË ÙÔ˘ ‚Ú¤ÊÔ˘˜ ÛÙÔ ·ıËÙÈÎfi οÓÈÛÌ·.

5. ™˘ÓÈÛÙ¿Ù·È ÙÔ ‚Ú¤ÊÔ˜ Ó· ÎÔÈÌ¿Ù·È Û ¯ˆÚÈÛÙfi ÎÚ‚¿ÙÈ, ·ÏÏ¿ ÛÙÔÓ ›‰ÈÔ ¯ÒÚÔ Ì ÙÔ˘˜ ÁÔÓ›˜. ∆· ‚Ú¤ÊË ÌÔÚÔ‡Ó Ó· ÎÔÈÌÔ‡ÓÙ·È ÛÙÔ ÎÚ‚¿ÙÈ ÙˆÓ ÁÔÓÈÒÓ, fiÙ·Ó ·˘ÙÔ› Â›Ó·È Í‡ÓÈÔÈ, ·ÏÏ¿ fi¯È fiÙ·Ó ÎÔÈÌÔ‡ÓÙ·È ‹ Â›Ó·È Ôχ ÎÔ˘Ú·Ṳ̂ÓÔÈ ‹ ˘fi ÙËÓ Â‹ÚÂÈ· Ô˘ÛÈÒÓ. ∏ ÎÔ‡ÓÈ· Ú¤ÂÈ Ó· ÏËÚÔ› ÙȘ ηٿÏÏËϘ ÚԉȷÁڷʤ˜. √ ‡ÓÔ˜ ÙÔ˘ ‚Ú¤ÊÔ˘˜ Û ÔÏ˘ıÚfiÓ· ‹ ηӷ¤ Ú¤ÂÈ Ó· ·ÔʇÁÂÙ·È.

6. ¢›ÓÔ˘Ì È›Ï· ÛÙÔ ‚Ú¤ÊÔ˜, ·Ó ÙË ‰¤¯ÂÙ·È, fiÙ·Ó ÙÔ ‚¿˙Ô˘Ì ÁÈ· ‡ÓÔ, ·ÏÏ¿ ‰ÂÓ ÙËÓ Í·Ó·‰›ÓÔ˘ÌÂ, fiÙ·Ó ¤¯ÂÈ ·ÔÎÔÈÌËı›. ¢ÂÓ Ȥ˙Ô˘Ì ÙÔ ‚Ú¤ÊÔ˜ Ó· ÙËÓ ¿ÚÂÈ, ‰ÂÓ ÙË ‚Ô˘Ù¿Ì Û ÁÏ˘Î¿ ‰È·Ï‡Ì·Ù· Î·È Î·ı˘ÛÙÂÚԇ̠ÙË ¯Ú‹ÛË Ù˘ ÛÙ· ıËÏ¿˙ÔÓÙ· ‚Ú¤ÊË ÌÂÙ¿ ÙÔÓ 1Ô Ì‹Ó· Ù˘ ˙ˆ‹˜.

7. ∞ÔÊ˘Á‹ ˘„ËÏ‹˜ ıÂÚÌÔÎÚ·Û›·˜ ÛÙÔ ‰ˆÌ¿ÙÈÔ Ô˘ ÎÔÈÌ¿Ù·È ÙÔ ‚Ú¤ÊÔ˜. ∆Ô ‚Ú¤ÊÔ˜ Ú¤ÂÈ Ó· Â›Ó·È ÂÏ·ÊÚ¿ ÓÙ˘Ì¤ÓÔ Î·È Ë ıÂÚÌÔÎÚ·Û›· ÙÔ˘ ÂÚÈ‚¿ÏÏÔÓÙÔ˜ Ó· Â›Ó·È Â˘¯¿ÚÈÛÙË ÁÈ· ÂÏ·ÊÚ¿ ÓÙ˘Ì¤ÓÔ ÂÓ‹ÏÈη.

8. ¢ÂÓ Û˘ÓÈÛÙ¿Ù·È Ë ¯ÚËÛÈÌÔÔ›ËÛË Û˘Û΢ÒÓ Û˘Ó¯ԇ˜ ·Ú·ÎÔÏÔ‡ıËÛ˘ ÙÔ˘ ‚Ú¤ÊÔ˘˜ ÛÙÔ Û›ÙÈ, ·Ú¿ ÌfiÓÔ Û ÂÈÏÂÁ̤Ó˜ ÂÚÈÙÒÛÂȘ, ηıÒ˜ ‰ÂÓ ˘¿Ú¯ÂÈ Î·Ó¤Ó· ‰Â‰Ô̤ÓÔ Ô˘ Ó· ‰Â›¯ÓÂÈ fiÙÈ ÌÂÈÒÓÔ˘Ó ÙÔÓ Î›Ó‰˘ÓÔ.

9. °È· ÙËÓ ·ÔÊ˘Á‹ Ù˘ Ï·ÁÈÔÎÂÊ·Ï›·˜ Û˘ÓÈÛٿٷÈ: ·. ∆Ô ‚Ú¤ÊÔ˜ Ó· ÎÔÈÌ¿Ù·È Ì ÙÔ ÎÂÊ¿ÏÈ ÂÓ·ÏÏ¿Í ÛÙÔ ‰ÂÍÈfi ‹ ·ÚÈÛÙÂÚfi Ï¢Úfi ·Ó¿ ‚‰ÔÌ¿‰·. ‚. ∂Óı·ÚÚ‡ÓÂÙ·È Ë ÚËÓ‹˜ ı¤ÛË, fiÙ·Ó ÙÔ ‚Ú¤ÊÔ˜ Â›Ó·È Í‡ÓÈÔ. Á. ¢ÂÓ Û˘ÓÈÛÙ¿Ù·È Ó· ̤ÓÂÈ ÔÏϤ˜ ÒÚ˜ ÛÙÔ ÂȉÈÎfi οıÈÛÌ· ·˘ÙÔÎÈÓ‹ÙÔ˘. ‰. ∏ “fiÚıÈ·” ·ÁηÏÈ¿ Ú¤ÂÈ Ó· ÂÓÈÛ¯‡ÂÙ·È.

Ô˘ ı· Ì·˜ οÓÂÈ Ó· „¿ÍÔ˘Ì ÁÈ· Èı·Ó‹ ηÎÔÔ›ËÛË, ·ÏÏ¿ Ú¤ÂÈ Ó· ¤¯Ô˘Ì ˘fi„Ë Ì·˜ fiÙÈ ÙÔ ·‰ÂÚÊ¿ÎÈ ÙÔ˘ ‚Ú¤ÊÔ˘˜ Ô˘ ¤¯ÂÈ Âı¿ÓÂÈ ·fi ÁÓˆÛÙfi ·›ÙÈÔ ¤¯ÂÈ ·˘ÍË̤ÓÔ Î›Ó‰˘ÓÔ Ó· Âı¿ÓÂÈ ˆ˜ ‚Ú¤ÊÔ˜ ·fi ÙËÓ ›‰È· ·ÈÙ›·, Û˘ÌÂÚÈÏ·Ì‚·ÓÔ̤ÓÔ˘ Î·È ÙÔ˘ SIDS (1). ªÈ· ÔÈÎÔÁ¤ÓÂÈ· Ô˘ ¤¯ÂÈ ÙË ıÏÈ‚ÂÚ‹ ÂÌÂÈÚ›· ÂÓfi˜ SIDS, ¤¯ÂÈ 2-6% ΛӉ˘ÓÔ ÁÈ· ‰Â‡ÙÂÚÔ SIDS (4).

Pediatri Jul-Aug 08

30-07-08

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™‡Ó‰ÚÔÌÔ ·ÈÊÓ›‰ÈÔ˘ ‚ÚÂÊÈÎÔ‡ ı·Ó¿ÙÔ˘

∫¤ÓÙÚ· ÊÚÔÓÙ›‰·˜ ‚ÚÂÊÒÓ Î·È SIDS ∂›Ó·È ÛËÌ·ÓÙÈÎfi Ó· ÂÓËÌÂÚÒÓÔÓÙ·È fiÏÔÈ fiÛÔÈ ·Û¯ÔÏÔ‡ÓÙ·È Ì ÙË ÊÚÔÓÙ›‰· ÙˆÓ ‚ÚÂÊÒÓ Î·È fi¯È ÌfiÓÔ ÔÈ ÁÔÓ›˜. ∂›Ó·È ·ÍÈÔÛËÌ›ˆÙÔ fiÙÈ ÛÙȘ ·ÓÂÙ˘Á̤Ó˜ ¯ÒÚ˜, Ù· 2/3 ÙˆÓ ‚ÚÂÊÒÓ Ô˘ Â›Ó·È ÌÈÎÚfiÙÂÚ· ÙˆÓ 12 ÌËÓÒÓ ‰ÂÓ ÊÚÔÓÙ›˙ÔÓÙ·È ·fi ÙÔ˘˜ ÁÔÓ›˜. ∆Ô 50% ·fi ·˘Ù¿ ÊÚÔÓÙ›˙ÔÓÙ·È ·fi Û˘ÁÁÂÓ›˜, ÙÔ 10% ·fi ÓÙ·ÓÙ¿ Î·È ÙÔ 40% ·fi ·È‰ÈÎÔ‡˜ ÛÙ·ıÌÔ‡˜. ∞fi ÙÔ Û‡ÓÔÏÔ ÙˆÓ ·ÈÊÓ›‰ÈˆÓ ‚ÚÂÊÈÎÒÓ ı·Ó¿ÙˆÓ, 20% Û˘Ì‚·›ÓÂÈ fiÙ·Ó Ù· ‚Ú¤ÊË ‰ÂÓ ÊÚÔÓÙ›˙ÔÓÙ·È ·fi ÙÔ˘˜ ÁÔÓ›˜ Î·È Ì¿ÏÈÛÙ· 7% ·fi ·˘ÙÔ‡˜ Û˘Ì‚·›ÓÂÈ Û ÔÚÁ·ÓˆÌ¤Ó· ΤÓÙÚ· ÊÚÔÓÙ›‰·˜ ‚ÚÂÊÒÓ, ÂÓÒ ÙÔ 13% Û ‚Ú¤ÊË Ô˘ ÊÚÔÓÙ›˙ÔÓÙ·È ·fi ÙÔ Â˘Ú‡ÙÂÚÔ ÔÈÎÔÁÂÓÂÈ·Îfi ÂÚÈ‚¿ÏÏÔÓ (25). ¶Èı·ÓfiÓ ·˘Ùfi ¤¯ÂÈ Ó· ¤¯ÂÈ Ó· οÓÂÈ Ì ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÔÈ ÂÚÁ·˙fiÌÂÓÔÈ Û ÔÚÁ·ÓˆÌ¤Ó· ΤÓÙÚ· ÊÚÔÓÙ›‰·˜ Â›Ó·È Û˘¯ÓfiÙÂÚ· ÌÂÁ·Ï‡ÙÂÚÔÈ, ÈÔ ÌÔÚʈ̤ÓÔÈ Î·È ÈÔ ÂÎ·È‰Â˘Ì¤ÓÔÈ ·fi ÂΛÓÔ˘˜ Ô˘ ÊÚÔÓÙ›˙Ô˘Ó ‚Ú¤ÊË ÛÙÔ Û›ÙÈ. ÕÍÈÔ ·Ó·ÊÔÚ¿˜ Â›Ó·È Â›Û˘ ÙÔ ÁÂÁÔÓfi˜ fiÙÈ ÙÔ ¤Ó· ÙÚ›ÙÔ ÙˆÓ SIDS Û˘Ì‚·›ÓÔ˘Ó ÙËÓ ÚÒÙË Â‚‰ÔÌ¿‰· Ô˘ ÙÔ ‚Ú¤ÊÔ˜ Ê˘Ï¿ÛÛÂÙ·È ·fi ¿ÏÏÔ˘˜ ÂÎÙfi˜ ÙÔ˘˜ ÁÔÓ›˜ Î·È ÔÈ ÌÈÛÔ› ·fi ·˘ÙÔ‡˜ Û˘Ì‚·›ÓÔ˘Ó ÙËÓ ÚÒÙË Ì¤Ú·, ÁÂÁÔÓfi˜ Ô˘ Èı·Ó¿ ·ÓÙ·Ó·ÎÏ¿ ÙËÓ ÂÏÏÈ‹ ÏËÚÔÊfiÚËÛË (25). ∫·Ù¢ı˘ÓÙ‹ÚȘ √‰ËÁ›Â˜ ÁÈ· ÚfiÏË„Ë SIDS √È ÙÂÏÂ˘Ù·›Â˜ Û˘ÛÙ¿ÛÂȘ Ù˘ ∞ÌÂÚÈηÓÈ΋˜ ∞η‰ËÌ›·˜ ¶·È‰È·ÙÚÈ΋˜ (¡Ô¤Ì‚ÚÈÔ˜ ÙÔ˘ 2005) ÁÈ· ÙËÓ ÚfiÏË„Ë ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ÙÔ˘ ·ÈÊÓ›‰ÈÔ˘ ‚ÚÂÊÈÎÔ‡ ı·Ó¿ÙÔ˘ (12,26) ·Ó·Ê¤ÚÔÓÙ·È ÛÙÔÓ ¶›Ó·Î· 3. ÀÔ¯Ú¤ˆÛË ÙˆÓ ·È‰È¿ÙÚˆÓ Â›Ó·È Ë Û˘Ó¯‹˜ ÂÓË̤ڈÛË ÙˆÓ ÁÔÓÈÒÓ Î·È fiÏˆÓ fiÛÔÈ ·Û¯ÔÏÔ‡ÓÙ·È Ì ÙË ÊÚÔÓÙ›‰· ÙˆÓ ‚ÚÂÊÒÓ, Ì ÛÙfi¯Ô ÙËÓ ÂÚ·ÈÙ¤Úˆ Ì›ˆÛË ÙÔ˘ ÙÚ·ÁÈÎÔ‡ Û˘Ì‚¿ÓÙÔ˜ ÙÔ˘ ·ÈÊÓ›‰ÈÔ˘ ‚ÚÂÊÈÎÔ‡ ı·Ó¿ÙÔ˘. µÈ‚ÏÈÔÁÚ·Ê›· 1. Hunt CE, Hauck FR. Sudden infant death syndrome.

CMAJ 2006;174:1861-1869.

2. Lahr MB, Rosenberg KD, Lapidus JA. Bedsharing and maternal smoking in a population-based survey of new mothers. Pediatrics 2005;116:e530-e542.

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8. Thach B. Tragic and sudden death. Potential and proven mechanisms causing sudden infant death syndrome.

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9. Blair PS, Fleming PJ. Recurrence risk of sudden infant death syndrome. Arch Dis Child 2008;93:269-270.

10. Hunt CE. Sudden infant death syndrome and other causes of infant mortality: diagnosis, mechanisms, and risk for recurrence in siblings. Am J Respir Crit Care Med 2001;164:346-357.

11. Sahni R, Schulze KF, Kashyap S, Ohira-Kist K, Fifer WP, Myers MM. Sleeping position and electrocortical activity in low birthweight infants. Arch Dis Child Fetal Neonatal Ed 2005;90:F311-F315.

12. American Academy of Pediatrics Task Force on Sudden Infant Death Syndrome. The changing concept of sudden infant death syndrome: diagnostic coding shifts, controversies regarding the sleeping environment, and new variables to consider in reducing risk. Pediatrics 2005;116:1245-1255.

13. Persing J, James H, Swanson J, Kattwinkel J; American Academy of Pediatrics Committee on Practice and Ambulatory Medicine, Section on Plastic Surgery and Section on Neurological Surgery. Prevention and management of positional skull deformities in infants. American Academy of Pediatrics Committee on Practice and Ambulatory Medicine, Section on Plastic Surgery and Section on Neurological Surgery. Pediatrics 2003;112: 199-202.

14. Blair PS, Ball HL. The prevalence and characteristics associated with parent-infant bed-sharing in England. Arch Dis Child 2004;89:1106-1110.

15. McGarvey C, McDonnell M, Hamilton K, O’Regan M, Matthews T. An 8 year study of risk factors for SIDS: bedsharing versus non-bed-sharing. Arch Dis Child 2006;91: 318-323.

16. Chen A, Rogan WJ. Breastfeeding and the risk of postneonatal death in the United States. Pediatrics 2004;113: e435-e439.

17. Kiechl-Kohlendorfer U, Hof D, Peglow UP, TrawegerRavanelli B, Kiechl S. Epidemiology of apparent life threatening events. Arch Dis Child 2005;90:297-300.

18. McGovern MC, Smith MB. Causes of apparent life threatening events in infants: a systematic review. Arch Dis Child 2004;89:1043-1048.

19. Mitchell EA, Thompson JM. Parental reported apnoea, admissions to hospital and sudden infant death syndrome. Acta Paediatr 2001;90:417-422.

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21. Committee on Fetus and Newborn. American Academy of Pediatrics. Apnea, sudden infant death syndrome, and home monitoring. Pediatrics 2003;111:914-917.

22. McNamara F, Sullivan CE. Obstructive sleep apnea in infants: relation to family history of sudden infant death ¶·È‰È·ÙÚÈ΋ 2008;71:304-310

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syndrome, apparent life-threatening events, and obstructive sleep apnea. J Pediatr 2000;136:318-323.

23. Kahn A; European Society for the Study and Prevention of Infant Death. Recommended clinical evaluation of infants with an apparent life-threatening event. Consensus document of the European Society for the Study and Prevention of Infant Death, 2003. Eur J Pediatr 2004;163: 108-115.

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24. Levene S, Bacon CJ. Sudden unexpected death and covert homicide in infancy. Arch Dis Child 2004;89:443-447.

25. Moon RY, Patel KM, Shaefer SJ. Sudden infant death syndrome in child care settings. Pediatrics 2000;106:295-300.

26. Saririan S, Hauck FR. New recommendations to reduce the risk of SIDS: what should we advise parents? Am Fam Physician 2006;74:1839-1840.

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∂¡¢π∞º∂ƒ√À™∞ ¶∂ƒπ¶∆ø™∏

CASE REPORT

311

™‡Ó‰ÚÔÌÔ ·Ó·ÛÙÚ¤„ÈÌ˘ Ô›ÛıÈ·˜ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜ (PRES): ÂÚÈÁÚ·Ê‹ ‰‡Ô ÂÚÈÙÒÛÂˆÓ Î·È ·Ó·ÛÎfiËÛË Ù˘ ‚È‚ÏÈÔÁÚ·Ê›·˜ µ. ∞ÛÎËÙ‹1, ∞. ªËÙÛÈÒÓË1, ™. ª·ÛÙÚÔÁÈ¿ÓÓË2, ¶. °Ô˘ÚÙ˙ÂÏ›‰Ë˜3, π. ¡›Î·˜4, ∫. ™ÙÂÊ·Ó›‰Ë˜1 ¶ÂÚ›ÏË„Ë: ∏ ·Ó·ÛÙÚ¤„ÈÌË Ô›ÛıÈ· ÂÁÎÂÊ·ÏÔ¿ıÂÈ· (posterior reversible encephalopathy syndrome PRES) Â›Ó·È ÌÈ· ÔÍ›· ÂÁÎÂÊ·ÏÔ¿ıÂÈ· Ô˘ ¤¯ÂÈ ÂÚÈÁÚ·Ê› ÚfiÛÊ·Ù· Î·È ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ·Ó·ÛÙÚ¤„È̘ ·ÂÈÎÔÓÈÛÙÈΤ˜ ‚Ï¿‚˜ ÛÙËÓ ·ÍÔÓÈ΋ ÙÔÌÔÁÚ·Ê›· (CT) Î·È ÙË Ì·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· (MRI) ÂÁÎÂÊ¿ÏÔ˘. √È ‚Ï¿‚˜ ·˘Ù¤˜ ÂÓÙÔ›˙ÔÓÙ·È Û˘Ó‹ıˆ˜ ÛÙȘ Ô›ÛıȘ ÂÚÈÔ¯¤˜ ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘, ÔÊ›ÏÔÓÙ·È Û ·ÁÁÂÈÔÁÂÓ¤˜ Ô›‰ËÌ· Î·È Û˘Û¯ÂÙ›˙ÔÓÙ·È Î˘Ú›ˆ˜ Ì ÔÍ›· ·‡ÍËÛË Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘ Î·È Ì ¯ÔÚ‹ÁËÛË ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÒÓ. ∆· Û˘ÌÙÒÌ·Ù· Ì ٷ ÔÔ›· ÂΉËÏÒÓÂÙ·È Â›Ó·È ÎÂÊ·Ï·ÏÁ›·, Û‡Á¯˘ÛË, Û·ÛÌÔ› Î·È ÔÙÈΤ˜ ‰È·Ù·Ú·¯¤˜. √ Û˘Ó‰˘·ÛÌfi˜ ÙˆÓ ÎÏÈÓÈÎÒÓ Î·È MRI ¢ÚËÌ¿ÙˆÓ Â›Ó·È ‰È·ÁÓˆÛÙÈÎfi˜. ∏ ÔÚı‹ Î·È ¤ÁηÈÚË ‰È¿ÁÓˆÛË Â›Ó·È Ë ÚÔ¸fiıÂÛË ÁÈ· ÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË, ÌÂ Û˘Ó‹ıË ¤Î‚·ÛË ÙËÓ Ï‹ÚË ˘Ô¯ÒÚËÛË ÙˆÓ ÎÏÈÓÈÎÒÓ Î·È ·ÂÈÎÔÓÈÛÙÈÎÒÓ Â˘ÚËÌ¿ÙˆÓ Û 1-2 ‚‰ÔÌ¿‰Â˜. ∆Ô Û‡Ó‰ÚÔÌÔ ·˘Ùfi ¤¯ÂÈ ÂÚÈÁÚ·Ê› ΢ڛˆ˜ Û ÂÓ‹ÏÈΘ, ÂÓÒ ˘¿Ú¯Ô˘Ó ÂÏ¿¯ÈÛÙ˜ ·Ó·ÊÔÚ¤˜ Û ·È‰È¿. ¶·ÚÔ˘ÛÈ¿˙ÔÓÙ·È ‰‡Ô ·È‰È¿ Ì ÙÂÏÈÎfi ÛÙ¿‰ÈÔ ÓÂÊÚÈ΋˜ ·ÓÂ¿ÚÎÂÈ·˜ Î·È PRES ÏfiÁˆ ÔÍ›·˜ Âȉ›ӈÛ˘ Ù˘ ·ÚÙËÚȷ΋˜ ˘¤ÚÙ·Û˘. ∆ÔÓ›˙ÂÙ·È Ë ÛËÌ·Û›· Ù˘ ¤ÁηÈÚ˘ ‰È¿ÁÓˆÛ˘ Î·È ıÂÚ·›·˜ Ì ·ÓÙȸÂÚÙ·ÛÈο Î·È ·ÓÙÈÂÈÏËÙÈο Î·È Ë ÂÍ¿ÏÂÈ„Ë Î¿ı ·ÈÙÈÔÏÔÁÈÎÔ‡ ·Ú¿ÁÔÓÙ·.

1 ¡ÂÊÚÔÏÔÁÈÎfi ∆Ì‹Ì· ¡ÔÛÔÎÔÌ›Ԣ ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡” 2 ¡Â˘ÚÔÏÔÁÈÎfi ∆Ì‹Ì· ¡ÔÛÔÎÔÌ›Ԣ ¶·›‰ˆÓ “¶. & ∞ ∫˘ÚÈ·ÎÔ‡” 3 ¡Â˘ÚÔÏÔÁÈÎfi ∆Ì‹Ì·, 401 °ÂÓÈÎfi ™ÙÚ·ÙȈÙÈÎfi ¡ÔÛÔÎÔÌÂ›Ô ∞ıËÓÒÓ 4 ∆Ì‹Ì· ∞ÎÙÈÓԉȷÁÓˆÛÙÈÎÒÓ ∞ÂÈÎÔÓ›ÛÂˆÓ ¡ÔÛÔÎÔÌ›Ԣ ¶·›‰ˆÓ “∞Á›· ™ÔÊ›·”, ∞ı‹Ó· AÏÏËÏÔÁÚ·Ê›·: µ·Ú‚¿Ú· ∞ÛÎËÙ‹ vaskiti@gmail.com ¡ÂÊÚÔÏÔÁÈÎfi ∆Ì‹Ì· ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”

§¤ÍÂȘ ÎÏÂȉȿ: PRES, Ï¢ÎÔÂÁÎÂÊ·ÏÔ¿ıÂÈ·, Û·ÛÌÔ›, ˘¤ÚÙ·ÛË, Ì·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· ÂÁÎÂÊ¿ÏÔ˘, ·È‰È¿, ÓÂÊÚÈ΋ ·ÓÂ¿ÚÎÂÈ·.

Posterior reversible encephalopathy syndrome: a report of two cases and literature review V. Askiti1, ∞. Mitsioni1, S. ªastroyianni2, P. Gourtzelidis3, π. Nikas4, C. Stefanidis1 Abstract: Reversible posterior encephalopathy syndrome (PRES) is a recently described form of acute encephalopathy with typical reversible radiological findings of bilateral grey and white matter abnormalities suggestive of oedema in the posterior regions of the cerebral hemispheres. The causes are miscellaneous, the commonest being an abrupt increase in blood pressure and treatment with immunosuppressive drugs. The most common clinical symptoms are seizures, severe headaches and mental and visual disturbances. The combination of the clinical features and neuroimaging findings is diagnostic. In most cases, with early diagnosis and appropriate treatment the leukoencephalopathy is reversible within 1-2 weeks. The majority of patients with PRES are adults and it has rarely been described in children.

Two children with end stage renal disease and hypertension-induced PRES are presented. Paediatricians must be aware of this syndrome, as early diagnosis, appropriate therapy and removal of the offending medication may prevent progression to irreversible brain damage.

Key words: PRES, leukoencephalopathy, seizure, hypertension, magnetic resonance imaging, children, renal failure.

∂ÈÛ·ÁˆÁ‹ ∆Ô Û‡Ó‰ÚÔÌÔ Ù˘ Ô›ÛıÈ·˜ ·Ó·ÛÙÚ¤„ÈÌ˘ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜ (reversible posterior encephalopathy syndrome - PRES) Â›Ó·È ÌÈ· ÎÏÈÓÈÎÔ·ÎÙÈÓÔÏÔÁÈ΋ ÔÓÙfiÙËÙ· Ô˘ ·Ú¯Èο ÂÚÈÁÚ¿ÊËΠÙÔ 1996, ˆ˜ Û‡Ó‰ÚÔÌÔ ·Ó·ÛÙÚ¤„ÈÌ˘ Ô›ÛıÈ·˜ Ï¢ÎÔÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜ (1). ∞fi ÙfiÙ ¤¯ÂÈ ÂÚÈÁÚ·Ê› Û ·ÛıÂÓ›˜ Ì ÓÂÊÚ›Ùȉ· ÙÔ˘ χÎÔ˘, ÂÎÏ·Ì„›·, ·ÈÌÔÏ˘ÙÈÎfi Ô˘Ú·ÈÌÈÎfi Û‡Ó‰ÚÔÌÔ, ·ÛıÂÓ›˜ Û ·ÓÔÛÔηٷÛÙ·ÏÙÈ΋ ıÂÚ·-

1 Department of Nephrology, “P. & A. Kyriakou” Children’s Hospital, Athens, Greece 2 Department of Neurology, “P. & A. Kyriakou” Children’s Hospital, Athens, Greece 3 Department of Neurology, 401 General Military Hospital of Athens, Greece 4 Department of Radiodiagnostic Imaging, “Aghia Sofia” Children’s Hospital, Athens, Greece Correspondence: Varvara Askiti vaskiti@gmail.com Department of Nephrology, “P. & A. Kyriakou” Children’s Hospital, Athens, Greece

›· (΢ÎÏÔÛÔÚ›ÓË) Î·È Û ÈÓÙÂÚÊÂÚfiÓË (1,9,13-15). ¶ÔÏÏÔ› ·fi ·˘ÙÔ‡˜ ‹Ù·Ó ÂÓ‹ÏÈΘ, ÂÓÒ Â›Ó·È Û¿ÓȘ ÔÈ ·Ó·ÊÔÚ¤˜ Û ·È‰È¿ (2,5,6,11). ∆· Û˘ÌÙÒÌ·Ù· Ì ٷ ÔÔ›· ÂΉËÏÒÓÂÙ·È Â›Ó·È ÎÂÊ·Ï·ÏÁ›·, Û‡Á¯˘ÛË, Û·ÛÌÔ› Î·È ÔÙÈΤ˜ ‰È·Ù·Ú·¯¤˜. ∆· Ù˘Èο ·ÎÙÈÓÔÏÔÁÈο Â˘Ú‹Ì·Ù· Â›Ó·È ·ÏÏÔÈÒÛÂȘ ÛÙË Ï¢΋ Ô˘Û›· ÙˆÓ Ô›ÛıÈˆÓ ÙÌËÌ¿ÙˆÓ ÙˆÓ ÂÁÎÂÊ·ÏÈÎÒÓ ËÌÈÛÊ·ÈÚ›ˆÓ, ‚ÚÂÁÌ·ÙÔ˚Óȷο, Î·È ıˆÚÔ‡ÓÙ·È ·ÔÙ¤ÏÂÛÌ· ¶·È‰È·ÙÚÈ΋ 2008;71:311-316

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µ. ∞ÛÎËÙ‹ Î·È Û˘Ó.

A

B

∂ÈÎfiÓ· 1. ∞ Î·È µ: FLAIR ·ÎÔÏÔ˘ı›Â˜ ÛÙËÓ MRI ÂÁÎÂÊ¿ÏÔ˘: ·˘ÍË̤ÓË ¤ÓÙ·ÛË Û‹Ì·ÙÔ˜ ÛÙÔ˘˜ ‚ÚÂÁÌ·ÙÈÎÔ‡˜ ÏÔ‚Ô‡˜ Ì ÊÏÔÈÔ¸ÔÊÏÔÈÒ‰Ë ÂÓÙfiÈÛË.

Ôȉ‹Ì·ÙÔ˜ ÛÙȘ ÂÚÈÔ¯¤˜ ·˘Ù¤˜. ∆· ÈÔ Û˘¯Ó¿ ·›ÙÈ· Ô˘ ÚÔηÏÔ‡Ó ÙÔ PRES Â›Ó·È ÔÍ›· ·‡ÍËÛË Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘ (∞¶) Î·È Ë ıÂÚ·›· Ì ·ÓÔÛÔηٷÛÙ·ÏÙÈο. ∞Ó Î·È Ù· ÎÏÈÓÈο Î·È ·ÎÙÈÓÔÏÔÁÈο Â˘Ú‹Ì·Ù· ıˆÚÔ‡ÓÙ·È ÁÂÓÈο ηÏÔ‹ıË Î·È ·Ó·ÛÙÚ¤„ÈÌ·, ¤¯Ô˘Ó ÂÚÈÁÚ·Ê› ÂÚÈÙÒÛÂȘ Ì ÌfiÓÈÌË Ó¢ÚÔÏÔÁÈ΋ ‚Ï¿‚Ë (3-5,8-10). ¶·Ú¿ ÙË ÌÂÁ¿ÏË Â˘·ÈÛıËÙÔÔ›ËÛË, fiÛÔÓ ·ÊÔÚ¿ ÙÔ PRES ÛÙÔ˘˜ ÂÓ‹ÏÈΘ, ÔÈ ·È‰›·ÙÚÔÈ Ê·›ÓÂÙ·È Ó· Â›Ó·È ÏÈÁfiÙÂÚÔ ÂÍÔÈÎÂȈ̤ÓÔÈ Ì ·˘Ù‹ ÙËÓ ÔÓÙfiÙËÙ·. ∏ ¤ÁηÈÚË ‰È¿ÁÓˆÛË Î·È Ë Î·Ù¿ÏÏËÏË ·ÓÙÈÌÂÙÒÈÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ Â›Ó·È ÛËÌ·ÓÙÈ΋ ÁÈ· ÙËÓ ¤Î‚·ÛË Ù˘ Ó¢ÚÔÏÔÁÈ΋˜ ‚Ï¿‚˘. ™Â ·˘Ù‹ ÙË ÌÂϤÙË ·ÚÔ˘ÛÈ¿˙ÔÓÙ·È ‰‡Ô ·È‰È¿ Ì ÙÂÏÈÎfi ÛÙ¿‰ÈÔ ÓÂÊÚÈ΋˜ ·ÓÂ¿ÚÎÂÈ·˜ Î·È PRES, ÏfiÁˆ ÔÍ›·˜ Âȉ›ӈÛ˘ Ù˘ ·ÚÙËÚȷ΋˜ ˘¤ÚÙ·Û˘, ÙÔ ¤Ó· ÌÂ Ù˘Èο Î·È ÙÔ ¿ÏÏÔ Ì ¿Ù˘· Ó¢ÚÔ·ÂÈÎÔÓÈÛÙÈο Â˘Ú‹Ì·Ù·.

A

∞ÛıÂÓ‹˜ 1 ∞ÁfiÚÈ 11 ÂÙÒÓ ÂÈÛ‹¯ıË ÛÙÔ ÓÔÛÔÎÔÌÂ›Ô Ì·˜, ÏfiÁˆ ÂÂÈÛÔ‰›Ô˘ ÁÂÓÈÎÂ˘Ì¤ÓˆÓ ÙÔÓÈÎÔÎÏÔÓÈÎÒÓ Û·ÛÌÒÓ Î·È ·ÎÔÏÔ‡ıˆ˜ ÂÓÙÔÓfiÙ·Ù˘ ÎÂÊ·Ï·ÏÁ›·˜ Î·È Û˘Á¯˘ÙÈÎÒÓ Ê·ÈÓÔ̤ӈÓ. ∞fi ÙËÓ ·ÓÙÈÎÂÈÌÂÓÈ΋ ÂͤٷÛË ‰È·ÈÛÙÒıËΠ¤ÎÙˆÛË ÂÈ¤‰Ô˘ Û˘ÓÂȉ‹Ûˆ˜, Ë ∞¶ ‹Ù·Ó 180/100 mm Hg, ÂÓÒ ·fi ÙËÓ Î·Ù¿ Û˘ÛÙ‹Ì·Ù· ÂͤٷÛË Ô˘‰¤Ó ·ÍÈfiÏÔÁÔ. ∞fi ÙÔ ·ÙÔÌÈÎfi ÙÔ˘ ÈÛÙÔÚÈÎfi ˘Ô‚·ÏÏfiÙ·Ó Û ·ÈÌÔοı·ÚÛË ·fi ¤ÙÔ˘˜. ∆Ô ·Ú¯ÈÎfi ÓfiÛËÌ· Ô˘ ÚÔοÏÂÛ ÙËÓ ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ ÓÂÊÚÈ΋ ·ÓÂ¿ÚÎÂÈ· ‹Ù·Ó ‚·Ï‚›‰Â˜ Ô›ÛıÈ·˜ Ô˘Ú‹ıÚ·˜. ∂›¯Â ˘Ô‚ÏËı› Û ·ÓÂÈÙ˘¯‹ ÌÂÙ·ÌfiÛ¯Â˘ÛË ÓÂÊÚÔ‡, ÏfiÁˆ ‰˘ÛÏÂÈÙÔ˘ÚÁ›·˜ Ù˘ Ô˘ÚÔ‰fi¯Ô˘ ·ÛÙ˘. ¶ÚÈÓ ·fi ÙËÓ ¤Ó·ÚÍË ÙÔ˘ ÂÂÈÛÔ‰›Ô˘, ‚ÚÈÛÎfiÙ·Ó Û ·ÁˆÁ‹ Ì ÂÚ˘ıÚÔÔÈËÙ›ÓË, ·ÓıÚ·ÎÈÎfi ·Û‚¤ÛÙÈÔ, ÂÓ·Ï·Ú›ÏË, ·ÏʷηÏÛȉfiÏË Î·È ÊÂÏÔ‰È›ÓË. ∞fi ÙÔÓ ÂÚÁ·ÛÙËÚÈ·Îfi ¤ÏÂÁ¯Ô ηٿ ÙËÓ ÂÈÛ·ÁˆÁ‹

B

∂ÈÎfiÓ· 2. ∞ Î·È µ: ¶Ï‹Ú˘ ·Ô‰ÚÔÌ‹ ÙˆÓ ·ÏÏÔÈÒÛÂˆÓ Ì›· ‚‰ÔÌ¿‰· ÌÂÙ¿ ÙËÓ ÂÈÙ˘¯‹ Ú‡ıÌÈÛË Ù˘ ∞¶.

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A

B

°

∂ÈÎfiÓ· 3. ∞: T2 ·ÎÔÏÔ˘ı›Â˜ ÛÙËÓ MRI ÂÁÎÂÊ¿ÏÔ˘. ∞ÏÏÔÈÒÛÂȘ ÛÙË Ï¢΋ Ô˘Û›· Ù˘ ·ÚÂÁÎÂÊ·Ï›‰·˜. µ Î·È °: FLAIR ·ÎÔÏÔ˘ı›Â˜ ÛÙËÓ MRI ÂÁÎÂÊ¿ÏÔ˘. ∂Ûٛ˜ ·˘ÍË̤Ó˘ ¤ÓÙ·Û˘ Û‹Ì·ÙÔ˜ ÛÙÔ˘˜ ÈÓÈ·ÎÔ‡˜ (È) Î·È ‚ÚÂÁÌ·ÙÈÎÔ‡˜ ÏÔ‚Ô‡˜ (‚), ÛÙÔ ÌÂÛÔÏfi‚ÈÔ (Ì), ‚·ÛÈο Á¿ÁÁÏÈ· (Á), ·ÚÈÛÙÂÚfi ı¿Ï·ÌÔ (ı) Î·È ¤Ûˆ ο„· (Î) ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘.

‰È·ÈÛÙÒıËÎÂ: °ÂÓÈ΋ ·›Ì·ÙÔ˜: Hb 10,5 g/dl, ÏÂ˘Î¿ ·ÈÌÔÛÊ·›ÚÈ· 8.900/mm3, ·ÈÌÔÂÙ¿ÏÈ· 187.000/mm3, Ô˘Ú›· 102 mg/dl, ÎÚ·ÙÈÓ›ÓË 7,3 mg/dl, ∫ 3,8 mEq/l, Na 134 mEq/l, Ca 9,7 mg/dl, P 4,9 mg/dl, Ï¢ÎÒÌ·Ù· ÔÏÈο 8,2 mg/dl, ·Ï‚Ô˘Ì›ÓË 4,2 mg/dl, CRP 17 mg/dl. ¢ÂÓ ÂÏ‹ÊıË ¤ÏÂÁ¯Ô˜ ÚÂÓ›Ó˘-·Ï‰ÔÛÙÂÚfiÓ˘, ‰Â‰Ô̤ÓÔ˘ fiÙÈ Â›¯Â ÚÔËÁËı› ·Ê·›ÚÂÛË Ê˘ÛÈÎÒÓ ÓÂÊÚÒÓ Î·È ÌÔۯ‡̷ÙÔ˜.

To ÂÁÎÂÊ·ÏÔÁÚ¿ÊËÌ· (∏∂°) ¤‰ÂÈÍ ‰È¿¯˘Ù˜ ‚Ú·‰˘·ÚÚ˘ı̛˜. ∏ ·ÍÔÓÈ΋ ÂÁÎÂÊ¿ÏÔ˘ (CT) ¤‰ÂÈÍ ˘fi˘ÎÓ˜ ÂÚÈÔ¯¤˜ ÛÙÔ˘˜ ‚ÚÂÁÌ·ÙÈÎÔ‡˜ ÏÔ‚Ô‡˜. ™ÙË Ì·ÁÓËÙÈ΋ (MRI) ÂÁÎÂÊ¿ÏÔ˘ ‰È·ÈÛÙÒıËÎ·Ó ·ÏÏÔÈÒÛÂȘ Ì ·˘ÍË̤ÓË ¤ÓÙ·ÛË Û‹Ì·ÙÔ˜ ÛÙȘ T2 Î·È FLAIR ·ÎÔÏÔ˘ı›Â˜ ÛÙÔ˘˜ ‚ÚÂÁÌ·ÙÈÎÔ‡˜ Î·È ÈÓÈ·ÎÔ‡˜ ÏÔ‚Ô‡˜, ΢ڛˆ˜ ‰ÂÍÈ¿ Ì ÊÏÔÈÔ¸ÔÊÏÔÈÒ‰Ë ÂÓÙfiÈÛË (∂ÈÎfiÓ˜ 1∞, 1µ). √ ·ÛıÂÓ‹˜ ·ÓÙÈÌÂÙˆ›ÛıËΠ̠ÁÂÓÈο ˘ÔÛÙËÚÈÎÙÈο ̤ÙÚ·, ·ÓÙÈÂÈÏË-

A

B

ÙÈ΋ ·ÁˆÁ‹ (Ê·ÈÓ˘ÙÔ˚ÓË 6 mg/kg) Î·È Û˘Ó‰˘·ÛÌfi ÔÏÏ·ÏÒÓ ·ÓÙÈ˘ÂÚÙ·ÛÈÎÒÓ Ê·ÚÌ¿ÎˆÓ Ô˘ ÚÔÛÙ¤ıËÎ·Ó ÛÙ·‰È·Î¿, ÏfiÁˆ ·ÓıÂÎÙÈ΋˜ ˘¤ÚÙ·Û˘ (ÂÓ·Ï·Ú›ÏË 2,1 mg/kg/24ˆÚÔ, ÊÂÏÔ‰È›ÓË 0,6 mg/kg/24ˆÚÔ, ˘‰Ú·Ï·˙›ÓË 1,8 mg/kg/‰fiÛË/24ˆÚÔ, ·ÙÂÓÔÏfiÏË 2 mg/kg/24ˆÚÔ, ÎÏÔÓȉ›ÓË patch, ˘ÔÁÏÒÛÛÈ· ÓÈʉÈ›ÓË, Ï·‚ÂÙ·ÏfiÏË 4 mg/kg/24ˆÚÔ, ÌÈÓÔÍȉ›ÏË 10 mg/24ˆÚÔ). ∏ MRI ÂÁÎÂÊ¿ÏÔ˘, Ì›· ‚‰ÔÌ¿‰· ÌÂÙ¿ ÙË Ú‡ıÌÈÛË Ù˘ ∞¶ Î·È Û˘ÓÔÏÈο 40 Ë̤Ú˜ ·fi ÙËÓ ¤Ó·ÚÍË ÙˆÓ Û˘Ìو̿وÓ, ¤‰ÂÈÍ Ï‹ÚË ˘Ô¯ÒÚËÛË ÙˆÓ ·ÏÏÔÈÒÛÂˆÓ ÛÙÔ˘˜ ‚ÚÂÁÌ·ÙÈÎÔ‡˜ Î·È ÈÓÈ·ÎÔ‡˜ ÏÔ‚Ô‡˜ (∂ÈÎfiÓ˜ 2∞, 2µ).

∞ÛıÂÓ‹˜ 2 ∞ÁfiÚÈ 3 ÂÙÒÓ ÌÂٷʤÚıËΠÛÙÔ ÓÔÛÔÎÔÌÂ›Ô Ì·˜ ‡ÛÙÂÚ· ·fi status ÁÂÓÈÎÂ˘Ì¤ÓˆÓ ÙÔÓÈÎÔÎÏÔÓÈÎÒÓ Û·ÛÌÒÓ Î·È ÔÍ›· ˘ÂÚÙ·ÛÈ΋ ÎÚ›ÛË (202/110 mm

°

∂ÈÎfiÓ· 4. ∞, µ, °: ¶Ï‹Ú˘ ˘Ô¯ÒÚËÛË ÙˆÓ ·ÏÏÔÈÒÛÂˆÓ 20 Ë̤Ú˜ ÌÂÙ¿ ÙË Ú‡ıÌÈÛË Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘. ¶·È‰È·ÙÚÈ΋ 2008;71:311-316

Pediatri Jul-Aug 08

30-07-08

15:53

™ÂÏ›‰·314

314

µ. ∞ÛÎËÙ‹ Î·È Û˘Ó.

Hg). ∫·Ù¿ ÙËÓ ÂÈÛ·ÁˆÁ‹ ÙÔ ·È‰› ‹Ù·Ó ‰È·ÛˆÏËӈ̤ÓÔ, Û ηٷÛÙÔÏ‹ Ì A¶ 170/120 mm Hg. ∞fi Ù· ÏÔÈ¿ Û˘ÛÙ‹Ì·Ù· Ô˘‰¤Ó ·ÍÈfiÏÔÁÔ. ∞fi ÙÔ ·ÙÔÌÈÎfi ÙÔ˘ ÈÛÙÔÚÈÎfi ˘Ô‚·ÏÏfiÙ·Ó Û ÂÚÈÙÔÓ·˚΋ οı·ÚÛË ·fi ¤ÙÔ˘˜. ∆Ô ·Ú¯ÈÎfi ÓfiÛËÌ· Ô˘ ÚÔοÏÂÛ ÙËÓ ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ ÓÂÊÚÈ΋ ·ÓÂ¿ÚÎÂÈ· ‹Ù·Ó ·ÌÊÔÙÂÚfiÏ¢ÚË ÓÂÊÚÈ΋ ˘ÔÏ·Û›·. ¶ÚÈÓ ·fi ÙËÓ ¤Ó·ÚÍË ÙÔ˘ ÂÂÈÛÔ‰›Ô˘ ‚ÚÈÛÎfiÙ·Ó Û ·ÁˆÁ‹ Ì ÂÚ˘ıÚÔÔÈËÙ›ÓË, ·ÏʷηÏÛȉfiÏË, ·Ó·ıÚ·ÎÈÎfi ·Û‚¤ÛÙÈÔ Î·È ÂÓ·Ï·Ú›ÏË. ∞fi ÙÔÓ ÂÚÁ·ÛÙËÚÈ·Îfi ¤ÏÂÁ¯Ô: °ÂÓÈ΋ ∞›Ì·ÙÔ˜: ¯ˆÚ›˜ ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·, pH 7,28, HCO3 27 mEq/l, Na 135 mEq/l, K 4,5 mEq/l, Cl 88 mEq/l, Ô˘Ú›· 171 mg/dl, ÎÚ·ÙÈÓ›ÓË 7 mg/dl, ÁÏ˘Îfi˙Ë 133 mg/dl, Ca 8,2 mg/dl, P 10,1 mg/dl, Mg 2,9 mg/dl, Ï¢ÎÒÌ·Ù· ÔÏÈο 5,3 mg/dl, ·Ï‚Ô˘Ì›ÓË 3 mg/dl. H ÂͤٷÛË ÙÔ˘ ÂÁÎÂÊ·ÏÔÓˆÙÈ·›Ô˘ ˘ÁÚÔ‡ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈ΋. ™ÙËÓ MRI ÂÁÎÂÊ¿ÏÔ˘ ‰È·ÈÛÙÒıËÎ·Ó ·ÏÏÔÈÒÛÂȘ Ì ·˘ÍË̤ÓË ¤ÓÙ·ÛË Û‹Ì·ÙÔ˜ ÛÙÔ ÊÏÔÈfi Î·È ÙË Ï¢΋ Ô˘Û›· Ù˘ ·ÚÂÁÎÂÊ·Ï›‰·˜, ÙËÓ ˘ÔÊÏÔÈÒ‰Ë ÌÔ›Ú· Ï¢΋˜ Ô˘Û›·˜ ÙˆÓ ÈÓÈ·ÎÒÓ ÏÔ‚ÒÓ ¿Ìʈ, ÙËÓ ¤Ûˆ Î·È ¤Íˆ ο„· ¿Ìʈ, ÙÔ ÛÏËÓ›Ô ÙÔ˘ ÌÂÛÔÏÔ‚›Ô˘, ηıÒ˜ Î·È ÙÔÓ ·ÚÈÛÙÂÚfi ÎÂÚÎÔÊfiÚÔ ˘Ú‹Ó·, Ô›ÛıÈÔ ı¿Ï·ÌÔ, Î¤Ï˘ÊÔ˜ ‰ÂÍÈ¿ Î·È ·ÚÈÛÙÂÚfi ÈfiηÌÔ (∂ÈÎfiÓ˜ 3∞, 3µ, 3°). √ ·ÛıÂÓ‹˜ ·ÓÙÈÌÂÙˆ›ÛıËΠ̠·ÓÙÈÂÈÏËÙÈ΋ ·ÁˆÁ‹ (Ê·ÈÓ˘ÙÔ˚ÓË 6 mg/kg/24ˆÚÔ) Î·È ·ÓÙȸÂÚÙ·ÛÈ΋ ·ÁˆÁ‹ (˘‰Ú·Ï·˙›ÓË 1,2 mg/kg/‰fiÛË/24ˆÚÔ Î·È ÂÓ·Ï·Ú›ÏË 0,3 mg/kg/24ˆÚÔ). O ¯ÚfiÓÔ˜ Ô˘ ··ÈÙ‹ıËΠÁÈ· Ó· ÂÏÂÁ¯ı› Ë ·ÚÙËÚȷ΋ ˘¤ÚÙ·ÛË ‹Ù·Ó 4 ̤Ú˜. ™Â Ó¤· MRI ÂÁÎÂÊ¿ÏÔ˘, 20 Ë̤Ú˜ ÌÂÙ¿ ÙËÓ ¤Ó·ÚÍË Ù˘ ıÂÚ·›·˜ Î·È 14 Ë̤Ú˜ ÌÂÙ¿ ÙË Ú‡ıÌÈÛË Ù˘ ∞¶, ‰È·ÈÛÙÒıËΠÏ‹Ú˘ ˘Ô¯ÒÚËÛË ÙˆÓ ·ÏÏÔÈÒÛÂˆÓ Ô˘ ÂȂ‚·›ˆÛ ÙË ‰È¿ÁÓˆÛË (∂ÈÎfiÓ˜ 4∞, 4µ, 4°). ⁄ÛÙÂÚ· ·fi 2 ¯ÚfiÓÈ· ÌÂÙ·ÌÔۯ‡ıËΠÂÈÙ˘¯Ò˜ Î·È ‚Ú›ÛÎÂÙ·È Û ·ÁˆÁ‹ Ì ΢ÎÏÔÛÔÚ›ÓË, ÁÓˆÛÙfi ÚԉȷıÂÛÈÎfi ·Ú¿ÁÔÓÙ· ÁÈ· ·Ó¿Ù˘ÍË Û˘Ó‰ÚfiÌÔ˘ PRES. ª¤¯ÚÈ Û‹ÌÂÚ· (3 ¯ÚfiÓÈ· ÌÂÙ¿ ÙË ÌÂÙ·ÌfiÛ¯Â˘ÛË) Ë ›ÂÛ‹ ÙÔ˘ ‚Ú›ÛÎÂÙ·È Û ÈηÓÔÔÈËÙÈο Â›‰·, ‰ÂÓ ¤¯ÂÈ ·Ú·ÙËÚËı› ˘ÔÙÚÔ‹ ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ PRES Î·È Ë MRI ÂÁÎÂÊ¿ÏÔ˘ ‰ÂÓ ·ÚÔ˘ÛÈ¿˙ÂÈ ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·.

™˘˙‹ÙËÛË ∆Ô Û‡Ó‰ÚÔÌÔ ·Ó·ÛÙÚ¤„ÈÌ˘ Ô›ÛıÈ·˜ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·˜ ÂÚÈÁÚ¿ÊËΠÁÈ· ÚÒÙË ÊÔÚ¿ ·fi ÙÔ˘˜ Hinchey Î·È Û˘Ó. ÙÔ 1996. ∆· ÙÂÏÂ˘Ù·›· ¯ÚfiÓÈ· ¤¯ÂÈ Á›ÓÂÈ ÁÓˆÛÙfi Ì ‰È·ÊÔÚÂÙÈΤ˜ ÔÓÔ̷ۛ˜ fiˆ˜ ˘ÂÚÙ·ÛÈ΋ ÂÁÎÂÊ·ÏÔ¿ıÂÈ·, ÂÍȉڈ̷ÙÈ΋ ÂÁÎÂÊ·ÏÔ¿ıÂÈ· (hyperperfusion encephalopathy), Ô›ÛıÈ· ÂÁÎÂÊ·ÏÔ¿ıÂÈ· Î·È Û‡Ó‰ÚÔÌÔ ·Ó·ÛÙÚ¤„ÈÌÔ˘ Ô›ÛıÈÔ˘ ÂÁÎÂÊ·ÏÈÎÔ‡ Ôȉ‹Ì·ÙÔ˜. ∏ ·ÈÊÓ›‰È· ·‡ÍËÛË Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘ ıˆPaediatriki 2008;71:311-316

Ú‹ıËÎÂ Ô ·ÈÙÈÔÏÔÁÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ ÙÔ˘ PRES ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì·˜. ∏ ˘Ô¯ÒÚËÛË ÙˆÓ ·ÂÈÎÔÓÈÛÙÈÎÒÓ Â˘ÚËÌ¿ÙˆÓ, ÌfiÏȘ ÂϤÁ¯ıËÎÂ Ë ∞¶, ˘Ô‰ÂÈÎÓ‡ÂÈ fiÙÈ Ë ˘ÂÚÙ·ÛÈ΋ ÎÚ›ÛË ‹Ù·Ó Ô Î‡ÚÈÔ˜ ·ÈÙÈÔÏÔÁÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ ÙˆÓ ·ÏÏÔÈÒÛˆÓ. ∞Ó¿ÏÔÁ· ‹Ù·Ó Î·È Ù· Â˘Ú‹Ì·Ù· ÚfiÛÊ·Ù˘ ÌÂϤÙ˘ Û 22 ·È‰È¿ (6). ™Ô‚·Ú‹ ·‡ÍËÛË Ù˘ ∞¶ ·ÚÔ˘Û›·Û·Ó 13/22 ·È‰È¿. ∞fi Ù· ˘fiÏÔÈ· 9 ·È‰È¿ Ì PRES, 5 ›¯·Ó ‹È· ˘¤ÚÙ·ÛË, ÂÓÒ 4 ·È‰È¿ ›¯·Ó Ê˘ÛÈÔÏÔÁÈ΋ ∞¶. ∞˘Ùfi ÌÔÚ› Ó· ÛËÌ·›ÓÂÈ fiÙÈ Ë ·ÈÊÓ›‰È· ·‡ÍËÛË Ù˘ ∞¶ Â›Ó·È ÈÔ ÛËÌ·ÓÙÈ΋ ·fi ÙËÓ ·fiÏ˘ÙË ÙÈÌ‹ Ù˘ Î·È fiÙÈ Èı·ÓÒ˜ ¿ÏÏÔÈ ·ıÔÁfiÓÔÈ ·Ú¿ÁÔÓÙ˜, ·ÓÂÍ¿ÚÙËÙÔÈ Ù˘ ∞¶, fiˆ˜ Ù· ·ÓÔÛÔηٷÛÙ·ÏÙÈο (΢ÎÏÔÛÔÚ›ÓË, tacrolimus Î.¿.), Û˘Ì‚¿ÏÏÔ˘Ó ÛÙËÓ ·ıÔÁ¤ÓÂÈ· ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ (6,14,15). √È ÌÂÙ·‚ÔÏÈΤ˜ ‰È·Ù·Ú·¯¤˜ ÙÔ˘ ÙÂÏÈÎÔ‡ ÛÙ·‰›Ô˘ Ù˘ ¯ÚfiÓÈ·˜ ÓÂÊÚÈ΋˜ ·ÓÂ¿ÚÎÂÈ·˜ ¤¯Ô˘Ó ÂÓÔ¯ÔÔÈËı› ˆ˜ ·ÓÂÍ¿ÚÙËÙÔ˜ ÚԉȷıÂÛÈÎfi˜ ·Ú¿ÁÔÓÙ·˜. ∏ ·ıÔÊ˘ÛÈÔÏÔÁ›· ÙÔ˘ PRES Â›Ó·È Û‡ÓıÂÙË. H ·˘ÙÔÚ˘ıÌÈÛÙÈ΋ ÈηÓfiÙËÙ· ÙˆÓ ÂÁÎÂÊ·ÏÈÎÒÓ ·ÁÁ›ˆÓ ‰È·ÙËÚ› ÛÙ·ıÂÚ‹ ÙËÓ ÂÁÎÂÊ·ÏÈ΋ ÚÔ‹ ·›Ì·ÙÔ˜ fiÙ·Ó Ë Ì¤ÛË ·ÚÙËÚȷ΋ ›ÂÛË Î˘Ì·›ÓÂÙ·È ·Ó¿ÌÂÛ· Û 60120 mm Hg, ÚÔÛٷهÔÓÙ·˜ ¤ÙÛÈ ÙÔÓ ÂÁΤʷÏÔ ·fi ·fiÙÔ̘ ·ÏÏ·Á¤˜ Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘. ∫·ıÒ˜ Ë Ì¤ÛË ·ÚÙËÚȷ΋ ›ÂÛË ·˘Í¿ÓÂÙ·È ·Ú¯Èο, Ë ÂÁÎÂÊ·ÏÈ΋ ·ÁÁÂÈÔÛ‡Û·ÛË ÂÌÔ‰›˙ÂÈ ÙËÓ ÂÁÎÂÊ·ÏÈ΋ ˘ÂډȋıËÛË. ™Â ˘„ËÏfiÙÂÚ· Â›‰· ̤Û˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘, Ë ·˘ÙÔÚ˘ıÌÈÛÙÈ΋ ÈηÓfiÙËÙ· ÙˆÓ ÂÁÎÂÊ·ÏÈÎÒÓ ·ÁÁ›ˆÓ ηٷÚÁ›ٷÈ, Ì Â·ÎfiÏÔ˘ıÔ ÙËÓ Î·Ù¿ÚÁËÛË ÙÔ˘ ·ÈÌ·ÙÔÂÁÎÂÊ·ÏÈÎÔ‡ ÊÚ·ÁÌÔ‡, Ì ·ÔÙ¤ÏÂÛÌ· ÙËÓ ÂÌÊ¿ÓÈÛË ÂÁÎÂÊ·ÏÈÎÔ‡ Ôȉ‹Ì·ÙÔ˜ ‹/Î·È ÂÙ¯ÂȈ‰ÒÓ ·ÈÌÔÚÚ·ÁÈÒÓ. ∫ÏÈÓÈΤ˜ Î·È ·ÂÈÎÔÓÈÛÙÈΤ˜ ·Ú¿ÌÂÙÚÔÈ ‰Â›¯ÓÔ˘Ó fiÙÈ ÙÔ ·ÁÁÂÈ·Îfi ÂÓ‰Ôı‹ÏÈÔ ÛÙȘ ‚ÚÂÁÌ·ÙÈΤ˜ Î·È ÈÓȷΤ˜ ÂÚÈÔ¯¤˜ ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘ Â›Ó·È ÈÔ Â˘·›ÛıËÙÔ ÛÙËÓ ˘¤ÚÙ·ÛË Î·È ÙȘ ΢ÙÙ·ÚÔÙÔÍÈΤ˜ ÂȉڿÛÂȘ ÙˆÓ ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÒÓ. ∂ÓÙÔ‡ÙÔȘ, Ë ÂÓÙfiÈÛË Î·È Û ¿ÏϘ ÂÚÈÔ¯¤˜ ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘ ‰ËÏÒÓÂÈ fiÙÈ ·Ó¿ÏÔÁ· Ì ÙË ÛÔ‚·ÚfiÙËÙ· Ù˘ ˘¤ÚÙ·Û˘ ÔÈ ·˘ÙÔÚ˘ıÌÈÛÙÈÎÔ› Ì˯·ÓÈÛÌÔ› ÌÔÚ› Ó· ηٷÚÁËıÔ‡Ó Û ÔÔÈ·‰‹ÔÙ ÂÚÈÔ¯‹ ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘. ªÂ ÙË Ê·ÛÌ·ÙÔÛÎÔ›· ÚˆÙÔÓ›ˆÓ (proton MRI spectroscopy) Ê¿ÓËΠfiÙÈ ÙÔ PRES ÚÔηÏ› ‰È¿¯˘Ù˜ ÌÂÙ·‚ÔÏÈΤ˜ ·ÓˆÌ·Ï›Â˜ ÛÙÔÓ ÂÁΤʷÏÔ, ·ÎfiÌË Î·È fiÙ·Ó Ë MRI ÂÁÎÂÊ¿ÏÔ˘ Â›Ó·È Ê˘ÛÈÔÏÔÁÈ΋ (6). ø˜ ÂÎ ÙÔ‡ÙÔ˘, ÛÙÔ ËÏÂÎÙÚÔÂÁÎÂÊ·ÏÔÁÚ¿ÊËÌ· ÌÔÚ› Ó· ·Ú·ÙËÚËıÔ‡Ó ‰È¿¯˘Ù˜ ‚Ú·‰˘ÚÚ˘ı̛˜ (fiˆ˜ ÛÙÔ˘˜ ·ÛıÂÓ›˜ Ì·˜) ‹ ÌfiÓÔ ÂÛÙȷο Â˘Ú‹Ì·Ù· (6). ŸÛÔÓ ·ÊÔÚ¿ ÙËÓ ÎÏÈÓÈ΋ Û˘Ìو̷ÙÔÏÔÁ›·, Î·È ÔÈ ‰‡Ô ·ÛıÂÓ›˜ Ì·˜ ·ÚÔ˘Û›·Û·Ó ÁÂÓÈÎÂ˘Ì¤ÓÔ˘˜ ÙÔÓÈÎÔÎÏÔÓÈÎÔ‡˜ Û·ÛÌÔ‡˜, ηıÒ˜ Î·È ¤ÓÙÔÓË ÎÂÊ·Ï·ÏÁ›·, ÂÌ‚Ô¤˜ ÒÙˆÓ Î·È ÔÙÈΤ˜ ‰È·Ù·Ú·¯¤˜. µ¿ÛÂÈ Ù˘ ‚È‚ÏÈÔÁÚ·Ê›·˜, ÔÈ Û·ÛÌÔ› Â›Ó·È ÙÔ Û˘¯ÓfiÙÂÚÔ ÎÏÈÓÈÎfi Û‡Ìو̷ ÙÔ˘ PRES (6). ¶Èı·ÓfiÓ, ·ÛıÂÓ›˜

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30-07-08

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Ô˘ ·ÚÔ˘ÛÈ¿˙Ô˘Ó Ó·˘Ù›·, Â̤ÙÔ˘˜ Î·È ÎÂÊ·Ï·ÏÁ›·, ·ÏÏ¿ ‰ÂÓ ÂÌÊ·Ó›˙Ô˘Ó Û·ÛÌÔ‡˜, Ó· ‰È·Ê‡ÁÔ˘Ó Ù˘ ÚÔÛÔ¯‹˜ Î·È Ó· ·Ú·Ì¤ÓÔ˘Ó ·‰È¿ÁÓˆÛÙÔÈ. ∆· ·ÂÈÎÔÓÈÛÙÈο Â˘Ú‹Ì·Ù· ·fi ÙȘ ÚÒÙ˜ ÌÂϤÙ˜ ·ÛıÂÓÒÓ Ì CT Î·È MRI ÂÁÎÂÊ¿ÏÔ˘ ¤‰ÂÈÍ·Ó fiÙÈ ÔÈ ‚Ï¿‚˜ ÂÚÈÔÚ›˙ÔÓÙ·Ó ÛÙË Ï¢΋ Ô˘Û›· ÙˆÓ Ô›ÛıÈˆÓ ÂÚÈÔ¯ÒÓ ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘, ȉȷ›ÙÂÚ· ÛÙȘ ‚ÚÂÁÌ·ÙÔ˚ÓȷΤ˜ ÂÚÈÔ¯¤˜ (1,3,5,7). ŸÌˆ˜, ÈÔ ÚfiÛÊ·Ù· Î·È Î˘Ú›ˆ˜ Û ·È‰È·ÙÚÈΤ˜ ÌÂϤÙ˜ (5,11), ·Ó·Ê¤ÚÂÙ·È ‰È¿¯˘ÙË Û˘ÌÌÂÙÔ¯‹ ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘, Û˘ÌÂÚÈÏ·Ì‚·ÓÔ̤ÓÔ˘ ÙÔ˘ ÂÁÎÂÊ·ÏÈÎÔ‡ ÛÙÂϤ¯Ô˘˜ Î·È Ù˘ ·ÚÂÁÎÂÊ·Ï›‰·˜, ηıÒ˜ Î·È ÂÎÙÂÙ·Ì¤ÓˆÓ ·ÏÏÔÈÒÛÂˆÓ ÛÙË Ê·È¿ Ô˘Û›· ÙÔ˘ ÂÁÎÂÊ¿ÏÔ˘. ™ÙË ÌÂϤÙË ÙˆÓ Prasad Î·È Û˘Ó. (5) ·Ó·Ê¤ÚÂÙ·È fiÙÈ 9/16 ·È‰È¿ Ì PRES ·ÚÔ˘Û›·˙·Ó ÙȘ Ù˘ÈΤ˜ ·ÏÏÔÈÒÛÂȘ ÛÙÔ˘˜ ÈÓÈ·ÎÔ‡˜ Î·È ‚ÚÂÁÌ·ÙÈÎÔ‡˜ ÏÔ‚Ô‡˜, 2/16 ·ÚÔ˘Û›·˙·Ó ·ÏÏÔÈÒÛÂȘ ÛÙÔ ÂÁÎÂÊ·ÏÈÎfi Û٤ϯԘ, 2/16 ·ÛıÂÓ›˜ ‰È¿¯˘Ù˜ ·ÏÏÔÈÒÛÂȘ ÛÙË Ê·È¿ Î·È Ï¢΋ Ô˘Û›·, ÂÓÒ ·ÈÌÔÚÚ·ÁÈ΋ ‚Ï¿‚Ë ‰È·ÈÛÙÒıËΠ۠3/16 ·ÛıÂÓ›˜. √ ·ÛıÂÓ‹˜ 1 ·ÚÔ˘Û›·˙ ٷ ¯·Ú·ÎÙËÚÈÛÙÈο Ó¢ÚÔ·ÂÈÎÔÓÈÛÙÈο Â˘Ú‹Ì·Ù· ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ PRES, Ù· ÔÔ›· Â›Ó·È Ô›‰ËÌ· ÛÙË Ï¢΋ Ô˘Û›· ÛÙȘ Ô›ÛıȘ ÂÚÈÔ¯¤˜ ÙˆÓ ÂÁÎÂÊ·ÏÈÎÒÓ ËÌÈÛÊ·ÈÚ›ˆÓ Î·È ÂȉÈο ÛÙȘ ‚ÚÂÁÌ·ÙÔ˚ÓȷΤ˜ ÂÚÈÔ¯¤˜. √È ÂÚÈÔ¯¤˜ ÙÔ˘ ÈÓÈ·ÎÔ‡ ÏÔ‚Ô‡ ÂÚ› ÙË Ì¤ÛË ÁÚ·ÌÌ‹ Î·È ÙËÓ ÏËÎÙÚ·›· Û¯ÈÛÌ‹ ‰ÂÓ Û˘ÌÌÂÙ¤¯Ô˘Ó ÛÙÔ PRES Î·È ·˘Ùfi ‚ÔËı¿ÂÈ ÛÙË ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ·fi ¤ÌÊÚ·ÎÙÔ Ù˘ Ô›ÛıÈ·˜ ÂÁÎÂÊ·ÏÈ΋˜ ·ÚÙËÚ›·˜ (2). O ·ÛıÂÓ‹˜ 2, ÂÎÙfi˜ ·fi ÙȘ Ù˘ÈΤ˜ ÁÈ· ÙÔ Û‡Ó‰ÚÔÌÔ ·ÏÏÔÈÒÛÂȘ ÛÙÔ˘˜ ÈÓÈ·ÎÔ‡˜ ÏÔ‚Ô‡˜ ¿Ìʈ, ·ÚÔ˘Û›·˙Â Û˘ÌÌÂÙÔ¯‹ ¿ÏÏˆÓ ÂÚÈÔ¯ÒÓ, ÔÈ Ôԛ˜ ¤¯Ô˘Ó ÂÚÈÁÚ·Ê› Û·ÓÈfiÙÂÚ·, fiˆ˜ ÙÔ ÌÂÛÔÏfi‚ÈÔ, Ë ·ÚÂÁÎÂÊ·Ï›‰·, Ù· ‚·ÛÈο Á¿ÁÁÏÈ· Î·È Ë ¤Ûˆ Î·È Ë ¤Íˆ ο„·. ∆· Â˘Ú‹Ì·Ù¿ Ì·˜, fiˆ˜ Î·È ·˘Ù¿ Ù˘ ÈÔ ÚfiÛÊ·Ù˘ ‚È‚ÏÈÔÁÚ·Ê›·˜ (5,11) ÌÔÚ› Ó· ÔÊ›ÏÔÓÙ·È Û ¯Ú‹ÛË Ù¯ÓÈÎÒÓ Ì ÌÂÁ·Ï‡ÙÂÚË Â˘·ÈÛıËÛ›· ‹ Ó· ·ÓÙ·Ó·ÎÏÔ‡Ó ‰È·ÊÔÚÂÙÈ΋ ÂÓÙfiÈÛË ÙˆÓ ·ÏÏÔÈÒÛÂˆÓ ÛÙ· ·È‰È¿ Û ۯ¤ÛË Ì ÙÔ˘˜ ÂÓ‹ÏÈΘ. ∏ ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ÙÔ˘ PRES ÂÚÈÏ·Ì‚¿ÓÂÈ ÊÏÂ‚Ò‰Ë ıÚfiÌ‚ˆÛË, ·ÔÌ˘ÂÏÈÓˆÙÈΤ˜ ÓfiÛÔ˘˜, ·ÁÁÂÈ›Ùȉ· Î·È ÂÁÎÂÊ·Ï›Ùȉ· (6). ∏ ÛÙÂÓ‹ Û˘ÓÂÚÁ·Û›· ÎÏÈÓÈÎÔ‡ ÁÈ·ÙÚÔ‡ Î·È ·ÎÙÈÓÔÏfiÁÔ˘ ı· ‚ÔËı‹ÛÂÈ ÛÙËÓ ¤ÁηÈÚË Â˘·ÈÛıËÙÔÔ›ËÛË ÁÈ· ÙÔ PRES Î·È ÙËÓ ·ÔÊ˘Á‹ ÂÚÈÙÙÒÓ Î·È ÂÂÌ‚·ÙÈÎÒÓ ÂÍÂÙ¿ÛˆÓ. ∏ ‰È¿ÁÓˆÛË ÙÂÎÌËÚÈÒÓÂÙ·È ÏfiÁˆ Ù˘ ·ÚÔ˘Û›·˜ ˘¤ÚÙ·Û˘ ‹ ÙˆÓ ¿ÏÏˆÓ ÁÓˆÛÙÒÓ ÚԉȷıÂÛÈÎÒÓ ·Ú·ÁfiÓÙˆÓ, ÙˆÓ ·ÂÈÎÔÓÈÛÙÈÎÒÓ Â˘ÚËÌ¿ÙˆÓ ÛÙËÓ MRI ÂÁÎÂÊ¿ÏÔ˘ Î·È Ù˘ ·Ó·ÛÙÚ„ÈÌfiÙËÙ·˜ ÙˆÓ ·ÏÏÔÈÒÛÂˆÓ ÌfiÏȘ ˘Ô¯ˆÚ‹ÛÂÈ Ô ·ÈÙÈÔÏÔÁÈÎfi˜ ·Ú¿ÁÔÓÙ·˜. ∏ ¤Î‚·ÛË ÙˆÓ ·ÛıÂÓÒÓ Ì PRES Â›Ó·È Û˘Ó‹ıˆ˜ ηϋ. ∫·È ÔÈ ‰‡Ô ·ÛıÂÓ›˜ Ì·˜ ·ÚÔ˘Û›·Û·Ó Ï‹ÚË ˘Ô¯ÒÚËÛË ÙˆÓ ÎÏÈÓÈÎÒÓ Î·È ·ÂÈÎÔÓÈÛÙÈÎÒÓ Â˘ÚË-

Ì¿ÙˆÓ ÌÂÙ¿ ÙË Ú‡ıÌÈÛË Ù˘ ·ÚÙËÚȷ΋˜ ›ÂÛ˘. ∏ ÎÏÈÓÈ΋ Î·È Ó¢ÚÔ·ÂÈÎÔÓÈÛÙÈ΋ ·Ó·ÛÙÚ„ÈÌfiÙËÙ· ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ¤¯ÂÈ Â˘Ú¤ˆ˜ ÂÚÈÁÚ·Ê›. ∂ÓÙÔ‡ÙÔȘ, ·Ó ‰ÂÓ ˘¿ÚÍÂÈ ¤ÁηÈÚË ıÂÚ·¢ÙÈ΋ ·Ú¤Ì‚·ÛË, ÙÔ ÏÂÈÙÔ˘ÚÁÈÎfi ÂÁÎÂÊ·ÏÈÎfi Ô›‰ËÌ· ÌÔÚ› Ó· ÌÂÙ·ÙÚ·› Û ΢ÙÙ·ÚÔÙÔÍÈÎfi ÂÁÎÂÊ·ÏÈÎfi Ô›‰ËÌ· Ì ÌfiÓÈ̘ Ó¢ÚÔÏÔÁÈΤ˜ ‚Ï¿‚˜. √ Covarrubias (8) ·Ó¤ÊÂÚ ÌfiÓÈ̘ Ó¢ÚÔÏÔÁÈΤ˜ ‚Ï¿‚˜ Î·È Û ÌÂÚÈΤ˜ ÂÚÈÙÒÛÂȘ ı·Ó·ÙËÊfiÚÔ ¤Î‚·ÛË Û ¤Ó· ٤ٷÚÙÔ ÂÚ›Ô˘ ÙˆÓ ·ÛıÂÓÒÓ ÙÔ˘. ™Â ·È‰È·ÙÚÈΤ˜ ÛÂÈÚ¤˜, ÔÈ Kwon Î·È Û˘Ó. (9) ·Ó¤ÊÂÚ·Ó fiÙÈ 1/12 ·ÛıÂÓ›˜ ·ÚÔ˘Û›·Û ÌfiÓÈÌË ÔÙÈ΋ ‰È·Ù·Ú·¯‹ (¤ÏÏÂÈÌÌ· ÛÙ· ÔÙÈο ‰›·) Î·È ˘ÔÏÂÈÌÌ·ÙÈΤ˜ ÂÓ·Ôı¤ÛÂȘ ·ÈÌÔÛȉËÚ›Ó˘ ÛÙËÓ Â·Ó·ÏËÙÈ΋ MRI ÂÁÎÂÊ¿ÏÔ˘. ∞Ó¿ÏÔÁ· ‹Ù·Ó Ù· Â˘Ú‹Ì·Ù· Î·È ¿ÏÏˆÓ ÌÂÏÂÙÒÓ (5,10). ∞fi ÙȘ ·Ú·¿Óˆ ÌÂϤÙ˜ Ê·›ÓÂÙ·È fiÙÈ Î·ı˘ÛÙÂÚË̤ÓË ‰È¿ÁÓˆÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘, ·ÓÂ·Ú΋˜ ¤ÏÂÁ¯Ô˜ Ù˘ ˘¤ÚÙ·Û˘, ·Ú·ÙÂٷ̤ÓÔÈ Û·ÛÌÔ›, ·‰˘Ó·Ì›· Ó· ‰ÈÔÚıˆı› Ô ·ÈÙÈÔÏÔÁÈÎfi˜ ÌÂÙ·‚ÔÏÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ ‹ Ë ÂÈÌÔÓ‹ ÛÙË ¯Ú‹ÛË ÙˆÓ ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÒÓ Ê·ÚÌ¿ÎˆÓ ÌÔÚ› Ó· ÚÔηϤÛÔ˘Ó ÌË ·Ó·ÛÙÚ¤„ÈÌË ‚Ï¿‚Ë Î·È ÂÁÎÂÊ·ÏÈο ¤ÌÊÚ·ÎÙ·. ø˜ ‰˘ÛÌÂÓ‹ ·ÂÈÎÔÓÈÛÙÈο Â˘Ú‹Ì·Ù· ·Ó·Ê¤ÚÔÓÙ·È Ë ‡·ÚÍË ·ÈÌÔÚÚ·Á›·˜ ‹ ÂÌÊÚ¿ÎÙÔ˘ ÛÙËÓ ·Ú¯È΋ MRI ÂÁÎÂÊ¿ÏÔ˘, ηıÒ˜ Î·È ÔÈ ÂÎÙÂٷ̤Ó˜ ‚Ï¿‚˜ ÛÙȘ ∆2 ·ÎÔÏÔ˘ı›Â˜ (8,12). ∞ÓÙ›ıÂÙ·, ‰ÂÓ ‰È·ÈÛÙÒıËÎÂ Û˘Û¯¤ÙÈÛË Ù˘ ¤Î‚·Û˘ Ì ÙËÓ ËÏÈΛ·, ÙËÓ ·ÈÙÈÔÏÔÁ›· Î·È ÙË ÛÔ‚·ÚfiÙËÙ· Ù˘ ˘¤ÚÙ·Û˘ (5). ∞˘Ùfi ÂÓÈÛ¯‡ÂÙ·È Î·È ·fi Ù· ‰Èο Ì·˜ Â˘Ú‹Ì·Ù·, fiÔ˘ ·Ú¿ ÙË ‰˘ÛÎÔÏ›· Ó· ÂÏÂÁ¯ı› Ë ·ÚÙËÚȷ΋ ›ÂÛË ÛÙÔÓ ·ÛıÂÓ‹ 1, ÔÈ ·ÏÏÔÈÒÛÂȘ ›¯·Ó Ï‹Úˆ˜ ˘Ô¯ˆÚ‹ÛÂÈ ÌÈ· ‚‰ÔÌ¿‰· ÌÂÙ¿ ÙË Ú‡ıÌÈÛË Ù˘ ∞¶. ⁄ÛÙÂÚ· ·fi 4 (·ÛıÂÓ‹˜ 1) Î·È 5 ¯ÚfiÓÈ· ·Ú·ÎÔÏÔ‡ıËÛ˘ (·ÛıÂÓ‹˜ 2) ηӤӷ˜ ·fi ÙÔ˘˜ ·ÛıÂÓ›˜ Ì·˜ ‰ÂÓ ¤¯ÂÈ ·ÚÔ˘ÛÈ¿ÛÂÈ ˘ÔÙÚÔ‹ ÙÔ˘ PRES. £· Ú¤ÂÈ Ó· ÛËÌÂȈı› fiÙÈ Ô ·ÛıÂÓ‹˜ 2 Ï·Ì‚¿ÓÂÈ ·fi ÙÚÈÂÙ›·˜ ΢ÎÏÔÛÔÚ›ÓË, ÁÓˆÛÙfi fiˆ˜ ÚԷӷʤÚıËΠÚԉȷıÂÛÈÎfi ·Ú¿ÁÔÓÙ· ·Ó¿Ù˘Í˘ PRES. ¶·ÚÔÌÔ›ˆ˜ ÛÙË ‚È‚ÏÈÔÁÚ·Ê›· Û¿ÓÈ· ÂÌÊ·Ó›˙ÂÙ·È ˘ÔÙÚÔ‹ Û ·ÛıÂÓ›˜ Ì PRES (6,11). ¶·Ú·Ì¤ÓÂÈ ·‰È¢ÎÚ›ÓÈÛÙÔ ·Ó ÁÈ· οı ˘ÔÙÚÔÈ¿˙ÔÓ ÂÂÈÛfi‰ÈÔ Ô Ô˘‰fi˜ ÁÈ· ÙÔ PRES ¯·ÌËÏÒÓÂÈ ‹ ·Ó ÁÈ· οı ·ÛıÂÓ‹ ··ÈÙÂ›Ù·È Û˘ÁÎÂÎÚÈ̤ÓÔ˜ ÚԉȷıÂÛÈÎfi˜ ·Ú¿ÁÔÓÙ·˜ ‹ ·Ó ‰È·ÊÔÚÂÙÈÎÔ› ·Ú¿ÁÔÓÙ˜ ·fi ÎÔÈÓÔ‡ ÌÔÚÔ‡Ó Ó· ÚÔηϤÛÔ˘Ó ÙÔ PRES. ∂›Û˘, ÛÙÔ Ì¤ÏÏÔÓ ı· Ú¤ÂÈ Ó· ‰È¢ÎÚÈÓÈÛı› ·Ó ÔÈ ·Ú¿ÁÔÓÙ˜ ÎÈÓ‰‡ÓÔ˘ ÁÈ· ˘ÔÙÚÔ‹ Î·È ÌfiÓÈÌË Ó¢ÚÔÏÔÁÈ΋ ‚Ï¿‚Ë ÛÙ· ·È‰È¿ Ì PRES ‰È·Ê¤ÚÔ˘Ó ÛÙ· ·È‰È¿ Ì PRES Û ۯ¤ÛË Ì ÙÔ˘˜ ÂÓ‹ÏÈΘ (6,11). ™˘ÌÂÚ·ÛÌ·ÙÈο, ı· Ú¤ÂÈ Ó· Ù›ıÂÙ·È ÈÛ¯˘Ú‹ ˘Ô„›· ÁÈ· Û‡Ó‰ÚÔÌÔ PRES Û ·È‰È¿ Ô˘ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ˘¤ÚÙ·ÛË ‹ ‚Ú›ÛÎÔÓÙ·È Û ıÂÚ·›· Ì ·ÓÔÛÔηٷÛÙ·ÏÙÈÎÔ‡˜ ·Ú¿ÁÔÓÙ˜ (΢ڛˆ˜ ΢ÎÏÔÛÔÚ›ÓË ¶·È‰È·ÙÚÈ΋ 2008;71:311-316

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µ. ∞ÛÎËÙ‹ Î·È Û˘Ó.

Î·È tacrolimus) Î·È ·ÚÔ˘ÛÈ¿˙Ô˘Ó ·ÈÊÓ›‰È· Ó¢ÚÔÏÔÁÈ΋ ÛËÌÂÈÔÏÔÁ›·. ∏ ηχÙÂÚË Î·Ù·ÓfiËÛË ·˘ÙÔ‡ ÙÔ˘ Û‡ÓıÂÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ ı· Û˘ÓÙÂϤÛÂÈ ÛÙËÓ ¤ÁηÈÚË Î·È Î·Ù¿ÏÏËÏË ıÂÚ·¢ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ÌÈÎÚÒÓ ·ÛıÂÓÒÓ Î·È ÙËÓ ·ÔÊ˘Á‹ ¿ÛÎÔˆÓ Î·È ÂÂÌ‚·ÙÈÎÒÓ ÂÍÂÙ¿ÛˆÓ.

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3. ∞ntunes NL, Small TN, George D, Boulad F, Lis E. Posterior leukoencephalopathy syndrome may not be reversible.

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14. Idilman R, De Maria N, Kugelmas M, Colantoni A, Van Thiel DH. Immunosuppressive drug-induced leukoencephalopathy in patients with liver transplant. Eur J Gastroenterol Hepatol 1998;10:433-436.

15. Tweddle DA, Windebank KP, Hewson QC, Yule SM. Cyclosporin neurotoxicity after chemotherapy. BMJ 1999; 318:1113.

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CASE REPORT

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™‡Ó‰ÚÔÌÔ McCune-Albright. ¶ÂÚÈÁÚ·Ê‹ ÂÚ›ÙˆÛ˘ µ. ∞ÁÁÂÏ¿ÎÔ˘1, ∫. ∞Ó˘Ê·ÓÙ¿Î˘2, ∞. ™Ù·Ì·Ù¿ÎË3, ∂. ∫fiÎÔÚË1, ¶. ¶··¯ÈÏϤˆ˜4, Ã. ÷Ù˙Ë·ı·Ó·Û›Ô˘† ¶ÂÚ›ÏË„Ë: ∏ ÎÏ·ÛÈ΋ ÙÚÈ¿‰· ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ McCune-Albright (MAS) ÂÚÈÏ·Ì‚¿ÓÂÈ ÈÓÒ‰Ë ‰˘ÛÏ·Û›· ÙˆÓ ÔÛÙÒÓ, ˘¤Ú¯ÚˆÛË ÙÔ˘ ‰¤ÚÌ·ÙÔ˜ (café-au-lait ÎËÏ›‰Â˜) Î·È ·˘ÙfiÓÔÌË ÂÓ‰ÔÎÚÈÓÈ΋ ˘ÂÚ¤ÎÎÚÈÛË, Ë ÔÔ›· ÛÙ· ÎÔÚ›ÙÛÈ· ÂΉËÏÒÓÂÙ·È Û˘Ó‹ıˆ˜ ˆ˜ ÚÒÈÌË ‹‚Ë ÂÚÈÊÂÚÈ΋˜ ·ÈÙÈÔÏÔÁ›·˜. ∏ ÌÔÚȷ΋ ‚¿ÛË ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ MAS Â›Ó·È ÛËÌÂȷ΋ ۈ̷ÙÈ΋ ÌÂÙ·˙˘ÁˆÙÈ΋ ÌÂÙ¿ÏÏ·ÍË ÛÙÔ ÁÔÓ›‰ÈÔ Ô˘ Έ‰ÈÎÔÔÈ› ÙËÓ · ˘ÔÔÌ¿‰· Ù˘ ‰ÈÂÁÂÚÙÈ΋˜ Gs ÚˆÙ½Ó˘ (Gsa) Î·È ‚Ú›ÛÎÂÙ·È ÛÙÔ Ì·ÎÚ‡ ÛΤÏÔ˜ ÙÔ˘ ¯ÚˆÌÔÛÒÌ·ÙÔ˜ 20. ∏ ÎÏÈÓÈ΋ ÂÈÎfiÓ· οı ·ÙfiÌÔ˘ Ì MAS ÂÍ·ÚÙ¿Ù·È ·fi ÙË ‰È·ÛÔÚ¿ ÙˆÓ Î˘ÙÙ¿ÚˆÓ Ô˘ ʤÚÔ˘Ó ÙË ÌÂÙ¿ÏÏ·ÍË ÛÙÔ˘˜ ÚÔۂ‚ÏË̤ÓÔ˘˜ ÈÛÙÔ‡˜, ÚÔηÏÒÓÙ·˜ ¤Ó· ¢ڇ Ê¿ÛÌ· ÂÓ‰ÔÎÚÈÓÈÎÒÓ Î·È ÌË ÂÓ‰ÔÎÚÈÓÈÎÒÓ ÂΉËÏÒÛˆÓ. ¶ÂÚÈÁÚ¿ÊÔ˘Ì ÂÚ›ÙˆÛË MAS Û ÎÔÚ›ÙÛÈ Ô˘ ÂΉ‹ÏˆÛ ÂÚÈÊÂÚÈ΋ ÚÒÈÌË ‹‚Ë Û ËÏÈΛ· 14 ÌËÓÒÓ Î·È ·ÚÁfiÙÂÚ· ÈÓÒ‰Ë ‰˘ÛÏ·Û›· ÙˆÓ ÔÛÙÒÓ. √ ¤ÏÂÁ¯Ô˜ DNA ÙÔ˘ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜ ÁÈ· ÌÂÙ¿ÏÏ·ÍË ÛÙËÓ Gsa ·¤‚Ë ·ÚÓËÙÈÎfi˜. ∏ ·ÓÙ·fiÎÚÈÛË Ù˘ ·ÛıÂÓÔ‡˜ ÛÙË ıÂÚ·›· Ì ÏÂÙÚÔ˙fiÏË ‹Ù·Ó ·ÔÙÂÏÂÛÌ·ÙÈ΋. §¤ÍÂȘ ÎÏÂȉȿ: ™‡Ó‰ÚÔÌÔ McCune-Albright, ÂÚÈÊÂÚÈ΋ ÚÒÈÌË ‹‚Ë, ÈÓ҉˘ ‰˘ÛÏ·Û›· ÔÛÙÒÓ, Gs ÚˆÙ½ÓË, Gsa ÌÂÙ·ÏÏ¿ÍÂȘ.

1 ∞’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, “µÂÓÈ˙¤ÏÂÈÔ” °ÂÓÈÎfi ¡ÔÛÔÎÔÌ›Ô, ∏Ú¿ÎÏÂÈÔ ∫Ú‹Ù˘ 2 ∂Ó‰ÔÎÚÈÓÔÏÔÁÈÎfi ∆Ì‹Ì· ¡ÔÛÔÎÔÌ›Ԣ ¡›Î·È·˜ 3 ∂Ó‰ÔÎÚÈÓÔÏÔÁÈÎfi ∆Ì‹Ì· “µÂÓÈ˙¤ÏÂÈÔ” °ÂÓÈÎfi ¡ÔÛÔÎÔÌ›Ô, ∏Ú¿ÎÏÂÈÔ ∫Ú‹Ù˘ 4 ∂Ó‰ÔÎÚÈÓÔÏÔÁÈÎfi ∆Ì‹Ì· ¡ÔÛÔÎÔÌ›Ԣ ¶·›‰ˆÓ ∞ıËÓÒÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡” AÏÏËÏÔÁÚ·Ê›·: µ. ∞ÁÁÂÏ¿ÎÔ˘ vaagge3@yahoo.gr ∞’ ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋ “µÂÓÈ˙¤ÏÂÈÔ” °ÂÓÈÎfi ¡ÔÛÔÎÔÌ›Ô, ∏Ú¿ÎÏÂÈÔ ∫Ú‹Ù˘

McCune-Albright syndrome. A case report V. Aggelakou1, K. Anyfantakis2, K. Stamataki3, H. Kokori1, P. Papachileos4, C. Hadjiathanassiou† Abstract: The classical triad of the McCune-Albright syndrome (MAS) consists of bone fibrous dysplasia, skin hyperpigmentation (café-au-lait spots) and autonomous endocrine hyperfunction, frequently seen in females as peripheral precocious puberty. The molecular basis of MAS is postzygotic somatic missense mutation in the gene enconding the alpha subunit of the stimulatory Gs protein (Gsa), Ôn the long arm of chromosome 20. The clinical presentation of each individual is dependent of the particular distribution of cells carrying the mutation in the affected tissues, causing a broad spectrum of endocrine and nonendocrine manifestations. The case is reported of MAS in a girl with peripheral precocious puberty presenting at the age of 14 months, who subsequently developed bone fibrous dysplasia. Blood DNA analysis for Gsa mutation was negative. The patient responded well to letrozole treatment.

Key words: McCune-Albright syndrome, peripheral precocious puberty, bone fibrous dysplasia, Gs protein, Gsa mutations.

∂ÈÛ·ÁˆÁ‹ Œ¯Ô˘Ó ÂÚ¿ÛÂÈ ·ÎÚÈ‚Ò˜ 70 ¯ÚfiÓÈ· ·fi ÙfiÙ Ô˘ ÔÈ McCune Î·È Albright ÂÚȤÁÚ·„·Ó ÁÈ· ÚÒÙË ÊÔÚ¿ ÙÔ Û‡Ó‰ÚÔÌÔ McCune-Albright (MAS). ∆Ô MAS Â›Ó·È ÛÔÚ·‰È΋ Û¿ÓÈ· ÓfiÛÔ˜ Î·È ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ÙËÓ ÎÏ·ÛÈ΋ ÎÏÈÓÈ΋ ÙÚÈ¿‰·: ˘¤Ú¯ÚˆÛË ÙÔ˘ ‰¤ÚÌ·ÙÔ˜ (café-au-lait ÎËÏ›‰Â˜), ÔÏ˘ÔÛÙˆÙÈ΋ ÈÓÒ‰Ë ‰˘ÛÏ·Û›· ÙˆÓ ÔÛÙÒÓ (π¢√) Î·È ·˘ÙfiÓÔÌË ÂÓ‰ÔÎÚÈÓÈ΋ ˘ÂÚÏÂÈÙÔ˘ÚÁ›·, Ë ÔÔ›· ÂΉËÏÒÓÂÙ·È Î˘Ú›ˆ˜ ˆ˜ ÂÚÈÊÂÚÈ΋ ÚÒÈÌË ‹‚Ë (¶¶∏) ÛÙ· ÎÔÚ›ÙÛÈ·. H ‰È¿ÁÓˆÛË ÙÔ˘ MAS ıˆÚÂ›Ù·È ÙÂÎÌËÚȈ̤ÓË fiÙ·Ó ˘¿Ú¯Ô˘Ó ‰‡Ô ·fi Ù· ÛÙÔȯ›· Ù˘ ÎÏ·ÛÈ΋˜ ÎÏÈÓÈ΋˜ ÙÚÈ¿‰·˜. ∏ ·ÈÙÈÔÏÔÁ›· ÙÔ˘ MAS ¤ÁÈÓ ηٷÓÔËÙ‹ ÌÂÙ¿ ÙËÓ ·Ó·Î¿Ï˘„Ë ÙˆÓ G ÚˆÙÂ˚ÓÒÓ Î·È ÙÔ˘ ÚfiÏÔ˘ ÙÔ˘˜ ÛÙËÓ ÂÓ‰Ô΢ÙÙ¿ÚÈ· ÌÂÙ¿‰ÔÛË Û‹Ì·ÙÔ˜ ·fi ÙÔ˘˜ Gilman G Î·È Rodbell M ÙË ‰ÂηÂÙ›· ÙÔ˘ 1970 (¡fiÌÂÏ π·ÙÚÈ-

΋˜ 1994). ∆Ô 1986 Ô Happle R ‰È·Ù‡ˆÛ ÙËÓ ˘fiıÂÛË fiÙÈ ÙÔ MAS ÔÊ›ÏÂÙ·È Û ÌÂÙ·˙˘ÁˆÙÈ΋ ÌÂÙ¿ÏÏ·ÍË Û ·˘ÙÔۈ̷ÙÈÎfi ÂÈÎÚ·ÙÔ‡Ó ÁÔÓ›‰ÈÔ, Ë ÔÔ›· Û˘Ì‚·›ÓÂÈ Î·ı˘ÛÙÂÚË̤ӷ ηٿ ÙËÓ ÂÌ‚Ú˘ÔÁ¤ÓÂÛË, ÔfiÙ ԉËÁ› Û ηٿÛÙ·ÛË ÌˆÛ·˚ÎÈÛÌÔ‡ (1). ∆Ô 1991 Ô Weinstein ÂÓÙfiÈÛ ÛËÌÂȷΤ˜ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙÔ ÁÔÓ›‰ÈÔ Ù˘ · ˘ÔÔÌ¿‰·˜ Ù˘ ‰ÈÂÁÂÚÙÈ΋˜ Gs ÚˆÙ½Ó˘ (Gsa) Û ‰Â›ÁÌ·Ù· DNA ·fi ÚÔۂ‚ÏË̤ÓÔ˘˜ ÈÛÙÔ‡˜ ·ÛıÂÓÒÓ Ì MAS (2). ∏ ÌÔÚȷ΋ ‚¿ÛË ÙÔ˘ MAS ÂÚÈÁÚ¿ÊÂÙ·È ÛÙËÓ ∂ÈÎfiÓ· 1. ∏ ‚·Ú‡ÙËÙ· ÙˆÓ ÂΉËÏÒÛÂˆÓ ÙÔ˘ MAS Û˘Û¯ÂÙ›˙ÂÙ·È Ì ÙÔ ¯ÚfiÓÔ Ô˘ Û˘Ì‚·›ÓÔ˘Ó ÔÈ ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙË ‰È¿ÚÎÂÈ· Ù˘ ÂÌ‚Ú˘ÔÁ¤ÓÂÛ˘. ∏ ÚÒÈÌË ÂÌÊ¿ÓÈÛË ÌÂÙ·ÏÏ¿ÍÂˆÓ Â˘ı‡ÓÂÙ·È ÁÈ· ÙȘ ÈÔ ‚·ÚȤ˜ ÌÔÚʤ˜, ÂÓÒ Ë fi„ÈÌË ÂÌÊ¿ÓÈÛË ÌÂÙ¿ÏÏ·Í˘ Û ̛· ÌfiÓÔ Î˘ÙÙ·ÚÈ΋ ÛÂÈÚ¿ ÚÔηÏ› ÌÂÌÔӈ̤ӷ ˘ÂÚÏÂÈÙÔ˘ÚÁÔ‡ÓÙ· ·‰ÂÓÒÌ·Ù· (3). ÕÏϘ ÌË

1 1st Department of Paediatrics, “Venizeleio” General Hospital, Heraklion, Crete 2 Department of Endocrinology, Nikaia Hospital 3 Department of Endocrinology, “Venizeleio” General Hospital, Heraklion, Crete 4 Department of Endocrinology, “P. & A. Kyriakou” Children’s Hospital, Athens, Greece Correspondence: V. ∞ggelakou vaagge3@yahoo.gr 1st Department of Paediatrics, “Venizeleio” General Hospital, Heraklion, Crete, Greece

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µ. ∞ÁÁÂÏ¿ÎÔ˘ Î·È Û˘Ó.

Gs ÚˆÙ½ÓË A

OÚÌfiÓË OFF

‚Á · GDP

µ

‚Á ·

ÀÔ‰Ô¯¤·˜ Gs

∞‰ÂÓ˘Ï΢ÎÏ¿ÛË

E

G∆P

∞‰ÂÓ˘Ï΢ÎÏ¿ÛË

· ON

¢

‚Á · GTP

‚Á Pi

·

· ‚ Á ° GDP

GTP cAMP ATƒ ∞˘ÍË̤ÓË ÏÂÈÙÔ˘ÚÁ›· ΢ÙÙ¿ÚÔ˘-ÛÙfi¯Ô˘

GTP

∂ÈÎfiÓ· 1. ∏ ÌÔÚȷ΋ ‚¿ÛË ÙÔ˘ MAS. √È Gs ÚˆÙ½Ó˜ ÏÂÈÙÔ˘ÚÁÔ‡Ó ˆ˜ ‰È·ÎfiÙ˜. ∞. ™ÙËÓ ·ÓÂÓÂÚÁ‹ ηٿÛÙ·ÛË (OFF), Ë ‰ÈʈÛÊÔÚÈ΋ ÁÔ˘·ÓÔÛ›ÓË (GDP) Â›Ó·È Û˘Ó‰Â‰Â̤ÓË Ì ÙËÓ · ˘ÔÔÌ¿‰· Ù˘ Gs ÚˆÙ½Ó˘. µ. ŸÙ·Ó οÔÈÔ˜ Û˘Ó‰¤Ù˘ (ligand) (ÔÚÌfiÓË) ÚÔÛ‰Âı› ÛÙÔÓ ˘Ô‰Ô¯¤· ÙˆÓ Gs ÚˆÙÂ˚ÓÒÓ, ÚÔηÏÂ›Ù·È ·ÏÏ·Á‹ ÛÙË ‰ÔÌ‹ ÙÔ˘ ˘Ô‰Ô¯¤· Î·È ÛÙËÓ Gs ÚˆÙ½ÓË. ∏ · ˘ÔÔÌ¿‰· ·ÓÙ·ÏÏ¿ÛÛÂÈ ÙËÓ GDP Ì ÙÚÈʈÛÊÔÚÈ΋ ÁÔ˘·ÓÔÛ›ÓË (GTP) Î·È ÂÓÂÚÁÔÔÈ›ٷÈ. °. ™ÙËÓ ÂÓÂÚÁ‹ ηٿÛÙ·ÛË (√¡), ÙÔ ·-GTP ·ÔÎfiÙÂÙ·È ·fi ÙȘ ‚ Î·È Á ˘ÔÔÌ¿‰Â˜ Î·È Ú˘ıÌ›˙ÂÈ ÔÏϤ˜ ÏÂÈÙÔ˘ÚÁ›Â˜ ÙÔ˘ ΢ÙÙ¿ÚÔ˘, ̤ۈ Ù˘ ÂÓÂÚÁÔÔ›ËÛ˘ Ù˘ ·‰ÂÓ˘Ï΢ÎÏ¿Û˘ Î·È Ù˘ ·‡ÍËÛ˘ ÙÔ˘ cAMP. ¢. To GTP ˘‰ÚÔχÂÙ·È Ì¤Ûˆ Ù˘ ÂÓ‰ÔÁÂÓÔ‡˜ GTP-¿Û˘ Ù˘ · ˘ÔÔÌ¿‰·˜ Î·È ÙÔ ÌfiÚÈÔ ·-GDP Â·Ó·Û˘Ó‰¤ÂÙ·È Ì ÙȘ ‚ Î·È Á ˘ÔÔÌ¿‰Â˜ Î·È Ë ÂÙÂÚÔÙÚÈÌÂÚ‹˜ Gs ÚˆÙ½ÓË Â›Ó·È ¤ÙÔÈÌË ÁÈ· ¿ÏÏÔ Î‡ÎÏÔ ÂÓÂÚÁÔÔ›ËÛ˘. ∂. ™ÙÔ MAS Ë ÌÂÙ¿ÏÏ·ÍË Ù˘ Gs· ˘ÔÔÌ¿‰·˜ ¢ڛÛÎÂÙ·È ÛÙË ı¤ÛË ÙÔ˘ ÌÔÚ›Ô˘ Ô˘ ¤¯ÂÈ ÙË ‰Ú¿ÛË Ù˘ GTP-¿Û˘. ∏ ˘‰ÚfiÏ˘ÛË Ù˘ GTP Û GDP ‰ÂÓ Ú·ÁÌ·ÙÔÔÈÂ›Ù·È Î·È ÙÔ Î‡Îψ̷ Â›Ó·È ‰È·ÚÎÒ˜ Û ηٿÛÙ·ÛË √¡ ¯ˆÚ›˜ ÙËÓ ·ÚÔ˘Û›· Û˘Ó‰¤ÙË (ligand) (ÔÚÌfiÓ˘), Ì ·ÔÙ¤ÏÂÛÌ· ÙÔÓ ·˘ÙfiÓÔÌÔ ·˘ÍË̤ÓÔ ÌÂÙ·‚ÔÏÈÛÌfi ÙÔ˘ ΢ÙÙ¿ÚÔ˘-ÛÙfi¯Ô˘.

ÂÓ‰ÔÎÚÈÓÈΤ˜ ÂΉËÏÒÛÂȘ ÙÔ˘ MAS Â›Ó·È ÚÔÛ‚ÔÏ‹ ÙÔ˘ ‹·ÙÔ˜ Î·È ÙˆÓ ¯ÔÏËÊfiÚˆÓ, ÚÔÛ‚ÔÏ‹ ÙÔ˘ Ì˘Ôηډ›Ô˘ Ì ÔÈΛϘ ÂΉËÏÒÛÂȘ Î·È ÓÂÊÚÈ΋ ·ÒÏÂÈ· ʈÛÊfiÚÔ˘ (4,5,6).

¶ÂÚÈÁÚ·Ê‹ ÂÚ›ÙˆÛ˘ ∏ ·ÛıÂÓ‹˜ ÚÔÛÎÔÌ›ÛıËΠÁÈ· ÚÒÙË ÊÔÚ¿ ÛÙËÓ ÎÏÈÓÈ΋ Ì·˜ Û ËÏÈΛ· 14 ÌËÓÒÓ Ì ÎÔÏÈ΋ ·ÈÌfiÚÚÔÈ· Î·È ‰ÈfiÁΈÛË Ì·˙ÈÎÒÓ ·‰¤ÓˆÓ. ∂›Ó·È ÙÔ ÚÒÙÔ ·È‰› ˘ÁÈÒÓ ÁÔÓ¤ˆÓ Ô˘ ÁÂÓÓ‹ıËΠ‡ÛÙÂÚ· ·fi Ê˘ÛÈÔÏÔÁÈ΋ ÙÂÏÂÈfiÌËÓË Î‡ËÛË ÌÂ Ê˘ÛÈÔÏÔÁÈÎfi ÙÔÎÂÙfi Î·È ¯·ÌËÏfi ‚¿ÚÔ˜ Á¤ÓÓËÛ˘ 1.980 g. ¢ÂÓ ·Ó·Ê¤ÚÔÓÙ·È ÂÚÈÁÂÓÓËÙÈο ÚÔ‚Ï‹Ì·Ù·. ∏ „˘¯ÔÎÈÓËÙÈ΋ ÂͤÏÈÍË ‹Ù·Ó ÔÌ·Ï‹. ™ÙËÓ ·ÓÙÈÎÂÈÌÂÓÈ΋ ÂͤٷÛË, ·ÚÔ˘Û›·˙ ·‡ÍËÛË ÙÔ˘ ÌÂÁ¤ıÔ˘˜ ÙˆÓ Ì·˙ÈÎÒÓ ·‰¤ÓˆÓ (ÛÙ¿‰ÈÔ ππ ηٿ Tanner), ÎÔÏÈ΋ ·ÈÌfiÚÚÔÈ· Î·È ˘ÂÚÙÚÔÊ›· ÙˆÓ ÌÈÎÚÒÓ ¯ÂÈϤˆÓ ÙÔ˘ ·È‰Ô›Ô˘ (∂ÈÎfiÓ· 2). H ÙÚ›¯ˆÛË ÙÔ˘ ÂÊË‚·›Ô˘ Î·È Ù˘ Ì·Û¯¿Ï˘ ‹Ù·Ó ÛÙ·‰›Ô˘ π ηٿ Tanner. À‹Ú¯Â Ì›· ÌÂÏ·¯ÚˆÌ·ÙÈ΋ ÎËÏ›‰· ÛÙÔÓ ·ÚÈÛÙÂÚfi ÌËÚfi ‰È·Ì¤ÙÚÔ˘ 2 cm Ì ÔÌ·Ï‹ ·Ú˘Ê‹. ∞fi Ù· ÏÔÈ¿ Û˘ÛÙ‹Ì·Ù· ‰ÂÓ ·ÚÔ˘Û›·˙ ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ∏ ·ÚÙËÚȷ΋ ›ÂÛË ‹Ù·Ó 95/77 mm Hg. ∆Ô Ì‹ÎÔ˜ ÛÒÌ·ÙÔ˜ ‹Ù·Ó 80 cm (90Ë ∂.£.), ÙÔ ‚¿ÚÔ˜ ÛÒÌ·ÙÔ˜ 8.250 g (3Ë ∂.£.) Î·È Ë ÂÚ›ÌÂÙÚÔ˜ ÎÂÊ·Ï‹˜ 44 cm (3Ë ∂.£.). ∆Ô ‡„Ô˜ Ù˘ ÌËÙ¤Ú·˜ Â›Ó·È 146,4 cm, ÙÔ ‡„Ô˜ ÙÔ˘ ·Ù¤Ú· 171,7 cm Î·È ÙÔ ˘ÔÏÔÁÈ˙fiÌÂÓÔ ÙÂÏÈÎfi ‡„Ô˜-ÛÙfi¯Ô˜ Ù˘ ·ÛıÂÓÔ‡˜ (target height) Â›Ó·È 153 cm.

Paediatriki 2008;71:317-322

∆· ·ÔÙÂϤÛÌ·Ù· ÙÔ˘ ‚·ÛÈÎÔ‡ ÂÚÁ·ÛÙËÚÈ·ÎÔ‡ ÂϤÁ¯Ô˘ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈο. ŒÁÈÓ Ï‹Ú˘ ÂÚÁ·ÛÙËÚÈ·Îfi˜ ¤ÏÂÁ¯Ô˜ ÛÙ· Ï·›ÛÈ· Ù˘ ‰È·ÊÔÚÈ΋˜ ‰È¿ÁÓˆÛ˘ Ù˘ ÚÒÈÌ˘ ‹‚˘. √È ÙÈ̤˜ ÙˆÓ FT3, FT4, TSH, 17-OH ÚÔÁÂÛÙÂÚfiÓ˘, ‰Â¸‰ÚÔÂÈ·Ó‰ÚÔÛÙÂÚfiÓ˘, ¢4 ·Ó‰ÚÔÛÙÂÓ‰ÈfiÓ˘, F-ÙÂÛÙÔÛÙÂÚfiÓ˘, ACTH, ÎÔÚÙÈ˙fiÏ˘, ‚-¯ÔÚȷ΋˜ ÁÔÓ·‰ÔÙÚÔÊ›Ó˘, ÚÔÏ·ÎÙ›Ó˘, ÈÓÛÔ˘ÏÈÓfiÌÔÚÊÔ˘ ·Ú¿ÁÔÓÙ· 1 (IGF-1), ·Ú·ıÔÚÌfiÓ˘, ·-ÂÌ‚Ú˘˚΋˜ ÚˆÙ½Ó˘, ηÚÎÈÓÔÂÌ‚Ú˘˚ÎÔ‡ ·ÓÙÈÁfiÓÔ˘ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈΤ˜. ŸÌˆ˜ Ë ÙÈÌ‹ Ù˘ ÔÈÛÙÚ·‰ÈfiÏ˘ ‹Ù·Ó ˘„ËÏ‹ (211 pmol/L Ì Ê.Ù. <25 pmol/L), ÂÓÒ ˘‹Ú¯Â ηٷÛÙÔÏ‹ Ù˘ ¤ÎÎÚÈÛ˘ ÙˆÓ FSH Î·È LH Ì ÙÈ̤˜ <0,001 mUI/ml (Ê.Ù. 0,11-1,8

∂ÈÎfiÓ· 2. ∏ ÂÈÎfiÓ· Ù˘ ·ÛıÂÓÔ‡˜ ηٿ ÙËÓ ÂÈÛ·ÁˆÁ‹ Ù˘.

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™‡Ó‰ÚÔÌÔ McCune-Albright

ÚfiÛıÈ· fi„Ë

Ô›ÛıÈ· fi„Ë

∂ÈÎfiÓ· 4. ™ÈÓıËÚÔÁÚ¿ÊËÌ· ÔÛÙÒÓ Û ËÏÈΛ· 5 ó ¯ÚfiÓˆÓ.

∂ÈÎfiÓ· 3. √ÛÙÂÔÏ˘ÙÈ΋ ‚Ï¿‚Ë ÛÙËÓ ÂÚÈÔ¯‹ ÙÔ˘ ·˘¯¤Ó· ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ ÌËÚÈ·›Ô˘ ÔÛÙÔ‡.

mUI/ml) Î·È <0,12 mUI/ml (Ê.Ù. 0,7-3,2 mUI/ml), ·ÓÙ›ÛÙÔȯ·. ∏ ·¿ÓÙËÛË ÛÙË ‰˘Ó·ÌÈ΋ ‰ÔÎÈÌ·Û›· Ì ¯ÔÚ‹ÁËÛË ˘Ôı·Ï·ÌÈÎÔ‡ ·Ú¿ÁÔÓÙ· ¤ÎÎÚÈÛ˘ ÙˆÓ ÁÔÓ·‰ÔÙÚÔÊÈÓÒÓ (GnRH) ‹Ù·Ó ÚÔÂÊË‚ÈÎÔ‡ Ù‡Ô˘. ∆Ô ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ¤Ûˆ ÁÂÓÓËÙÈÎÒÓ ÔÚÁ¿ÓˆÓ ¤‰ÂÈÍ ·‡ÍËÛË ÙÔ˘ ÌÂÁ¤ıÔ˘˜ Ù˘ Ì‹ÙÚ·˜ (3,4x1,6 cm) Î·È ·‡ÍËÛË ÙÔ˘ ¿¯Ô˘˜ ÙÔ˘ ÂÓ‰ÔÌËÙÚ›Ô˘, ηıÒ˜ Î·È Î‡ÛÙÂȘ ÛÙËÓ ·ÚÈÛÙÂÚ‹ Î·È ‰ÂÍÈ¿ ˆÔı‹ÎË ‰È·Ì¤ÙÚÔ˘ 2,7 cm Î·È 0,7 cm, ·ÓÙ›ÛÙÔȯ·. ∏ ÔÛÙÈ΋ ËÏÈΛ· Ù˘ ·ÛıÂÓÔ‡˜ ‹Ù·Ó 3 ÂÙÒÓ. ∏ ‰˘Ó·ÌÈ΋ ‰ÔÎÈÌ·Û›· ·Ó·ÛÙÔÏ‹˜ Ù˘ ¤ÎÎÚÈÛ˘ Ù˘ ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ Ì ¯ÔÚ‹ÁËÛË ÁÏ˘Îfi˙˘ ·fi ÙÔ ÛÙfiÌ· (OGTT), Ë Ì·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· ˘fiÊ˘Û˘ Î·È ÙÔ ˘ÂÚ˯ÔÁÚ¿ÊËÌ· ÂÈÓÂÊÚȉ›ˆÓ ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈο. √È ·ÎÙÈÓÔÁڷʛ˜ Ì·ÎÚÒÓ ÔÛÙÒÓ Î·È ÎÚ·Ó›Ô˘ Î·È ÙÔ Tc99m-MDP ÛÈÓıËÚÔÁÚ¿ÊËÌ· ÔÛÙÒÓ ‰ÂÓ Â›¯·Ó ·ıÔÏÔÁÈο Â˘Ú‹Ì·Ù·. ªÂ Ù· ·Ú·¿Óˆ Â˘Ú‹Ì·Ù·, Ù¤ıËÎÂ Ë ‰È¿ÁÓˆÛË Ù˘ ¶¶∏, ÏfiÁˆ ·˘ÙfiÓÔÌ˘ ˘ÂÚ¤ÎÎÚÈÛ˘ ÔÈÛÙÚÔÁfiÓˆÓ ·fi ÙȘ ˆÔıËÎÈΤ˜ ·ÛÙÂȘ. ∏ ÎÔÏÈ΋ ·ÈÌfiÚÚÔÈ· ˘Ô¯ÒÚËÛÂ. ™Â Â·ÓÂͤٷÛË ‡ÛÙÂÚ· ·fi 3 ‚‰ÔÌ¿‰Â˜, ÔÈ Ì·˙ÈÎÔ› ·‰¤Ó˜ Î·È ÙÔ Ì¤ÁÂıÔ˜ ÙˆÓ ÌÈÎÚÒÓ ¯ÂÈϤˆÓ ›¯·Ó ˘ÔÛÙÚ·Ê›. ∞ÎÔÏÔ‡ıËÛ·Ó ¿ÏÏ· ‰‡Ô ÂÂÈÛfi‰È· ÎÔÏÈ΋˜ ·ÈÌfiÚÚÔÈ·˜ Ì ٷ ›‰È· Û˘ÓÔ‰¿ Â˘Ú‹Ì·Ù· 2 Î·È 4 Ì‹Ó˜ ÌÂÙ¿ ÙÔ ÚÒÙÔ ÂÂÈÛfi‰ÈÔ. ™ÙÔ ÙÂÏÂ˘Ù·›Ô ÂÂÈÛfi‰ÈÔ ·ÔÊ·Û›ÛÙËΠӷ ·Ú¯›ÛÂÈ ıÂÚ·›· Ì ÙÔÓ Ì·ÎÚ¿˜ ‰Ú¿Û˘ ·Ó·ÛÙÔϤ· Ù˘ ·ÚˆÌ·Ù¿Û˘ 3˘ ÁÂÓÈ¿˜ ÏÂÙÚÔ˙fiÏË Ì ‰fiÛË 1,5 mg/m2 ÂÈÊ¿ÓÂÈ·˜ ÛÒÌ·ÙÔ˜ ËÌÂÚËÛ›ˆ˜ Î·È ÛÈÚÔÓÔÏ·ÎÙfiÓË 10 mg/̤ڷ ÁÈ· Ó· ·Ó·ÛÙ·Ï› Ë Û‡ÓıÂÛË ÙˆÓ ÔÈÛÙÚÔÁfiÓˆÓ. ∏ ·ÛıÂÓ‹˜ ¤ÎÙÔÙ ‰ÂÓ ·ÚÔ˘Û›·ÛÂ Ó¤Ô ÂÂÈÛfi‰ÈÔ ÎÔÏÈ΋˜ ·ÈÌfiÚÚÔÈ·˜. √ Â·Ó·ÏË-

ÙÈÎfi˜ ·ÎÙÈÓÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜ Û ËÏÈΛ· 34 ÌËÓÒÓ ¤‰ÂÈÍ ÔÛÙÂÔÏ˘ÙÈ΋ ‚Ï¿‚Ë ÛÙÔÓ ·˘¯¤Ó· ÙÔ˘ ·ÚÈÛÙÂÚÔ‡ ÌËÚÈ·›Ô˘ (∂ÈÎfiÓ· 3). √ Û˘Ó‰˘·ÛÌfi˜ Ù˘ ¶¶∏ Î·È ÙˆÓ ·ıÔÏÔÁÈÎÒÓ Â˘ÚËÌ¿ÙˆÓ ·fi Ù· ÔÛÙ¿ ¤ıÂÛ·Ó ÙË ‰È¿ÁÓˆÛË ÙÔ˘ MAS ÛÙËÓ ·ÛıÂÓ‹. √ ÁÔÓȉȷÎfi˜ ¤ÏÂÁ¯Ô˜ ÁÈ· ÌÂÙ¿ÏÏ·ÍË ÛÙËÓ Gsa Û ‰Â›ÁÌ· DNA ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜ ‹Ù·Ó ·ÚÓËÙÈÎfi˜. ™Â ÚfiÛÊ·ÙÔ Â·Ó¤ÏÂÁ¯Ô Ù˘ ·ÛıÂÓÔ‡˜ Û ËÏÈΛ· 5,5 ¯ÚfiÓˆÓ ‰ÂÓ ·Ó¢ڤıËÛ·Ó Î‡ÛÙÂȘ ÛÙȘ ˆÔı‹Î˜, Ë ÔÈÛÙÚ·‰ÈfiÏË ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈ΋, Ë ÔÛÙÈ΋ ËÏÈΛ· ‹Ù·Ó 6,5 ¯ÚfiÓˆÓ, ·ÏÏ¿ ÛÙÔ Tc-99m-MDP ÛÈÓıËÚÔÁÚ¿ÊËÌ· ÔÛÙÒÓ ·Ú·ÙËÚÂ›Ù·È ·˘ÍË̤ÓË Î·ı‹ÏˆÛË ÙÔ˘ Ú·‰ÈÔÊ·ÚÌ¿ÎÔ˘ ÛÙÔ ·ÚÈÛÙÂÚfi Ï·ÁfiÓÈÔ, ÛÙËÓ ÂÚÈÔ¯‹ ÙˆÓ ÙÚÔ¯·ÓÙ‹ÚˆÓ ÙÔ˘ Û˘ÛÙÔ›¯Ô˘ ÌËÚÈ·›Ô˘ Î·È ÛÙËÓ ·ÚÈÛÙÂÚ‹ ÈÂÚÔÏ·ÁfiÓÈÔ ¿ÚıÚˆÛË (∂ÈÎfiÓ· 4). ∏ ·ÛıÂÓ‹˜ ‰ÂÓ ·ÚÔ˘ÛÈ¿˙ÂÈ Û˘ÌÙÒÌ·Ù· ·fi Ù· ÔÛÙ¿. ŒÁÈÓ ¤ÏÂÁ¯Ô˜ ÁÈ· ·ÒÏÂÈ· ʈÛÊfiÚÔ˘ ·fi ÙÔ˘˜ ÓÂÊÚÔ‡˜. √ ʈÛÊfiÚÔ˜ ÔÚÔ‡ Î·È Ô‡ÚˆÓ 24ÒÚÔ˘, ηıÒ˜ Î·È ÙÔ ËÏ›ÎÔ ÊˆÛÊfiÚÔ˜/ÎÚ·ÙÈÓ›ÓË ‹Ù·Ó Ê˘ÛÈÔÏÔÁÈο. ∏ ıÂÚ·›· Û˘Ó¯›˙ÂÙ·È Ì ÏÂÙÚÔ˙fiÏË Î·È Ë ·ÛıÂÓ‹˜ ·Ú·ÎÔÏÔ˘ıÂ›Ù·È Î·Ù¿ Ù·ÎÙ¿ ‰È·ÛÙ‹Ì·Ù·.

™˘˙‹ÙËÛË ∆Ô MAS Â›Ó·È ÂÙÂÚÔÁÂÓ‹˜, ÂÍÂÏÈÛÛfiÌÂÓË ÓfiÛÔ˜ Î·È Û¿ÓÈ· ÂÌÊ·Ó›˙ÂÙ·È ·fi Ù· ·Ú¯Èο ÛÙ¿‰È· Ì ÙËÓ ÎÏ·ÛÈ΋ ÎÏÈÓÈ΋ ÙÚÈ¿‰·. ™˘Ó‹ıˆ˜ ˘¿Ú¯ÂÈ ˘Ô„›· ÙÔ˘ MAS, ÏfiÁˆ Ù˘ ·ÚÔ˘Û›·˜ ÌÔÓˆÌ¤ÓˆÓ Â˘ÚËÌ¿ÙˆÓ, fiˆ˜ ÔÈ ¯·Ú·ÎÙËÚÈÛÙÈΤ˜ ÌÂÏ·¯ÚˆÌ·ÙÈΤ˜ (café-au-lait) ÎËÏ›‰Â˜ ÙÔ˘ ‰¤ÚÌ·ÙÔ˜, Ë ÈÓ҉˘ ‰˘ÛÏ·Û›· ÙˆÓ ÔÛÙÒÓ Î·È Ë ·ÓÂÍ¿ÚÙËÙË ·fi ÙȘ ÁÔÓ·‰ÔÙÚÔʛӘ ÚÒÈÌË ‹‚Ë, ÂÓÒ ÌÔÚ› Ó· ÌÂÛÔÏ·‚‹ÛÔ˘Ó ·ÚÎÂÙ¿ ¯ÚfiÓÈ· ̤¯ÚÈ ÙËÓ ÂÌÊ¿ÓÈÛË Ù˘ ÔÏÔÎÏËڈ̤Ó˘ ÌÔÚÊ‹˜ ÙÔ˘ MAS (3). ∏ ·ÛıÂÓ‹˜ Ì·˜ ÚÔÛ‹Ïı ·Ú¯Èο ÌfiÓÔ Ì ÎÏÈÓÈο Â˘Ú‹Ì·Ù· ¶¶∏. ∏ ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË Ù˘ ¶¶∏ ÂÚÈÂÏ¿Ì‚·Ó ΢ڛˆ˜ ÙËÓ Â͈ÁÂÓ‹ Ï‹„Ë ÔÈÛÙÚÔÁfiÓˆÓ, ÙÔ˘˜ fiÁÎÔ˘˜ ÙˆÓ ˆÔıËÎÒÓ ·fi ·ÙÙ·Ú· Ù˘ ÎÔÎÎÒ‰Ô˘˜ ¶·È‰È·ÙÚÈ΋ 2008;71:317-322

Pediatri Jul-Aug 08

30-07-08

15:53

™ÂÏ›‰·320

320

µ. ∞ÁÁÂÏ¿ÎÔ˘ Î·È Û˘Ó.

¶›Ó·Î·˜ 1. ∫ÏÈÓÈο Â˘Ú‹Ì·Ù· Û ·ÛıÂÓ›˜ Ì MAS Û ÙÚÂȘ ÌÂÁ¿Ï˜ ÌÂϤÙ˜ Albers N et al. (2002) Lumbroso et al. (2004) Ringel et al. (1996) (5) ¶·ÚÔ‡Û· German study (6) European collaborative study (4) ¶ÂÚÈÁÚ·Ê‹ ™‡ÓÔÏÔ ·ÛıÂÓÒÓ (Á˘Ó·›Î˜/¿Ó‰Ú˜) πÓ҉˘ ‰˘ÛÏ·Û›· ÔÛÙÒÓ Café-au-lait ÎËÏ›‰Â˜ ¶ÂÚÈÊÂÚÈ΋ ÚÒÈÌË ‹‚Ë ÀÂÚ¤ÎÎÚÈÛË ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ ÀÂÚÎÔÚÙÈ˙ÔÏ·ÈÌ›· ÀÂÚÚÔÏ·ÎÙÈÓ·ÈÌ›· ÀÂÚı˘ÚÂÔÂȉÈÛÌfi˜ ÀÂÚ·Ú·ı˘ÚÂÔÂȉÈÛÌfi˜ ∏·ÙÈ΋ ÓfiÛÔ˜ ∫·Ú‰È·Î‹ ÓfiÛÔ˜ ƒ·¯›Ùȉ·/ÔÛÙÂÔ̷ϷΛ·

41 36/5 32 (78%) 35 (85%) 37 (90%) 3 (7%) 1 (2,5%) 1 (2,5%) 5 (12%) 5 (12%) 4 (10%)

ÛÙÈ‚¿‰·˜ ‹ Ù˘ ı‹Î˘, ÙÔ˘˜ fiÁÎÔ˘˜ Ô˘ ·Ú¿ÁÔ˘Ó ¯ÔÚȷ΋ ÁÔÓ·‰ÔÙÚÔÊ›ÓË Î·È ÙÔ Û‡Ó‰ÚÔÌÔ McCuneAlbright. ∏ ÂÌÊ¿ÓÈÛË Ù˘ ÈÓÒ‰Ô˘˜ ‰˘ÛÏ·Û›·˜ ÙˆÓ ÔÛÙÒÓ ÌÂÚÈÎÔ‡˜ Ì‹Ó˜ ·ÚÁfiÙÂÚ· ¤ıÂÛ ÙË ‰È¿ÁÓˆÛË ÙÔ˘ MAS. ™ÙÔÓ ¶›Ó·Î· 1 ·ÚÔ˘ÛÈ¿˙ÂÙ·È Ë Û˘¯ÓfiÙËÙ· ÂÌÊ¿ÓÈÛ˘ ÙˆÓ Â˘ÚËÌ¿ÙˆÓ ÙÔ˘ MAS Û ÙÚÂȘ ÌÂÁ¿Ï˜ ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ (4,5,6). ∏ ÂÚÈÊÂÚÈ΋ ÚÒÈÌË ‹‚Ë (¶¶∏) Â›Ó·È Ë Û˘¯ÓfiÙÂÚË ÂÓ‰ÔÎÚÈÓÈ΋ ÂΉ‹ÏˆÛË ÙÔ˘ MAS. ¶ÚÔÛ‚¿ÏÏÂÈ Î˘Ú›ˆ˜ ÎÔÚ›ÙÛÈ· (64-79%) Î·È Û·ÓÈfiÙÂÚ· ·ÁfiÚÈ· (15%) (4,5,6). ∏ ÚÒÈÌË ‹‚Ë ÛÙ· ÎÔÚ›ÙÛÈ· Ì MAS ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ·˘ÙfiÓÔÌË ˆÔıËÎÈ΋ ÏÂÈÙÔ˘ÚÁ›· Î·È Ù˘Èο ÂΉËÏÒÓÂÙ·È ÚÈÓ ·fi ÙËÓ ËÏÈΛ· ÙˆÓ 4 ¯ÚfiÓˆÓ (2,8±2,3 ¯ÚfiÓÈ·) (7). ∏ ·Ó¿Ù˘ÍË ÌÂÁ¿ÏˆÓ ÏÂÈÙÔ˘ÚÁÈÎÒÓ ˆÔıËÎÈÎÒÓ Î‡ÛÙÂˆÓ Ô‰ËÁ› Û ·˘ÍË̤ÓË ·Ú·ÁˆÁ‹ ÔÈÛÙÚ·‰ÈfiÏ˘, ÂÓÒ ÔÈ ÁÔÓ·‰ÔÙÚÔʛӘ ·Ú·Ì¤ÓÔ˘Ó ¯·ÌËϤ˜ ‹ Î·È Î·ÙÂÛÙ·Ï̤Ó˜ (8). ∞ÔÙ¤ÏÂÛÌ· Ù˘ ÔÈÛÙÚÔÁÔÓ·ÈÌ›·˜ Â›Ó·È Ë ·Ó¿Ù˘ÍË ÙˆÓ Ì·ÛÙÒÓ, Ë ˘ÂÚÙÚÔÊ›· ÙˆÓ ÌÈÎÚÒÓ ¯ÂÈϤˆÓ ÙÔ˘ ·È‰Ô›Ô˘, ηıÒ˜ Î·È Ë ·‡ÍËÛË ÙÔ˘ ÌÂÁ¤ıÔ˘˜ Ù˘ Ì‹ÙÚ·˜ Î·È ÙˆÓ ˆÔıËÎÒÓ. ∏ ÂÌÊ¿ÓÈÛË ÎÔÏÈ΋˜ ·ÈÌfiÚÚÔÈ·˜ Â›Ó·È ÙÔ ·ÔÙ¤ÏÂÛÌ· Ù˘ ÙÒÛ˘ ÙˆÓ ÂÈ¤‰ˆÓ ÙˆÓ ÔÈÛÙÚÔÁfiÓˆÓ fiÙ·Ó Ë ˆÔıËÎÈ΋ ·ÛÙË ˘ÔÛÙÚ¤ÊÂÙ·È (8). ∏ ˘ÂÚ¤ÎÎÚÈÛË ÔÈÛÙÚÔÁfiÓˆÓ ÚÔηÏ› ÂÈÙ¿¯˘ÓÛË Ù˘ ÔÛÙÈ΋˜ ËÏÈΛ·˜ Î·È ÌÔÚ› Ó· Ô‰ËÁ‹ÛÂÈ Û ¯·ÌËÏfi ÙÂÏÈÎfi ·Ó¿ÛÙËÌ·. ∏ ÓfiÛÔ˜ ·ÎÔÏÔ˘ı› ·Úfi‚ÏÂÙË ÔÚ›· Ì ÂÌÊ¿ÓÈÛË Î·È ˘Ô¯ÒÚËÛË ÛËÌ›ˆÓ ÛÂÍÔ˘·ÏÈ΋˜ ˆÚ›Ì·ÓÛ˘, Ë ÔÔ›· ¤¯ÂÈ Û¯¤ÛË Ì ٷ Â›‰· ÙˆÓ ÔÈÛÙÚÔÁfiÓˆÓ Ô˘ ·Ú¿ÁÔÓÙ·È ·fi ÙȘ ˆÔı‹Î˜. √È ˆÔıËÎÈΤ˜ ·ÛÙÂȘ ÂÌÊ·Ó›˙ÔÓÙ·È Û˘Ó‹ıˆ˜ ·Ó¿ 1 ‹ 2 Ì‹Ó˜, ·ÏÏ¿ ÌÔÚ› Ó· ˘¿ÚÍÔ˘Ó ÌÂÁ¿Ï· ‰È·ÛÙ‹Ì·Ù· ·˘ÙfiÌ·Ù˘ ˘Ô¯ÒÚËÛ‹˜ ÙÔ˘˜ (8). ŸÙ·Ó Ë ÔÛÙÈ΋ ËÏÈΛ· ÂÁÁ›˙ÂÈ Ù· 12 ¯ÚfiÓÈ· Â›Ó·È Èı·ÓfiÓ Ó· ÚÔ·„ÂÈ ·ÏËı‹˜ ÎÂÓÙÚÈ΋ ‹‚Ë. ∏ Ê˘ÛÈ΋ ÔÚ›· Ù˘ ·˘ÙfiÓÔÌ˘ ˘ÂPaediatriki 2008;71:317-322

113 98/15 52 (46%) 60 (53%) 89 (79%) 5 (4,5%) 7 (6%) 4 (3,5%) 3 (2,5%) 1 (0,8%) 6 (5,5%) -

158 105/53 154 (97,5%) 135 (85,5%) 82 (52%) 42 (26,5%) 9 (5,5%) 23 (14,5%) 30 (19%) 16 (10%) 17 (11%) 4 (2,5%)

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Ú¤ÎÎÚÈÛ˘ ÔÈÛÙÚÔÁfiÓˆÓ ‰ÂÓ Â›Ó·È ÁÓˆÛÙ‹, ÏfiÁˆ Ù˘ Û·ÓÈfiÙËÙ·˜ Ù˘ ÓfiÛÔ˘. ™Â ÌÂϤÙË ÙˆÓ Matarazzo Î·È Û˘Ó., Ë ·˘ÙÔÓÔÌ›· ÙˆÓ ˆÔıËÎÒÓ Û˘Ó¯›˙ÂÙ·È Û οÔȘ ÂÚÈÙÒÛÂȘ ÂÊ‹‚ˆÓ Î·È Ó·ÚÒÓ Á˘Ó·ÈÎÒÓ Ì MAS (9). º·›ÓÂÙ·È fiÙÈ fiÙ·Ó Ë ¶¶∏ ÂÌÊ·ÓÈÛÙ› ÓˆÚ›˜ Î·È Ì ÛÔ‚·Ú¤˜ ÂΉËÏÒÛÂȘ, ·˘Í¿ÓÂÈ ÙËÓ Èı·ÓfiÙËÙ· Ó· Û˘Ó¯ÈÛı› Ë ·˘ÙfiÓÔÌË ÏÂÈÙÔ˘ÚÁ›· ÙˆÓ ˆÔıËÎÒÓ Û ÌÂÁ·Ï‡ÙÂÚË ËÏÈΛ· (9). ∏ ıÂÚ·¢ÙÈ΋ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ¶¶∏ Â›Ó·È Ôχ ÛËÌ·ÓÙÈ΋ ÁÈ· Ó· ·ÔÙÚ·› ÙÔ ÂӉ¯fiÌÂÓÔ ÙÔ˘ ÎÔÓÙÔ‡ ÙÂÏÈÎÔ‡ ·Ó·ÛÙ‹Ì·ÙÔ˜. Œ¯Ô˘Ó ‰ÔÎÈÌ·Ûı› ·ÚÎÂÙ¤˜ Ê·Ú̷΢ÙÈΤ˜ Ô˘Û›Â˜, ÔÈ Ôԛ˜ ›Ù ·Ó·ÛÙ¤ÏÏÔ˘Ó ÙË Û‡ÓıÂÛË ÙˆÓ ÔÈÛÙÚÔÁfiÓˆÓ, ̤ۈ ·Ó·ÛÙÔÏ‹˜ Ù˘ ·ÚˆÌ·Ù¿Û˘, ›Ù ÂÎÏÂÎÙÈο ·Ó·ÛÙ¤ÏÏÔ˘Ó ÙÔ˘˜ ˘ԉԯ›˜ ÙˆÓ ÔÈÛÙÚÔÁfiÓˆÓ ÛÙËÓ ÂÚÈʤÚÂÈ·. √È ÚÒÙ˘ ÁÂÓÈ¿˜ ·Ó·ÛÙÔÏ›˜ Ù˘ ·ÚˆÌ·Ù¿Û˘, fiˆ˜ Ë ÙÂÛÙÔÏ·ÎÙfiÓË, ‰ÂÓ ¯ÚËÛÈÌÔÔÈÔ‡ÓÙ·È ϤÔÓ ÛÙ· ÎÔÚ›ÙÛÈ· Ì ¶¶∏ (10). ∞fi ÙÔ˘˜ ·Ó·ÛÙÔÏ›˜ Ù˘ ·ÚˆÌ·Ù¿Û˘ 3˘ ÁÂÓÈ¿˜, Ë ÏÂÙÚÔ˙fiÏË ¤¯ÂÈ ‰ÒÛÂÈ ·ÚÎÂÙ¿ ηϿ ·ÔÙÂϤÛÌ·Ù· Ô˘ ·ÊÔÚÔ‡Ó Î·È ÙËÓ ÂÈ‚Ú¿‰˘ÓÛË Ù˘ ÔÛÙÈ΋˜ ˆÚ›Ì·ÓÛ˘ Î·È ÙËÓ ·ÔÙÚÔ‹ ÂÌÊ¿ÓÈÛ˘ ÎÔÏÈ΋˜ ·ÈÌfiÚÚÔÈ·˜ (11). ∞fi ÙÔ˘˜ ÂÎÏÂÎÙÈÎÔ‡˜ ·Ó·ÛÙÔÏ›˜ ÙˆÓ ˘Ô‰Ô¯¤ˆÓ ÙˆÓ ÔÈÛÙÚÔÁfiÓˆÓ ¤¯ÂÈ ‰ÔÎÈÌ·Ûı› Ë tamoxifen Ì ÂÓı·ÚÚ˘ÓÙÈο ·ÔÙÂϤÛÌ·Ù· Î·È ÙÒÚ· Â›Ó·È Û ÎÏÈÓÈ΋ ‰ÔÎÈÌ‹ Ë fulvestrant (10). ™ÙËÓ ·ÛıÂÓ‹ Ì·˜ ¯ÔÚËÁ‹ıËΠÏÂÙÚÔ˙fiÏË Ì ηϿ ·ÔÙÂϤÛÌ·Ù·. ∏ ÈÓ҉˘ ‰˘ÛÏ·Û›· ÙˆÓ ÔÛÙÒÓ (π¢√) Â›Ó·È Ë Û˘¯ÓfiÙÂÚË ÌË ÂÓ‰ÔÎÚÈÓÈ΋ ÂΉ‹ÏˆÛË ÙÔ˘ MAS (4698%) (4,5,6). ∏ Û˘Ó‹ı˘ ËÏÈΛ· ¤Ó·Ú͢ ÙˆÓ Û˘ÌÙˆÌ¿ÙˆÓ Â›Ó·È Ë ‚ÚÂÊÈ΋ ËÏÈΛ·. ∏ π¢√ Â›Ó·È Î˘Ú›ˆ˜ ÔÏ˘ÔÛÙoÙÈ΋, ·ÏÏ¿ ÛÙÔ 1/3 ÙˆÓ ·ÛıÂÓÒÓ ÂÌÊ·Ó›˙ÂÙ·È ˆ˜ ÌÔÓÔÔÛÙÔÙÈ΋ ‚Ï¿‚Ë (12). ™˘¯ÓfiÙÂÚ· ÚÔÛ‚¿ÏÏÔÓÙ·È Ù· Ì·ÎÚ¿ ÔÛÙ¿, ÔÈ Ï¢ڤ˜ Î·È Ù· ÔÛÙ¿ ÙÔ˘ ÎÚ·Ó›Ô˘. ∆Ô ÂÁÁ‡˜ ÌËÚÈ·›Ô ÚÔÛ‚¿ÏÏÂÙ·È Û¯Â‰fiÓ Û fiÏÔ˘˜ ÙÔ˘˜ ·ÛıÂÓ›˜ Ì π¢√ (fiˆ˜ ηÈ

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ÛÙËÓ ·ÛıÂÓ‹ Ì·˜) Î·È ¤¯ÂÈ ¯·Ú·ÎÙËÚÈÛÙÈ΋ ·ÎÙÈÓÔÏÔÁÈ΋ ÂÈÎfiÓ· Ô˘ ÂÚÈÁÚ¿ÊÂÙ·È Û·Ó “ÁÎÏ›ÙÛ· ÙÔ˘ ‚ÔÛÎÔ‡” (13,14). √È ‰˘ÛÏ·ÛÙÈΤ˜ ÂÚÈÔ¯¤˜ ÌÔÚ› Ó· Â›Ó·È ·Û˘Ìو̷ÙÈΤ˜ Î·È Ó· ·ÓȯÓ‡ÔÓÙ·È ÌfiÓÔ ÛÙÔÓ ·ÂÈÎÔÓÈÛÙÈÎfi ¤ÏÂÁ¯Ô ÙˆÓ ÔÛÙÒÓ ‹ Ó· Û˘Óԉ‡ÔÓÙ·È ·fi ¿ÏÁÔ˜, ÔÛÙÈΤ˜ ·Ú·ÌÔÚÊÒÛÂȘ, ÈÂÛÙÈο Ê·ÈÓfiÌÂÓ· ÎÚ·ÓÈ·ÎÒÓ ÓÂ‡ÚˆÓ (΢ڛˆ˜ ÔÙÈÎfi Î·È ·ÎÔ˘ÛÙÈÎfi) Î·È ·ıÔÏÔÁÈο ηٿÁÌ·Ù· (8). ∆Ô 85% ÙˆÓ ·ÛıÂÓÒÓ Ì MAS Î·È π¢√ ¤¯ÂÈ ˘ÔÛÙ› ÙÔ˘Ï¿¯ÈÛÙÔÓ ¤Ó· οٷÁÌ·, ÂÓÒ ÙÔ 60% ¤¯ÂÈ >2 ηٿÁÌ·Ù·, Ù· ÔÔ›· ¤¯Ô˘Ó ·ÓÙÈÌÂÙˆÈÛı› ¯ÂÈÚÔ˘ÚÁÈο (14). ∏ Û˘¯ÓfiÙËÙ· ÙˆÓ Î·Ù·ÁÌ¿ÙˆÓ ÁÂÓÈο ÌÂÈÒÓÂÙ·È ÌÂÙ¿ Ù· 10 ¯ÚfiÓÈ· ˙ˆ‹˜ (15). ∏ ‚·Ú‡ÙËÙ· ÙˆÓ ÔÛÙÈÎÒÓ ‚Ï·‚ÒÓ Î·È Ë Û˘¯ÓfiÙËÙ· ÙˆÓ Î·Ù·ÁÌ¿ÙˆÓ Û˘Û¯ÂÙ›˙ÂÙ·È Î˘Ú›ˆ˜ ÌÂ Û˘Ó˘¿Ú¯Ô˘Û· ÓÂÊÚÈ΋ ·ÒÏÂÈ· ʈÛÊfiÚÔ˘, ·ÏÏ¿ Î·È Ì ÙËÓ ‡·ÚÍË ÂÓ‰ÔÎÚÈÓÔ·ıÂÈÒÓ Ô˘ ¤¯Ô˘Ó Â›‰Ú·ÛË ÛÙÔÓ ÔÛÙÈÎfi ÌÂÙ·‚ÔÏÈÛÌfi (15). ∏ ıÂÚ·›· Ù˘ ̤ÙÚÈ·˜ ‹ ‚·ÚÈ¿˜ π¢√ Ì ‰ÈʈÛÊÔÓÈο (·ÌȉÚÔÓ¿ÙË) ¤¯ÂÈ ‰ÒÛÂÈ ÂÓı·ÚÚ˘ÓÙÈο ·ÔÙÂϤÛÌ·Ù· (16). ∏ ·ÛıÂÓ‹˜ Ì·˜ ‰ÂÓ ÂÌÊ¿ÓÈÛÂ Û˘ÌÙÒÌ·Ù· ÏfiÁˆ Ù˘ π¢√, Ë ‰È¿ÁÓˆÛË ¤ÁÈÓ Ì ÙÔÓ ·ÂÈÎÔÓÈÛÙÈÎfi ¤ÏÂÁ¯Ô ÙˆÓ ÔÛÙÒÓ Î·È ‰ÂÓ ˘‹Ú¯Â ¤Ó‰ÂÈÍË ¯ÔÚ‹ÁËÛ˘ ıÂÚ·›·˜ ÙÔ˘Ï¿¯ÈÛÙÔÓ ÚÔ˜ ÙÔ ·ÚfiÓ. √È ÌÂÏ·¯ÚˆÌ·ÙÈΤ˜ (café-au-lait) ÎËÏ›‰Â˜ ÙÔ˘ ‰¤ÚÌ·ÙÔ˜ ÛÙÔ MAS Â›Ó·È ¯·Ú·ÎÙËÚÈÛÙÈΤ˜ Î·È ÙÔ ‰È·ÊÔÚÔÔÈÔ‡Ó ·fi ÙË Ó¢ÚÈӈ̿وÛË, fiÔ˘ Î·È ÂΛ ÔÈ café-au-lait ÎËÏ›‰Â˜ Â›Ó·È Û˘ÛÙ·ÙÈÎfi ÛÙÔÈ¯Â›Ô Ù˘ ÓfiÛÔ˘. ™ÙÔ MAS ¤¯Ô˘Ó ·ÓÒÌ·ÏË ‰·ÓÙÂψً ·Ú˘Ê‹, ‰ÂÓ ÍÂÂÚÓÔ‡Ó ÔÙ¤ ÙË Ì¤ÛË ÁÚ·ÌÌ‹ Î·È ·ÎÔÏÔ˘ıÔ‡Ó ÙȘ ÁÚ·Ì̤˜ Blaschko. ™˘Ó‹ıˆ˜ ÂÌÊ·Ó›˙ÔÓÙ·È ˆ˜ ÌÂÁ¿Ï˜ ÌÂÏ·¯ÚˆÌ·ÙÈΤ˜ ÂÚÈÔ¯¤˜ ÛÙÔÓ ÎÔÚÌfi, ΢ڛˆ˜ ηٿ ÙË ‚ÚÂÊÈ΋ ËÏÈΛ·. ™ÙÔÓ ÚÒÙÔ Ì‹Ó· ÂÌÊ¿ÓÈÛ˘ ¤¯Ô˘Ó Ù¿ÛË Â¤ÎÙ·Û˘, ·ÏÏ¿ ÌÂÙ¿ ÛÙ·ıÂÚÔÔÈÔ‡ÓÙ·È. ™ÙËÓ ·ÛıÂÓ‹ Ì·˜ ˘‹Ú¯Â Ì›· ÌÂÏ·¯ÚˆÌ·ÙÈ΋ ÎËÏ›‰·, Ë ÔÔ›· ‰ÂÓ Â›¯Â Ù· ¯·Ú·ÎÙËÚÈÛÙÈο ÙÔ˘ MAS. ∏ ˘ÂÚ¤ÎÎÚÈÛË ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ (∞√) ÂÌÊ·Ó›˙ÂÙ·È ÂÚ›Ô˘ ÛÙÔ 21% ÙˆÓ ·ÛıÂÓÒÓ Ì MAS (4,5,6) Î·È Ë Î‡ÚÈ· ÎÏÈÓÈ΋ ÂΉ‹ÏˆÛË Â›Ó·È Ô Ù·¯‡˜ Ú˘ıÌfi˜ ۈ̷ÙÈ΋˜ ·Ó¿Ù˘Í˘. ∂ӉȷʤÚÔÓ ·ÚÔ˘ÛÈ¿˙ÂÈ Ë Â›‰Ú·ÛË Ù˘ Û˘Ó‡·Ú͢ ˘ÂÚ¤ÎÎÚÈÛ˘ ∞√ Î·È ¶¶∏ ÛÙË ÛˆÌ·ÙÈ΋ ·‡ÍËÛË Û ·ÛıÂÓ›˜ Ì MAS. ∆Ô ÙÂÏÈÎfi ‡„Ô˜ ÛÙËÓ ÂÚ›ÙˆÛË ·˘Ù‹ Â›Ó·È Û˘Ó‹ıˆ˜ Ê˘ÛÈÔÏÔÁÈÎfi, ÏfiÁˆ Ù˘ ˘ÂÚÔ¯‹˜ Ù˘ ‰Ú¿Û˘ Ù˘ ∞√ ¤Ó·ÓÙÈ Ù˘ ¤ÎıÂÛ˘ ÛÙ· ÔÈÛÙÚÔÁfiÓ· (17). ∂Âȉ‹ Ë ÎÏÈÓÈ΋ ÂÌÊ¿ÓÈÛË Ù˘ ˘ÂÚ¤ÎÎÚÈÛ˘ ∞√ ÌÔÚ› Ó· Â›Ó·È ‹È·, fiÏÔÈ ÔÈ ·ÛıÂÓ›˜ Ì MAS Ú¤ÂÈ Ó· ÂϤÁ¯ÔÓÙ·È ÂÚÈÔ‰Èο Ì ̤ÙÚËÛË IGF-1 ÛÙÔÓ ÔÚfi Î·È Èı·ÓÒ˜ Ì OGTT. ™ÙËÓ ·ÛıÂÓ‹ Ì·˜, Ô ¤ÏÂÁ¯Ô˜ ÁÈ· ˘ÂÚ¤ÎÎÚÈÛË ·˘ÍËÙÈ΋˜ ÔÚÌfiÓ˘ Ì OGTT Î·È Ì¤ÙÚËÛË IGF-1 ÛÙÔÓ ÔÚfi, ÛÙ· ·Ú¯Èο ÛÙ¿‰È· Î·È ÌÂÙ·ÁÂÓ¤ÛÙÂÚ·, ‹Ù·Ó ¿ÓÙÔÙ ·ÚÓËÙÈÎfi˜.

∏ ÂÌÊ¿ÓÈÛË ¿ÏÏˆÓ ÂÓ‰ÔÎÚÈÓÔ·ıÂÈÒÓ, fiˆ˜ ÙÔ˘ ˘ÂÚı˘ÚÂÔÂȉÈÛÌÔ‡ Î·È ÙÔ˘ Û˘Ó‰ÚfiÌÔ˘ Cushing, ÛÙ· Ï·›ÛÈ· ÙÔ˘ MAS, Â›Ó·È Û¿ÓÈ· (4,5,6), ÂÓÒ ÛÙËÓ ·ÛıÂÓ‹˜ Ì·˜ Ô ·ÓÙ›ÛÙÔȯԘ ¤ÏÂÁ¯Ô˜ ‹Ù·Ó ·ÚÓËÙÈÎfi˜. √È ÂΉËÏÒÛÂȘ ·fi ÙËÓ Î·Ú‰È¿ Û ·ÛıÂÓ›˜ Ì MAS Â›Ó·È Î·Ú‰ÈÔÌÂÁ·Ï›·, Â›ÌÔÓË Ù·¯˘Î·Ú‰›·, ˘¤ÚÙ·ÛË Î·È ·ÈÊÓ›‰ÈÔ˜ ı¿Ó·ÙÔ˜ (8). ™Â ηډȷÎfi ÈÛÙfi ·ÛıÂÓÔ‡˜ Ì MAS Ô˘ ·‚›ˆÛ ·ÈÊÓ›‰È· ‚Ú¤ıËÎ·Ó ÌÂÙ·ÏÏ¿ÍÂȘ ÛÙË Gsa ˘ÔÔÌ¿‰·. H ·ÚÚ˘ıÌÈÔÁfiÓÔ˜ Î·È Î·Ú‰ÈÔÙÔÍÈ΋ ‰Ú¿ÛË ÙÔ˘ cAMP Â›Ó·È ÁÓˆÛÙ‹ Î·È ÌÔÚ› Ó· ÂÌϤÎÂÙ·È ÛÙËÓ ·ıÔÁ¤ÓÂÈ· ·ÈÊÓ›‰ÈˆÓ Î·È ÚfiˆÚˆÓ ı·Ó¿ÙˆÓ (8,12). ∏ ̤ÛË Û˘¯ÓfiÙËÙ· Ù·˘ÙÔÔ›ËÛ˘ ÌÂÙ·ÏÏ¿ÍÂˆÓ Ù˘ Gsa Û ÚÔۂ‚ÏË̤ÓÔ˘˜ ÈÛÙÔ‡˜ Û ÙÚÂȘ ÚfiÛÊ·Ù˜ ÌÂϤÙ˜ ÂÁÁ›˙ÂÈ ÙÔ 45%. ∂ȉÈο Ë Û˘¯ÓfiÙËÙ· ·Ó›¯Ó¢Û˘ ÌÂÙ·ÏÏ¿ÍÂˆÓ Â›Ó·È ¯·ÌËÏ‹ ÛÙÔ ‰¤ÚÌ· Î·È ÙÔ ÂÚÈÊÂÚÈÎfi ·›Ì·, ÂÓÒ ·Ú·Ì¤ÓÂÈ ˘„ËÏ‹ Û ¿ÏÏÔ˘˜ ÈÛÙÔ‡˜, fiˆ˜ ÙȘ ˆÔı‹Î˜ Î·È Ù· ÔÛÙ¿ (3,4,18). ™ÙËÓ ·ÛıÂÓ‹ Ì·˜, Ô ¤ÏÂÁ¯Ô˜ ÂÚÈÊÂÚÈÎÔ‡ ·›Ì·ÙÔ˜ ÁÈ· ·Ó›¯Ó¢ÛË Gsa ÌÂÙ·ÏÏ¿ÍÂˆÓ ·¤‚Ë ·ÚÓËÙÈÎfi˜. ™˘ÌÂÚ·ÛÌ·ÙÈο, ÙÔ ª∞S Â›Ó·È Ì›· Û¿ÓÈ·, ÂÍÂÏÈÛÛfiÌÂÓË ÓfiÛÔ˜, Ì ÔÈÎÈÏ›· ÂΉËÏÒÛÂˆÓ ·fi ÔÏÏ¿ Û˘ÛÙ‹Ì·Ù·. √ ÎÏÈÓÈÎfi˜ ÁÈ·ÙÚfi˜ ı· Ú¤ÂÈ Ó· ˘Ô„È¿˙ÂÙ·È ÙË ÓfiÛÔ ·ÎfiÌ· Î·È Û ‡·ÚÍË ÌÂÌÔÓˆÌ¤ÓˆÓ ÎÏÈÓÈÎÒÓ Â˘ÚËÌ¿ÙˆÓ Ô˘ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ÛÙËÓ ÎÏ·ÛÈ΋ ÙÚÈ¿‰· ÙÔ˘ MAS. ∏ Ù·ÎÙÈ΋ ·Ú·ÎÔÏÔ‡ıËÛË Î·È Ë ¤ÁηÈÚË ·ÓÙÈÌÂÙÒÈÛË Ù˘ ˘ÂÚ¤ÎÎÚÈÛ˘ ÔÚÌÔÓÒÓ Î·È Ù˘ ÛÔ‚·Ú‹˜ π¢√ Â›Ó·È ·Ó·Áη›·. °ÂÓÈο, Ë ÚfiÁÓˆÛË Â›Ó·È Î·Ï‹ ÛÙȘ ‹Ș ÌÔÚʤ˜ Ù˘ ÓfiÛÔ˘, fï˜ ˘¿Ú¯Ô˘Ó ˘ÔÔÌ¿‰Â˜ ·ÛıÂÓÒÓ Ì ‚·Ú‡Ù·Ù˜ ÂΉËÏÒÛÂȘ ·fi Ù· ÔÛÙ¿ Î·È ÔÏÏ·Ϥ˜ ÂÓ‰ÔÎÚÈÓÔ¿ıÂȘ. ∏ ÚÔÛ‚ÔÏ‹ ÙÔ˘ ηډȷÎÔ‡ ÈÛÙÔ‡ ·˘Í¿ÓÂÈ ÙÔÓ Î›Ó‰˘ÓÔ ÁÈ· ÚfiˆÚÔ Ë ·ÈÊÓ›‰ÈÔ ı¿Ó·ÙÔ.

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16. Lala R, Matarazzo P, Andreo M, Marzari D, Bellone J, Corrias A, et al. Bisphosphonate treatment of bone fibrous dysplasia in McCune-Albright syndrome. J Pediatr Endocrinol Metab 2006;19:583-593.

17. Akintoye SO, Chebli C, Booher S, Feuillan P, Kushner H, Leroith D, et al. Characterization of gsp-mediated growth hormone excess in the context of McCune-Albright syndrome. J Clin Endocrinol Metab 2002;87:5104-5112.

18. De Sanctis L, Romagnolo D, Greggio N, Genitori L, Lala R, de Sanctis C. Searching for Arg201 mutations in the GNAS1 gene in Italian patients with McCune-Albright syndrome. J Pediatr Endocrinol Metab 2002;15:883-889.

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323

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∂ÈÎfiÓ· 1. ™ÙË ÊˆÙÔÁÚ·Ê›· ‰È·ÎÚ›ÓÂÙ·È Ë Ú·È‚fiÙËÙ· Ù˘ ·ÚÈÛÙÂÚ‹˜ ÎÓ‹Ì˘ Î·È ÙÔ Â˘ı‡ÁÚ·ÌÌÔ Ù˘ ‰ÂÍÈ¿˜ ÎÓ‹Ì˘.

∂ÈÎfiÓ· 2. ∞ÎÙÈÓÔÁÚ·Ê›· ‰ÂÍÈ¿˜ ÎÓ‹Ì˘.

∂ÈÎfiÓ· 3. ™ÈÓıËÚÔÁÚ¿ÊËÌ· ÔÛÙÒÓ Ì Tc99.

µ’ √ÚıÔ·È‰ÈÎfi ∆Ì‹Ì·, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ ∞ıËÓÒÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”

ÕÚÚÂÓ ‚Ú¤ÊÔ˜ 16 ÌËÓÒÓ ÚÔÛÎÔÌ›ÛÙËΠÛÙËÓ ÎÏÈÓÈ΋ Ì·˜ ÁÈ· ‰È·Ù·Ú·¯‹ ÙÔ˘ ¿ÍÔÓ· ÙˆÓ Î¿Ùˆ ¿ÎÚˆÓ Î·È ÂÏ·ÊÚ¿ ¯ˆÏfiÙËÙ·. ◊Ù·Ó ÙÔ ÚÒÙÔ ·È‰› Ê·ÈÓÔÙ˘Èο ˘ÁÈÒÓ ÁÔÓ¤ˆÓ Ì ÂÚÈÁÂÓÓËÙÈÎfi ÈÛÙÔÚÈÎfi ÂχıÂÚÔ. ∆Ô ÔÈÎÔÁÂÓÂÈ·Îfi ·Ó·ÌÓËÛÙÈÎfi ÁÈ· Û˘ÁÁÂÓ›˜ ·Ú·ÌÔÚÊÒÛÂȘ ‹Ù·Ó Â›Û˘ ·ÚÓËÙÈÎfi. ™ÙËÓ ·ÓÙÈÎÂÈÌÂÓÈ΋ ÂͤٷÛË, ÙÔ ‚Ú¤ÊÔ˜ ·ÚÔ˘Û›·˙ ڷȂfiÙËÙ· Ù˘ ·ÚÈÛÙÂÚ‹˜ ÎÓ‹Ì˘, ÂÓÒ Ë ‰ÂÍÈ¿ ÎÓ‹ÌË ÂÌÊ·ÓÈ˙fiÙ·Ó Â˘ı‡ÁÚ·ÌÌË (∂ÈÎfiÓ· 1) Ì ¢·ÈÛıËÛ›· ÛÙËÓ „ËÏ¿ÊËÛ‹ Ù˘. ∏ ÎÈÓËÙÈÎfiÙËÙ· ÙÔ˘ ÁfiÓ·ÙÔ˜ Î·È Ù˘ Ô‰ÔÎÓËÌÈ΋˜ ¿ÚıÚˆÛ˘ ÂϤÁ¯ıËΠÏ‹Ú˘ Î·È ·ÓÒ‰˘ÓË. √È ·ÎÙÈÓÔÁڷʛ˜ ¤‰ÂÈÍ·Ó ÛÎÏ‹Ú˘ÓÛË ÙÔ˘ ÊÏÔÈÔ‡ Ù˘ ‰ÂÍÈ¿˜ ÎÓ‹Ì˘ Î·È Â˘ı˘ÁÚ¿ÌÌÈÛË ÙÔ˘ ¿ÍÔÓ· ·˘Ù‹˜, ¯ˆÚ›˜ Û·Ê‹ Ï˘ÙÈ΋ ‚Ï¿‚Ë (∂ÈÎfiÓ· 2). ∆Ô ÛÈÓıËÚÔÁÚ¿ÊËÌ· ÔÛÙÒÓ Ì ڷ‰ÈÂÓÂÚÁfi Ù¯ӋÙÈÔ (Tc99) ·ÔÎ¿Ï˘„ ·˘ÍË̤ÓÔ ÌÂÙ·‚ÔÏÈÛÌfi ÛÙËÓ ›‰È· ÂÚÈÔ¯‹ Î·È ÛÙȘ ÙÚÂȘ Ê¿ÛÂȘ (∂ÈÎfiÓ· 3). ∏ Ì·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· ¤‰ÂÈÍÂ, ÂÎÙfi˜ ·fi ÛÎÏ‹Ú˘ÓÛË ÙÔ˘ ÊÏÔÈÔ‡, ·ÏÏÔÈÒÛÂȘ ÛÙÔÓ ÔÛÙÈÎfi Ì˘ÂÏfi (∂ÈÎfiÓ· 4). Àfi ÁÂÓÈ΋ ·Ó·ÈÛıËÛ›· Î·È Ì ·ÔÛÙÂÈڈ̤ÓË ›Û¯·ÈÌË ÂÚ›‰ÂÛË, ¤ÁÈÓ ÚÔÛ¤ÁÁÈÛË Ù˘ ÌÂÛfiÙËÙ·˜ Ù˘ ‰ÂÍÈ¿˜ ÎÓ‹Ì˘ Î·È ·Ó‡ÚÂÛË ÙÔ˘ ÛÎÏËÚ˘ÓÙÈÎÔ‡ ÊÏÔÈÔ‡. ¢È¿ ̤ÛÔ˘ ÌÈÎÚÔ‡ ·Ú·ı‡ÚÔ˘, ÚÔÛÂÏ¿ÛÙËÎÂ Ô ÔÛÙÈÎfi˜ Ì˘ÂÏfi˜ Î·È ·ÎÔÏÔ‡ıËÛ ÂÈÌÂÏ‹˜ ηı·ÚÈÛÌfi˜ ·fi Ù· ÊÏÂÁÌÔÓÒ‰Ë ÛÙÔȯ›· Î·È ·fiÍÂÛË Ù˘ ‰ËÌÈÔ˘ÚÁËı›۷˜ ÎÔÈÏfiÙËÙ·˜. ∏ ÈÛÙÔÏÔÁÈ΋ ÂͤٷÛË ÙˆÓ ·Ê·ÈÚÂı¤ÓÙˆÓ ÈÛÙÒÓ ·Ó¤‰ÂÈÍ “ÙÌ‹Ì·Ù· ˆÚ›ÌÔ˘ ÂÙ·ÏÈÒ‰Ô˘˜ ÔÛÙÔ‡ ·fi ÙÔ ÊÏÔÈfi ÙÔ˘ ÔÛÙÔ‡ ˆ˜ Î·È ÙÌ‹Ì·Ù· ÂÚÈÔÛÙ¤Ô˘, Ì ÂÎÙÂٷ̤ÓË Ó¤ÎÚˆÛË ÔÛÙÂÔ‰ÔΛ‰ˆÓ Î·È ›ÓˆÛË ÙˆÓ Ì˘ÂÏÔ¯ÒÚˆÓ, Ï‹ÚÂȘ ÊÏÂÁÌÔÓˆ‰ÒÓ Î˘ÙÙ¿ÚˆÓ”. ∆· ÎÏÈÓÈο ÛËÌ›· Î·È Ù· Û˘ÌÙÒÌ·Ù· ˘Ô¯ÒÚËÛ·Ó ÛÙËÓ ÚÒÙË ÌÂÙÂÁ¯ÂÈÚËÙÈ΋ ÂÚ›Ô‰Ô, ÂÓÒ ÙÔ ÔÛÙÔ‡Ó ¤‰ÂÈÍ ÚÔԉ¢ÙÈ΋ ·Ó·Î·Ù·Û΢‹ Î·È ÛÙ·‰È·Î‹ ‰ÈfiÚıˆÛË Ù˘ ·Ú·ÌfiÚʈÛ˘ ÙÔ˘˜ ÂfiÌÂÓÔ˘˜ Ì‹Ó˜.

AÏÏËÏÔÁÚ·Ê›·: ¡ÈÎfiÏ·Ô˜ ª·ÚΤ·˜ markeasn@otenet.gr µ’ √ÚıÔ·È‰ÈÎfi ∆Ì‹Ì·, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ ∞ıËÓÒÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”

¶Èı·Ó¤˜ ‰È·ÁÓÒÛÂȘ: 1. √ÛÙÂÔÂȉ¤˜ ÔÛÙ¤ˆÌ· 2. ∫·ÏfiËı˜ ÔÛÙÂÔ‚Ï¿Ûو̷ 3. ÃÚfiÓÈ· ÛÎÏËÚ˘ÓÙÈ΋ ÔÛÙÂÔÌ˘ÂÏ›Ùȉ· Ù‡Ô˘ Garré 4. ™¿ÚΈ̷ Ewing

∏ ·¿ÓÙËÛË ÛÙË ÛÂÏ›‰· 330 ∂ÈÎfiÓ· 4. ª·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· ÎÓËÌÒÓ. ¶·È‰È·ÙÚÈ΋ 2008;71:323,330

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¡¤· ÁÈ· Ù· ÂÌ‚fiÏÈ· 2008 ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, ¶·ÓÂÈÛÙ‹ÌÈÔ ∫Ú‹Ù˘

∂. °·Ï·Ó¿Î˘

∞ÏÏËÏÔÁÚ·Ê›·: ∂ÌÌ·ÓÔ˘‹Ï °·Ï·Ó¿Î˘ egalanak@med.uoc.gr ¶·È‰È·ÙÚÈ΋ ∫ÏÈÓÈ΋, ¶·ÓÂÈÛÙ‹ÌÈÔ ∫Ú‹Ù˘

Update on vaccination 2008

Department of Paediatrics, University of Crete

¶ÚÔÁÚ¿ÌÌ·Ù· ÂÌ‚ÔÏÈ·ÛÌÒÓ. ™Â ÚÔËÁÔ‡ÌÂÓÔ Ù‡¯Ô˜ Ù˘ ¶·È‰È·ÙÚÈ΋˜ (2008;71:16670) ·ÚÔ˘ÛÈ¿ÛıËΠÙÔ ∂ıÓÈÎfi ¶ÚfiÁÚ·ÌÌ· ∂Ì‚ÔÏÈ·ÛÌÒÓ 2008 ÁÈ· ÙËÓ ∂ÏÏ¿‰·, Ì ÛËÌ·ÓÙÈΤ˜ ·ÏÏ·Á¤˜: ÂÈÛ·ÁˆÁ‹ ÂÌ‚ÔÏ›ˆÓ ÈÔ‡ ÙˆÓ ·ÓıÚˆ›ÓˆÓ ıËÏˆÌ¿ÙˆÓ Î·È Ë·Ù›Ùȉ·˜ ∞, Â¤ÎÙ·ÛË TdaP ÛÙËÓ ÂÊ˂›·, ÚÔÛı‹ÎË ‰Â‡ÙÂÚ˘ ‰fiÛ˘ ÂÌ‚ÔÏ›Ô˘ ·ÓÂÌ¢ÏÔÁÈ¿˜ Î·È Ô‰ËÁ›Â˜ ÂÌ‚ÔÏÈ·ÛÌÔ‡ ‚ÚÂÊÒÓ ÁÈ· Ë·Ù›Ùȉ· µ, ·Ó¿ÏÔÁ· Ì ÙË ÊÔÚ›· HBsAg Ù˘ ÌËÙ¤Ú·˜. ™ÙÔ Pediatrics π·ÓÔ˘·Ú›Ô˘ 2008 (2008;121: 219-20) ·ÚÔ˘ÛÈ¿ÛıËÎÂ Ë ·Ó·Óˆ̤ÓË ¤Î‰ÔÛË ÙÔ˘ ¶ÚÔÁÚ¿ÌÌ·ÙÔ˜ ∂Ì‚ÔÏÈ·ÛÌÒÓ ÁÈ· ÙȘ ∏¶∞. ∞fi ÙȘ ·ÏÏ·Á¤˜ ÛËÌÂÈÒÓÔÓÙ·È ÔÈ Û˘ÛÙ¿ÛÂȘ ÁÈ· 1 ‰fiÛË Û˘˙¢Á̤ÓÔ˘ Ó¢ÌÔÓÈÔÎÔÎÎÈÎÔ‡ Û ·ÓÂÌ‚ÔÏ›·ÛÙ· Ó‹È· 24-59 ÌËÓÒÓ, ÁÈ· 1 ‰fiÛË ÙÂÙÚ·‰‡Ó·ÌÔ˘ Û˘˙¢Á̤ÓÔ˘ ÌËÓÈÁÁÈÙȉÔÎÔÎÎÈÎÔ‡ ÁÈ· fiÏ· Ù· ·È‰È¿ 11-18 ÂÙÒÓ Î·È ÁÈ· Ù· ˘„ËÏÔ‡ ÎÈÓ‰‡ÓÔ˘ ÛÙ· 2-10 ¤ÙË, ηıÒ˜ Î·È ÁÈ· ÙË ¯ÔÚ‹ÁËÛË ÂÌ‚ÔÏ›Ô˘ ÁÚ›˘ ÛÙ· ˘ÁÈ‹ ‚Ú¤ÊË Î·È Ó‹È·.

∂Ì‚fiÏÈÔ ÁÈ· ÙÔÓ Èfi ÙˆÓ ·ÓıÚˆ›ÓˆÓ ıËψ̿وÓ. ™‡Ìʈӷ Ì ·Ó·ÎÔ›ÓˆÛË Ù˘ ÂÙ·ÈÚ›·˜ GlaxoSmithKline (Reuters Health, 10 ª·ÚÙ›Ô˘ 2008), ÂÍÔ˘‰ÂÙÂÚˆÙÈο ·ÓÙÈÛÒÌ·Ù· ·fi ÙÔ ÂÌ‚fiÏÈÔ Cervarix ‰È·ÙËÚÔ‡ÓÙ·È ÁÈ· ÂÚÈÛÛfiÙÂÚÔ ·fi 6 ¤ÙË, ÙÔ ÌÂÁ·Ï‡ÙÂÚÔ ÂȂ‚·ÈˆÌ¤ÓÔ ‰È¿ÛÙËÌ· ¤ˆ˜ ÙÒÚ·. ∏ ÚÔÛÙ·Û›·, fiˆ˜ Î·È ÂΛÓË ÙÔ˘ Gardasil/Merck, ·Ó·Ì¤ÓÂÙ·È Ì·ÎÚÔ¯ÚfiÓÈ·, ˆÛÙfiÛÔ ÌfiÓÔ Ô ¯ÚfiÓÔ˜ ı· ‰Â›ÍÂÈ ·Ó Î·È fiÙ ¯ÚÂÈ¿˙ÂÙ·È ·Ó·ÌÓËÛÙÈ΋ ‰fiÛË.

∂Ì‚fiÏÈÔ ÈÔ‡ ÚfiÙ·. ∞fi ÙÔ 2006 Ô˘ ÂÁÎÚ›ıËΠÛÙȘ ∏¶∞ ÙÔ RotaTeq®/Merck (Û¯‹Ì· 3 ‰fiÛˆÓ: 2, 4 Î·È 6 Ì‹Ó˜) Î·È ¤ˆ˜ ÙÔ ª¿ÈÔ ÙÔ˘ 2007, ۯ‰fiÓ Ù· ÌÈÛ¿ ‚Ú¤ÊË 3 ÌËÓÒÓ ‹Ú·Ó ÙËÓ ·Ú¯È΋ ‰fiÛË ÂÌ‚ÔÏ›Ô˘ (MMWR 2008;57:398-400). ¶ÚfiÛÊ·ÙË ·Ó·ÎÔ›ÓˆÛË ÙÔ˘ CDC (Reuters Health, 15 πÔ˘Ó›Ô˘ 2008) ˘Ô‰ÂÈÎÓ‡ÂÈ fiÙÈ Ë ÂÊ·ÚÌÔÁ‹ ÙÔ˘ ÂÌ‚ÔÏ›Ô˘ ÛÙȘ ∏¶∞ ·Ó¤ÛÙÂÈÏ Â› ÙÚ›ÌËÓÔ (·fi ÙÔ ¡Ô¤Ì‚ÚÈÔ ÛÙÔ ºÂ‚ÚÔ˘¿ÚÈÔ) ÙËÓ ¤Ó·ÚÍË ÙÔ˘ ÂÙ‹ÛÈÔ˘ ·̷ÙÔ˜ Ù˘ ÓÔÛËÚfiÙËÙ·˜.

∂Ì‚fiÏÈÔ ÁÈ· ÙÔ ÌËÓÈÁÁÈÙȉfiÎÔÎÎÔ C. ∞Ó·ÌÓËÛÙÈ΋ ‰fiÛË Û˘˙¢Á̤ÓÔ˘ ÂÌ‚ÔÏ›Ô˘ ÁÈ· ÙÔ ÌËÓÈÁÁÈÙȉfiÎÔÎÔÎÎÔ ÔÚÔÔÌ¿‰·˜ C Â›Ó·È ÂӉ¯Ô̤ӈ˜ ··Ú·›ÙËÙË ÓˆÚ›˜ ÛÙËÓ ÂÊ˂›· (BMJ 2008;336:1487-91). ∏ ÌÂϤÙË ·fi ÙËÓ √ÍÊfiÚ‰Ë ÛÙËÚ›¯ıËΠ۠‰Â‰Ô̤ӷ ·fi ÙËÓ ÂÈÙ˘¯Ë̤ÓË ÂÎÛÙÚ·Ù›· ÂÌ‚ÔÏÈ·ÛÌÔ‡ ÙÔ˘ 1999-2000. ¢ÂÓ ‚Ú¤ıËÎ·Ó ÛËÌ·ÓÙÈΤ˜ ‰È·ÊÔÚ¤˜ ÛÙË Ì·ÎÚÔ¯ÚfiÓÈ· ·Ú·ÌÔÓ‹ ·ÓÙÈÛˆÌ¿ÙˆÓ ·Ó¿ÌÂÛ· ÛÙ· 3 ÂÌ‚fiÏÈ· Ô˘ ›¯·Ó ¯ÚËÛÈÌÔÔÈËı› (Menjugate/Novartis, Meningitec/Wyeth, NeisVac-C/Baxter).

Correspondence: Emmanouil Galanakis egalanak@med.uoc.gr Department of Paediatrics, University of Crete

Paediatriki 2008;71:324-326

∂. Galanakis

⁄ÛÙÂÚ· ·fi ·Ó·ÛÎfiËÛË ÌÂÏÂÙÒÓ ·ÛÊ·Ï›·˜, ÛÙȘ 3 ∞ÚÈÏ›Ô˘ 2008 ÙÔ FDA ÂÓ¤ÎÚÈÓÂ Î·È ÙÔ Rotarix®/GlaxoSmithKline (Û¯‹Ì· 2 ‰fiÛˆÓ, Ë ÚÒÙË ÛÙȘ 6 ‚‰ÔÌ¿‰Â˜, Ë ‰Â‡ÙÂÚË ÚÈÓ ·fi ÙȘ 24 ‚‰ÔÌ¿‰Â˜ ˙ˆ‹˜ Î·È Ì ÂÏ¿¯ÈÛÙÔ ÌÂÛԉȿÛÙËÌ· 4 ‚‰ÔÌ¿‰ˆÓ). ∆Ô ÂÌ‚fiÏÈÔ Â›¯Â ‹‰Ë ÂÁÎÚÈı› Û 99 ÙÔ˘Ï¿¯ÈÛÙÔÓ ¯ÒÚ˜, Û˘ÌÂÚÈÏ·Ì‚·ÓÔÌ¤ÓˆÓ ÂÎÂ›ÓˆÓ Ù˘ ∂˘Úˆ·˚΋˜ ŒÓˆÛ˘, Î·È ¤¯Ô˘Ó ¯ÔÚËÁËı› ÂÚ› ÙȘ 12.000.000 ‰fiÛÂȘ (Pediatr Inf Dis J, Newsletter June 2008).

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PAEDIATRIC NEWS IN BRIEF ∂Ì‚fiÏÈÔ ÁÈ· ÙÔÓ Ó¢ÌÔÓÈfiÎÔÎÎÔ. ∏ ÂÈÛ·ÁˆÁ‹ ÙÔ˘ Û˘˙¢Á̤ÓÔ˘ ÂÌ‚ÔÏ›Ô˘ ¿ÏÏ·Í ÙËÓ ÂȉËÌÈÔÏÔÁ›· Ù˘ ÌËÓÈÁÁ›Ùȉ·˜ ·fi Ó¢ÌÔÓÈfiÎÔÎÎÔ ÛÙȘ ∏¶∞, Ì ٷ ÂÚÈÛÛfiÙÂÚ· ÎÚÔ‡ÛÌ·Ù· Ó· ÂÌÊ·Ó›˙ÔÓÙ·È ÙÒÚ· Û ÂÓ‹ÏÈΘ. ∏ ÁÂÓÈ΋ Ì›ˆÛË Ù˘ Â›ÙˆÛ˘ ‹Ù·Ó 33%, ˆÛÙfiÛÔ ÛÙ· ·È‰È¿ οو ÙˆÓ 2 ÂÙÒÓ ¤ÊÙ·Û ÛÙÔ 66% Î·È ÛÙ· 2-4 ÂÙÒÓ ÛÙÔ 52% (Clin Infect Dis 2008;46:1664-76). °È· ÙËÓ ∂ÏÏ¿‰·, Û ÌÂϤÙË ·fi ÙË §¿ÚÈÛ· (Pediatr Infect Dis J 2008;27:519-25) ÙÔ Û˘˙¢Á̤ÓÔ ÂÌ‚fiÏÈÔ ·ÎÔÏÔ˘ı‹ıËΠ·fi Ì›ˆÛË Ù˘ ÚÈÓÔÊ·Ú˘ÁÁÈ΋˜ ÊÔÚ›·˜ Ó¢ÌÔÓÈÔÎfiÎÎˆÓ ˘„ËÏ‹˜ ·ÓÙÔ¯‹˜ ÛÙËÓ ÂÓÈÎÈÏ›ÓË, ¯ˆÚ›˜ Ó· ·Ú·ÙËÚËı› ·‡ÍËÛË ÙÔ˘ ÔÚÔÙ‡Ô˘ 19∞. ∂Ì‚fiÏÈÔ ÁÈ· ÙËÓ Ë·Ù›Ùȉ· ∞. ªÂÙ¿ ÙËÓ ÂÊ·ÚÌÔÁ‹ ÙÔ˘ ÂÌ‚ÔÏ›Ô˘ ÛÙȘ ∏¶∞ ·fi Ù· ̤۷ Ù˘ ‰ÂηÂÙ›·˜ 1990, ÔÈ ı¿Ó·ÙÔÈ ·fi Ë·Ù›Ùȉ· ∞ ÌÂÈÒıËÎ·Ó Î·Ù¿ 32% (J Infect Dis 2008;197:1282-8). ™ÙȘ ¶ÔÏÈÙ›˜ Ì Â›ÛËÌË Û‡ÛÙ·ÛË ÂÌ‚ÔÏÈ·ÛÌÔ‡ Ë Ì›ˆÛË ‹Ù·Ó 45% Î·È ÛÙȘ ¶ÔÏÈÙ›˜ ¯ˆÚ›˜ Â›ÛËÌË Û‡ÛÙ·ÛË ‹Ù·Ó ÌfiÓÔ 23%. ∂Ì‚fiÏÈÔ MMRV (ÈÏ·Ú¿-·ÚˆÙ›Ùȉ·-ÂÚ˘ıÚ¿-·ÓÂÌ¢ÏÔÁÈ¿). ¢Â‰Ô̤ӷ Ô˘ ·ÚÔ˘ÛÈ¿ÛıËÎ·Ó ÛÙËÓ 26Ë ÂÙ‹ÛÈ· Û˘Ó¿ÓÙËÛË Ù˘ European Society for Paediatric Infectious Diseases (°ÎÚ·Ù˙, 13-17 ª·˝Ô˘ 2008) Û˘ÓËÁÔÚÔ‡Ó ÁÈ· ÙËÓ ·ÛÊ¿ÏÂÈ· Î·È ÙËÓ ·ÔÙÂÏÂÛÌ·ÙÈÎfiÙËÙ· ÙÔ˘ MMRV Ù˘ GlaxoSmithKline (Priorix-TetraTM, 2 ‰fiÛÂȘ), ÙfiÛÔ ÌfiÓÔ˘ ÙÔ˘, fiÛÔ Î·È Ì·˙› Ì ¿ÏÏ·. ∂Ì‚fiÏÈÔ ‰ÈÊıÂÚ›Ùȉ·˜-ÎÔηÙË-٤ٷÓÔ˘ Û ¤ÁÎ˘Â˜ Î·È ÓÂÔÁÓ¿. ™ÙȘ ∏¶∞, ÂÁÎÚ›ıËÎ·Ó ÙÔ 2005 ‰‡Ô ÂÌ‚fiÏÈ· Ù‡Ô˘ TdaP (Adacel/ Sanofi Pasteur ÁÈ· ËÏÈ˘ 11-64 ÂÙÒÓ Î·È Boostrix/GlaxoSmithKline ÁÈ· ËÏÈ˘ 10-18 ÂÙÒÓ), ˆ˜ 1 ‰fiÛË ÛÙË ı¤ÛË Ù˘ ·Ó·ÌÓËÛÙÈ΋˜ dT. ¶ÚfiÛÊ·Ù˜ Ô‰ËÁ›Â˜ Ù˘ ∞CIP (MMWR 2008;57:1-47) ˘ÂÓı˘Ì›˙Ô˘Ó fiÙÈ Ù· ˘¿Ú¯ÔÓÙ· ‰Â‰Ô̤ӷ ‰ÂÓ ÙÂÎÌËÚÈÒÓÔ˘Ó ÙËÓ ·ÛÊ¿ÏÂÈ· ÙÔ˘ ÂÌ‚ÔÏÈ·ÛÌÔ‡ ÁÈ· ÙËÓ ¤ÁÎ˘Ô Î·È ÙÔ Î‡ËÌ· Ô‡Ù ·Ó Ë ‰È·Ï·ÎÔ˘ÓÙȷ΋ ÌÂÙ·‚›‚·ÛË ·ÓÙÈÛˆÌ¿ÙˆÓ ·Ú¤¯ÂÈ ÚÒÈÌË ÚÔÛÙ·Û›· ηٿ ÙÔ˘ ÎÔηÙË ‹ ·ÏÏËÏÂȉڿ Ì ÙÔ Û¯‹Ì· ÂÌ‚ÔÏÈ·ÛÌÒÓ ÙÔ˘ ‚Ú¤ÊÔ˘˜. √È ·ÓÂÌ‚ÔÏ›·ÛÙ˜ ¤ÁÎ˘Â˜ ÌÔÚÔ‡Ó Ó· ÂÌ‚ÔÏÈ¿˙ÔÓÙ·È Ì ∆daP ¢ı‡˜ ÌÂÙ¿ ÙÔÓ ÙÔÎÂÙfi, ·ÏÏ¿ ·Ó ˘¿Ú¯ÂÈ ¤Ó‰ÂÈÍË, Î·È Ì Td ηٿ ÙË ‰È¿ÚÎÂÈ· Ù˘ ·ËÛ˘. ∆Ô TdaP ‰ÂÓ ·ÓÙÂӉ›ÎÓ˘Ù·È Î·Ù¿ ÙËÓ Î‡ËÛË,

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ˆÛÙfiÛÔ Ú¤ÂÈ Ó· ˙˘Á›˙ÔÓÙ·È Ì ÚÔÛÔ¯‹ ÔʤÏË Î·È ÂӉ¯fiÌÂÓÔÈ Î›Ó‰˘ÓÔÈ. ∂Ì‚fiÏÈÔ ÁÈ· ÙËÓ ÂÔ¯È΋ ÁÚ›Ë. ∏ ÂÈÙ˘¯›· ÙÔ˘ ÂÌ‚ÔÏ›Ô˘ Ù˘ ÁÚ›˘ ÂÍ·ÚÙ¿Ù·È ·fi ÙËÓ ·ÓÙÈÛÙÔȯ›· ÙÔ˘ Ì ÙÔÓ ˘‡ı˘ÓÔ Èfi οı ¤ÙÔ˘˜. ∏ ÂÚ›Ô‰Ô˜ 2007-2008 ‰ÂÓ ‹Ù·Ó ηϋ, ηıÒ˜ Ë Î¿Ï˘„Ë ‰È·Î˘Ì¿ÓıËΠοو ·fi ÙÔ 50% ·ÓÙ› ÙÔ˘ ÂÈı˘ÌËÙÔ‡ 70-90% (MMWR 2008;57:393-404). √È ÂΉfiÙ˜ ÙÔ˘ Pediatr Inf Dis J (Newsletter June 2008) ˘ÂÓı˘Ì›˙Ô˘Ó ˆÛÙfiÛÔ fiÙÈ Ë ÂÈÙ˘¯›· 40-50% Â›Ó·È Û οı ÂÚ›ÙˆÛË Î·Ï‡ÙÂÚË ·fi ÙÔ 0%. √È Ô‰ËÁ›Â˜ Ù˘ Committee on Infectious Diseases Ù˘ American Academy of Pediatrics (Pediatrics 2008;121:e1016-e1031) ÂÈÛËÌ·›ÓÔ˘Ó ÙË ÓÔÛËÚfiÙËÙ· Ù˘ ÁÚ›˘ ÛÙ· ·È‰È¿ Î·È Ì¿ÏÈÛÙ· ÛÙ· οو ÙˆÓ 2 ÂÙÒÓ Î·È ÂÈ̤ÓÔ˘Ó ÛÙÔÓ ÂÌ‚ÔÏÈ·ÛÌfi. √È Ô‰ËÁ›Â˜ ÂÓ·ÚÌÔÓ›˙ÔÓÙ·È Ì ÂΛӘ ÙÔ˘ CDC. √È ÂÚÈÛÛfiÙÂÚÔÈ ·ÛıÂÓ›˜ Ì ¿ÛıÌ· ‰ÂÓ ÂÌ‚ÔÏÈ¿˙ÔÓÙ·È Î·Ù¿ Ù˘ ÁÚ›˘ (MMWR 2008;57:653-6), ·Ú¿ ÙÔ fiÙÈ ÔÈ Û˘ÛÙ¿ÛÂȘ ÂÌ‚ÔÏÈ·ÛÌÔ‡ ÈÛ¯‡Ô˘Ó ·fi ÙÔ 1964. ∆· ·È‰È¿ Ì ¿ÛıÌ· ÂÌ‚ÔÏÈ¿˙ÔÓÙ·È ÏÈÁfiÙÂÚÔ, ÂÓÒ ÔÈ ËÏÈÎȈ̤ÓÔÈ Û˘ÌÌÔÚÊÒÓÔÓÙ·È ÂÚÈÛÛfiÙÂÚÔ. ∆Ô ÂÌ‚fiÏÈÔ ÁÈ· ÙË ÁÚ›Ë ÌÂÈÒÓÂÈ Ù· ÂÂÈÛfi‰È· ÈÛ¯·ÈÌ›·˜ Û ·ÛıÂÓ›˜ Ì ÛÙÂÊ·ÓÈ·›· ÓfiÛÔ Î·Ù¿ 50% (Eur Heart J 2008;29:1350-8). ™ÙË ÌÂϤÙË ·˘Ù‹ ·fi ÙË µ·ÚÛÔ‚›·, Ô Ì˯·ÓÈÛÌfi˜ ÚÔÛÙ·Û›·˜ ‰ÂÓ ‰È¢ÎÚÈÓ›ÛıËÎÂ, ˆÛÙfiÛÔ Ë ÚÔÛÙ·Û›· Ê·›ÓÂÙ·È Ó· ÂÂÎÙ›ÓÂÙ·È Î·È ¤Ú·Ó Ù˘ ÂÔ¯È΋˜ ηٷÓÔÌ‹˜ Ù˘ ÁÚ›˘. ∂Ì‚fiÏÈÔ ÁÈ· ÙË ÁÚ›Ë ÙˆÓ ÙËÓÒÓ. √È ÚÔÛ¿ıÂȘ ·Ú·ÁˆÁ‹˜ ÂÌ‚ÔÏ›ˆÓ ÁÈ· ÙËÓ ·Ó‰ËÌÈ΋ ÁÚ›Ë ÙˆÓ ÙËÓÒÓ ¤¯Ô˘Ó ‹‰Ë ·Ô‰ÒÛÂÈ. ŸÏ· Ù· ¤ˆ˜ ÙÒÚ· ÂÌ‚fiÏÈ· Â›Ó·È “prepandemic”, ÙÔ ÔÔ›Ô ÛËÌ·›ÓÂÈ fiÙÈ ·ÔÛÎÔÔ‡Ó ÛÙËÓ ÂÍ·ÛÊ¿ÏÈÛË ÌË ÂȉÈ΋˜ ÚÔÛÙ·Û›·˜ ¤ˆ˜ fiÙÔ˘ ·Ú·Û΢·Ûı› ÙÔ ÈÔ ÂȉÈÎfi ÁÈ· ÙÔ Û˘ÁÎÂÎÚÈ̤ÓÔ Û٤ϯԘ, ‰ËÏ·‰‹ ÂÚ›Ô˘ 4-6 Ì‹Ó˜ ·fi ÙËÓ ÂΉ‹ÏˆÛË Ù˘ ·Ó‰ËÌ›·˜. ™ÙËÓ ∂˘Úˆ·˚΋ ŒÓˆÛË (Reuters, 19 ª·˝Ô˘ 2008), ‡ÛÙÂÚ· ·fi ÂÈÛ‹ÁËÛË Ù˘ European Medicines Agency, ÂÁÎÚ›ıËΠÙÔ Prepandrix/GlaxoSmithKline ηٿ ÙÔ˘ ÛÙÂϤ¯Ô˘˜ H5N1. ™Â ÌÂϤÙË ·fi ÙËÓ ∞˘ÛÙÚ›· (New Engl J Med 2008;358:2753-84), ÂÌ‚fiÏÈÔ Ù˘ Baxter Ì ·‰Ú·ÓÔÔÈË̤ÓÔ Û٤ϯԘ ∞/Vietnam/1203/2004 Û 2 ‰fiÛÂȘ ÂÍ·ÛÊ¿ÏÈÛ Û ÂıÂÏÔÓÙ¤˜ ·ÓȯÓ‡ÛÈÌ· ÂÍÔ˘‰ÂÙÂÚˆÙÈο ·ÓÙÈÛÒÌ·Ù·. ∆Ô ÂÌ‚fiÏÈÔ ¶·È‰È·ÙÚÈ΋ 2008;71:324-326

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™À¡∆√ª∞ ¶∞π¢π∞∆ƒπ∫∞ ¡∂∞ ·Ú·Û΢¿˙ÂÙ·È Û ΢ÙÙ·ÚÔηÏÏȤÚÁÂȘ Î·È fi¯È Û ÁÔÓÈÌÔÔÈË̤ӷ ·˘Á¿, ¿Ú· ¤¯ÂÈ ÏÂÔÓÂÎÙ‹Ì·Ù· ·Ú·ÁˆÁ‹˜. ™ÙËÓ ∫›Ó· (Reuters Health, 3 ∞ÚÈÏ›Ô˘ 2008), ‰fiıËΠ¤ÁÎÚÈÛË Û ÎÈÓÂ˙È΋ ÂÙ·ÈÚ›· ÁÈ· ÙËÓ ·Ú·ÁˆÁ‹ ÂÌ‚ÔÏ›Ô˘ Ì ·‰Ú·ÓÔÔÈË̤ÓÔ Û٤ϯԘ H5N1 ·fi ÙÔ µÈÂÙÓ¿Ì. ™Â ÎÏÈÓÈ΋ ‰ÔÎÈÌ‹ ÌÂÙÚ‹ıËÎ·Ó Ù›ÙÏÔÈ ·ÓÙÈÛˆÌ¿ÙˆÓ Û˘Ì‚·ÙÔ› Ì ÙȘ Â˘Úˆ·˚Τ˜ Î·È ·ÌÂÚÈηÓÈΤ˜ ÚԉȷÁڷʤ˜. ™ÙÔ µÈÂÙÓ¿Ì, ¯ÒÚ· Ô˘ ¤¯ÂÈ ÏËÁ› ȉȷ›ÙÂÚ· ·fi ÙË ÓfiÛÔ, ÚÔÁÚ·ÌÌ·Ù›˙ÂÙ·È ·Ú·ÁˆÁ‹ 6.000.000 ‰fiÛÂˆÓ ÂÌ‚ÔÏ›Ô˘ ÂÙËÛ›ˆ˜ (Reuters Health, 18 ª·ÚÙ›Ô˘ 2008). ∂Ì‚fiÏÈ· ÂÓËϛΈÓ. √ ÂÌ‚ÔÏÈ·ÛÌfi˜ ÙˆÓ ÂÓËÏ›ÎˆÓ ‚Ú›ÛÎÂÙ·È Û ‚ÚÂÊÈÎfi ÛÙ¿‰ÈÔ. ™ÙȘ ∏¶∞, ÌfiÓÔ 2% ÙˆÓ ¿Óˆ ÙˆÓ 60 ÂÙÒÓ ¤¯Ô˘Ó ÂÌ‚ÔÏÈ·Ûı› ÁÈ· ¤ÚËÙ· ˙ˆÛÙ‹Ú·, ÌfiÓÔ 2% ÙˆÓ 18-64 ÂÙÒÓ Ì ÙÔ Ó¤Ô ÂÌ‚fiÏÈÔ DtaP, ÌfiÓÔ 10% ÙˆÓ Á˘Ó·ÈÎÒÓ 18-26 ÂÙÒÓ ¤¯ÂÈ ÂÌ‚ÔÏÈ·Ûı› ÁÈ· HPV Î·È ÌfiÓÔ 68% Î·È 66% ÙˆÓ ¿Óˆ ÙˆÓ 65 ÂÙÒÓ ¤¯Ô˘Ó ÂÌ‚ÔÏÈ·Ûı› ÁÈ· ÁÚ›Ë Î·È Ó¢ÌÔÓÈfiÎÔÎÎÔ (WebMD Health News, 14 π·ÓÔ˘·Ú›Ô˘ 2008).

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™Â ÚfiÛÊ·ÙË ·Ó·ÎÔ›ÓˆÛ‹ ÙÔ˘, ÙÔ CDC Û˘ÓÈÛÙ¿ 1 ‰fiÛË ÂÌ‚ÔÏ›Ô˘ (Zostavax) ÁÈ· ÙÔÓ ¤ÚËÙ· ˙ˆÛÙ‹Ú· Û fiÏÔ˘˜ ÙÔ˘˜ ¿Óˆ ÙˆÓ 60 ÂÙÒÓ, ·ÎfiÌË ÎÈ ·Ó ¤¯Ô˘Ó ·Ó·ÌÓËÛÙÈÎfi ¤ÚËÙ· ˙ˆÛÙ‹Ú· (MMWR 2008;57:1-30). ∂Ì‚fiÏÈÔ ÁÈ· ÙÔ Î¿ÓÈÛÌ· Î·È ÂÌ‚fiÏÈÔ ÁÈ· ÙËÓ ˘¤ÚÙ·ÛË. ™˘˙¢Á̤ÓÔ ÂÌ‚fiÏÈÔ ÓÈÎÔÙ›Ó˘ (NicVAX®/Nabi Biopharmaceuticals) Ô˘ ‚·Û›˙ÂÙ·È Û ·ÓÙÈÛÒÌ·Ù· Ô˘ ‰ÂÛÌÂ‡Ô˘Ó ÙË ÓÈÎÔÙ›ÓË Î·È ÂÈ‚Ú·‰‡ÓÔ˘Ó ÙËÓ Â›ÛÔ‰fi Ù˘ ÛÙÔÓ ÂÁΤʷÏÔ Î·È ÌÔÚ› Ó· ‚ÔËı‹ÛÂÈ ÙÔ˘˜ ηÓÈÛÙ¤˜ Ó· Îfi„Ô˘Ó ÙÔ Î¿ÓÈÛÌ· Î·È Ó· ÌËÓ ÙÔ Í·Ó·Ú¯›ÛÔ˘Ó (11Ô Annual Conference on Vaccine Research, µ·ÏÙÈÌfiÚË, MD, 5-7 ª·˝Ô˘ 2008). ∂Ì‚fiÏÈÔ Ù˘ ÂÙ·ÈÚ›·˜ Cytos ·fi ÙË ∑˘Ú›¯Ë (CYT006-AngQb) Ô˘ ‚·Û›˙ÂÙ·È Û ·ÓÙÈÛÒÌ·Ù· ηٿ Ù˘ ·ÁÁÂÈÔÙÂÓÛ›Ó˘ ππ ·ԉ›¯ıËΠ·ÔÙÂÏÂÛÌ·ÙÈÎfi ηٿ Ù˘ ˘¤ÚÙ·Û˘ Ì ÂÍ¿ÌËÓË ÂÚ›Ô˘ ÚÔÛÙ·Û›· (Lancet 2008;371:821-7). ¶·Ú¿ ÙȘ ‡ÏÔÁ˜ ÂÈÊ˘Ï¿ÍÂȘ, ÔÈ ÂÌ‚ÔÏÈ·ÛÌÔ› ‰Â›¯ÓÔ˘Ó Ó· ¤¯Ô˘Ó ¿ÚÂÈ ‰ÚfiÌÔ˘˜ ¤Íˆ ·fi ÙȘ Û˘Ó‹ıÂȘ ÏÔÈÌÒÍÂȘ ÙˆÓ ‚ÚÂÊÒÓ Î·È ÓË›ˆÓ.

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H ÈÛÙÔÛÂÏ›‰· ÙÔ˘ µ·ÛÈÏÈÎÔ‡ ∫ÔÏÂÁ›Ô˘ ¶·È‰È·ÙÚÈ΋˜ Î·È ¶·È‰È΋˜ ÀÁ›·˜ ∫. ™ÙÂÊ·Ó›‰Ë˜

The web page of the Royal College of Paediatrics and Child Health (RCPCH) C. Stefanidis ¶ÚÈÓ ·fi 80 ¯ÚfiÓÈ·, ÌÈ· ÌÈÎÚ‹ ÔÌ¿‰· ·È‰È¿ÙÚˆÓ ·fi ‰È·ÊÔÚÂÙÈΤ˜ fiÏÂȘ ÙÔ˘ ∏ӈ̤ÓÔ˘ µ·ÛÈÏ›Ԣ ‰ËÌÈÔ‡ÚÁËÛ·Ó ÙË µÚÂÙ·ÓÈ΋ ¶·È‰È·ÙÚÈ΋ ∂Ù·ÈÚ›·. ™ÎÔfi˜ Ù˘ ∂Ù·ÈÚ›·˜ ‹Ù·Ó Ë ·Ó¿Ù˘ÍË Ù˘ ¶·È‰È·ÙÚÈ΋˜ Î·È Ë ‚ÂÏÙ›ˆÛË Ù˘ Û˘ÓÂÚÁ·Û›·˜ ÙˆÓ ·È‰È¿ÙÚˆÓ. ™Ù· ÂfiÌÂÓ· ¯ÚfiÓÈ·, Ô ·ÚÈıÌfi˜ ÙˆÓ ÌÂÏÒÓ Ù˘ ∂Ù·ÈÚ›·˜ ·˘Í‹ıËÎÂ Î·È ÔÈ ‰Ú·ÛÙËÚÈfiÙËÙ¤˜ Ù˘ ÔÏÏ·Ï·ÛÈ¿ÛÙËηÓ. ŸÌˆ˜, ÙfiÛÔ ÁÈ· ÙËÓ Âȉ›Î¢ÛË ÛÙËÓ ¶·È‰È·ÙÚÈ΋, fiÛÔ Î·È ÁÈ· ÙȘ ÂÍÂÙ¿ÛÂȘ ÂȉÈÎfiÙËÙ·˜, ‹Ù·Ó ˘‡ı˘ÓÔ ÙÔ µ·ÛÈÏÈÎfi π·ÙÚÈÎfi ∫ÔϤÁÈÔ. ⁄ÛÙÂÚ· ·fi Ì·ÎÚfi¯ÚÔÓ˜ ÚÔÛ¿ıÂȘ Î·È Û˘˙ËÙ‹ÛÂȘ ¤ÁÈÓ ·Ô‰ÂÎÙfi fiÙÈ Ë ¶·È‰È·ÙÚÈ΋ ‹Ù·Ó ÌÈ· Â·ÚÎÒ˜ ÌÂÁ¿ÏË Î·È ·ÚÎÂÙ¿ ÛËÌ·ÓÙÈ΋ ÂȉÈÎfiÙËÙ· ÁÈ· Ó· ¤¯ÂÈ ÙÔ ·˘ÙfiÓÔÌÔ ‰ÈÎfi Ù˘ ∫ÔϤÁÈÔ, ÁÂÁÔÓfi˜ Ô˘ ı· Ù˘ ¤‰ÈÓ ÙË ‰˘Ó·ÙfiÙËÙ· Ó· ¤¯ÂÈ Ô˘ÛÈ·ÛÙÈÎfi ÚfiÏÔ ÛÙËÓ ÂÎ·›‰Â˘ÛË ÛÙËÓ ¶·È‰È·ÙÚÈ΋ Î·È ÛÙË Û˘Ó¯È˙fiÌÂÓË ÂÎ·›‰Â˘ÛË ÙˆÓ ·È‰È¿ÙÚˆÓ. ŒÙÛÈ, ÙÔ 1996 Ô Ù›ÙÏÔ˜ ÙÔ˘ µ·ÛÈÏÈÎÔ‡ ∫ÔÏÂÁ›Ô˘ ÂίˆÚ‹ıËΠÛÙË µÚÂÙ·ÓÈ΋ ¶·È‰È·ÙÚÈ΋ ∂Ù·ÈÚ›·. ™ÙȘ ̤Ú˜ Ì·˜, ÙÔ µ·ÛÈÏÈÎfi ∫ÔϤÁÈÔ ¶·È‰È·ÙÚÈ΋˜ Î·È ¶·È‰È΋˜ ÀÁ›·˜ (RCPCH) ¤¯ÂÈ ÂÚÈÛÛfiÙÂÚ· ·fi 9.000 ̤ÏË. Œ¯ÂÈ ÙËÓ Â˘ı‡ÓË Ù˘ Â›‚Ï„˘ Ù˘ ÂÎ·›‰Â˘Û˘ ÛÙËÓ ¶·È‰È·ÙÚÈ΋ Î·È ÙˆÓ ÂÍÂÙ¿ÛÂˆÓ Ù˘ ÂȉÈÎfiÙËÙ·˜. ™˘ÓÙÔÓ›˙ÂÈ ÙËÓ ·È‰È·ÙÚÈ΋ ¤Ú¢ӷ, ÔÚÁ·ÓÒÓÂÈ ÂÈÛÙËÌÔÓÈΤ˜ ËÌÂÚ›‰Â˜ Î·È Û˘Ó¤‰ÚÈ· Î·È ·Ú¿ÁÂÈ ‰ËÌÔÛȇÛÂȘ, fi¯È ÌfiÓÔ ÁÈ· Ù· ̤ÏË ÙÔ˘, ·ÏÏ¿ Î·È ÁÈ· fiÛÔ˘˜ ·Û¯ÔÏÔ‡ÓÙ·È Ì ¿ÏÏ· Û˘Ó·Ê‹ Â·ÁÁ¤ÏÌ·Ù· ˘Á›·˜. √È ÂÚÈÛÛfiÙÂÚ˜ ·fi ·˘Ù¤˜ ÙȘ ‰ËÌÔÛȇÛÂȘ Â›Ó·È ÂχıÂÚ˘ ÚfiÛ‚·Û˘ ÛÙËÓ ÈÛÙÔÛÂÏ›‰· ÙÔ˘ RCPCH Î·È ·ÊÔÚÔ‡Ó ÙËÓ ·È‰È·ÙÚÈ΋ ¤Ú¢ӷ Î·È ÂÎ·›‰Â˘ÛË.

¡ÂÊÚÔÏÔÁÈÎfi ∆Ì‹Ì·, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡” AÏÏËÏÔÁÚ·Ê›·: ∫ˆÓÛÙ·ÓÙ›ÓÔ˜ ™ÙÂÊ·Ó›‰Ë˜ stefanid@hol.gr ¡ÂÊÚÔÏÔÁÈÎfi ∆Ì‹Ì·, ¡ÔÛÔÎÔÌÂ›Ô ¶·›‰ˆÓ “¶. & ∞. ∫˘ÚÈ·ÎÔ‡”

Division of Nephrology, “P. & ∞. ∫yriakou” Children’s Hospital, Athens, Greece Correspondence: Constantinos Stefanidis stefanid@hol.gr Division of Nephrology, “P. & ∞. ∫yriakou” Children’s Hospital, Athens, Greece

∏ ·Ú¯È΋ ÈÛÙÔÛÂÏ›‰· ÙÔ˘ µ·ÛÈÏÈÎÔ‡ ∫ÔÏÂÁ›Ô˘ ¶·È‰È·ÙÚÈ΋˜ Î·È ¶·È‰È΋˜ ÀÁ›·˜ (RCPCH) - http://www.rcpch.ac.uk ™ÙËÓ ÈÛÙÔÛÂÏ›‰· ·˘Ù‹ ÂÚÈÏ·Ì‚¿ÓÔÓÙ·È ÔÈ Ó¤Â˜ ‰ËÌÔÛȇÛÂȘ ÙÔ˘ RCPCH, ¯Ú‹ÛÈ̘ ÏËÚÔÊÔڛ˜ ÁÈ· Ù· ̤ÏË Î·È ÚfiÛÊ·Ù· ·È‰È·ÙÚÈο Ó¤· ·fi Ù· ̤۷ Ì·˙È΋˜ ÂÓË̤ڈÛ˘. ªÂ ÂӉȷʤÚÔÓ Â›‰· ÙȘ ı¤ÛÂȘ ÙÔ˘ ∫ÔÏÂÁ›Ô˘ Û¯ÂÙÈο Ì ÙȘ ΢‚ÂÚÓËÙÈΤ˜ ÚÔÙ¿ÛÂȘ ÁÈ· ÙËÓ ·ÓÙÈÌÂÙÒÈÛË Ù˘ ·È‰È΋˜ ·¯˘Û·ÚΛ·˜. ∆ÔÓ›˙ÔÓÙ·È ÔÈ ¿ÌÂÛ˜ Î·È Ì·ÎÚÔ¯ÚfiÓȘ Û˘Ó¤ÂȘ Ù˘ ·¯˘Û·ÚΛ·˜ Î·È Ë ÛËÌ·Û›· Ù˘ ÚÔ·ÁˆÁ‹˜ ÙÔ˘ ÌËÙÚÈÎÔ‡ ıËÏ·ÛÌÔ‡ ÁÈ· ÙË ÚfiÏË„‹ Ù˘. ∂›Û˘, ·Ó·Ê¤ÚÂÙ·È Ë ÈÛÙÔÛÂÏ›‰· Ô˘ ÂÚȤ¯ÂÈ ÙȘ ÚÔÙ¿ÛÂȘ ÁÈ· ÙË ÛÙÚ·ÙËÁÈ΋ Ì›ˆÛ˘ Ù˘ ·È‰È΋˜ ·¯˘Û·ÚΛ·˜: http://www.dh.gov.uk/en/ Publications andstatistics/Publications/Publications PolicyAndGuidance/ DH_082378. ™ÙËÓ ÈÛÙÔÛÂÏ›‰· http://www.rcpch.ac.uk/Training/ Competency-Frameworks ÂÚȤ¯ÔÓÙ·È ÛÙÔȯ›· ÁÈ· ÙȘ ··Ú·›ÙËÙ˜ ÈηÓfiÙËÙ˜ Ô˘ Ú¤ÂÈ Ó· ¤¯Ô˘Ó ÔÈ ÂȉÈ΢fiÌÂÓÔÈ ÛÙËÓ ¶·È‰È·ÙÚÈ΋ ‡ÛÙÂÚ· ·fi οı Â›Â‰Ô ÂÎ·›‰Â˘Û˘. °È· ÙÔ ÚÒÙÔ Â›Â‰Ô (3 ÚÒÙ· ¯ÚfiÓÈ· ÂȉÈÎfiÙËÙ·˜) Ù˘ ‚·ÛÈ΋˜ ÂÎ·›‰Â˘Û˘, ÂÎÙfi˜ ·fi ÙȘ ÎÏÈÓÈΤ˜ ‰ÂÍÈfiÙËÙ˜, ‰›ÓÂÙ·È È‰È·›ÙÂÚË ¤ÌÊ·ÛË ÛÙËÓ Î·Ù·ÓfiËÛË Ù˘ Û˘Ó·ÈÛıËÌ·ÙÈ΋˜, ÎÔÈÓˆÓÈ΋˜ Î·È ÁÓˆÛÙÈ΋˜ ·Ó¿Ù˘Í˘ ÙÔ˘ ·È‰ÈÔ‡. π‰È·›ÙÂÚË ¤ÌÊ·ÛË ‰›ÓÂÙ·È Â›Û˘ ÛÙËÓ ·ÍÈÔÏfiÁËÛË Î·È ÙËÓ ·ÓÙÈÌÂÙÒÈÛË ÙˆÓ ‰È·Ù·Ú·¯ÒÓ Ù˘ ·‡ÍËÛ˘ Î·È ıÚÂÙÈ΋˜ ¶·È‰È·ÙÚÈ΋ 2008;71:327-329

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¡∂∞ ∞¶√ ∆√ ¢π∞¢π∫∆À√ ηٿÛÙ·Û˘ ÙˆÓ ·È‰ÈÒÓ. ∂ÈϤÔÓ, ÙÔÓ›˙ÂÙ·È Ë ÛËÌ·Û›· ÙˆÓ ÂÈÎÔÈÓˆÓÈ·ÎÒÓ ‰ÂÍÈÔÙ‹ÙˆÓ ÙÔ˘ ·È‰È¿ÙÚÔ˘ Î·È ÙÔ˘ ËÁÂÙÈÎÔ‡ ÙÔ˘ ÚfiÏÔ˘ ÛÙËÓ ÔÌ¿‰· ÂÈÛÙËÌfiÓˆÓ ÌÂ Û˘Ó·Ê‹ Â·ÁÁ¤ÏÌ·Ù· ˘Á›·˜. ∆¤ÏÔ˜, ·Ó·Ê¤ÚÔÓÙ·È ÔÈ ··Ú·›ÙËÙ˜ ‰ÂÍÈfiÙËÙ˜ Û¯ÂÙÈο Ì ÙËÓ ÂÊË‚È΋ È·ÙÚÈ΋ Ô˘ Ú¤ÂÈ Ó· ·ÔÎÙ‹ÛÂÈ Ô ÂȉÈ΢fiÌÂÓÔ˜ ÛÙÔ Ù¤ÏÔ˜ Ù˘ ÂȉÈÎfiÙËÙ·˜. °È· ÙÔ ‰Â‡ÙÂÚÔ Â›Â‰Ô Ù˘ ÂÎ·›‰Â˘Û˘ (4Ô Î·È 5Ô ¯ÚfiÓÔ ÂȉÈÎfiÙËÙ·˜), ÔÈ ··ÈÙ‹ÛÂȘ Â›Ó·È ÂÚÈÛÛfiÙÂÚ˜ Î·È ÔÈ ··ÈÙÔ‡ÌÂÓ˜ ‰ÂÍÈfiÙËÙ˜ ÈÔ ÂÍÂȉÈÎÂ˘Ì¤Ó˜. ∆¤ÏÔ˜, ÂӉȷʤÚÔÓ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÔÈ ÚÔÙ¿ÛÂȘ ÁÈ· ÙÔ ÙÚ›ÙÔ Â›Â‰Ô Ù˘ ÂÎ·›‰Â˘Û˘ (˘ÔÂȉÈÎfiÙËÙ˜). ∞Ó·Ï˘ÙÈο ·Ó·Ê¤ÚÔÓÙ·È ÔÈ ‰ÂÍÈfiÙËÙ˜ Ô˘ Ú¤ÂÈ Ó· ·ÔÎÙËıÔ‡Ó ÛÙÔ Ù¤ÏÔ˜ Ù˘ ÂÍÂȉ›Î¢Û˘ ÛÙËÓ: ∫ÔÈÓˆÓÈ΋ ¶·È‰È·ÙÚÈ΋, ¶·È‰È΋ æ˘¯È΋ ÀÁ›·, ∞ÏÏÂÚÁÈÔÏÔÁ›·, ∂Ó‰ÔÎÚÈÓÔÏÔÁ›·, °·ÛÙÚÔÂÓÙÂÚÔÏÔÁ›·, ∞ÈÌ·ÙÔÏÔÁ›·, √ÁÎÔÏÔÁ›·, ∫·Ú‰ÈÔÏÔÁ›·, §ÔÈÌÒ‰Ë NÔÛ‹Ì·Ù·, ¡ÂÔÁÓÔÏÔÁ›·, ¡Â˘ÚÔÏÔÁ›·, ¡ÂÊÚÔÏÔÁ›·, ¶Ó¢ÌÔÓÔÏÔÁ›· Î·È ƒÂ˘Ì·ÙÔÏÔÁ›·.

∏ ÈÛÙÔÛÂÏ›‰· ÙÔ˘ ∂ıÓÈÎÔ‡ µÚÂÙ·ÓÈÎÔ‡ ¶·È‰È·ÙÚÈÎÔ‡ ™˘ÓÙ·ÁÔÏÔÁ›Ô˘ http://www.rcpch.ac.uk/Publications/bnfc ∏ ¤Î‰ÔÛË ·˘Ù‹ Â›Ó·È ÙÔ ·ÔÙ¤ÏÂÛÌ· Ù˘ Û˘ÓÂÚÁ·Û›·˜ ÙÔ˘ µ·ÛÈÏÈÎÔ‡ ∫ÔÏÂÁ›Ô˘ ¶·È‰È·ÙÚÈ΋˜ Î·È ¶·È‰È΋˜ ÀÁ›·˜ Ì ÙÔ µÚÂÙ·ÓÈÎfi π·ÙÚÈÎfi ™‡ÏÏÔÁÔ, ÙË µ·ÛÈÏÈ΋ º·Ú̷΢ÙÈ΋ ∂Ù·ÈÚ›· Î·È ÙËÓ √Ì¿‰· º·ÚÌ·ÎÔÔÈÒÓ ¡ÂÔÁÓÈ΋˜ Î·È ¶·È‰È΋˜ ∏ÏÈΛ·˜. √È ÏËÚÔÊÔڛ˜ ÙÔ˘ ™˘ÓÙ·ÁÔÏÔÁ›Ô˘ ¤¯Ô˘Ó ·ÍÈÔÏÔÁËı› Ì ۇÁ¯ÚÔÓ˜ ηÙ¢ı˘ÓÙ‹ÚȘ Ô‰ËÁ›Â˜ Î·È Ì ÙË ÁÓˆÌÔ‰fiÙËÛË ÂÓfi˜ ‰ÈÎÙ‡Ô˘ ÂÌÂÈÚÔÁÓˆÌfiÓˆÓ. ∆Ô ∂ıÓÈÎfi µÚÂÙ·ÓÈÎfi ¶·È‰È·ÙÚÈÎfi ™˘ÓÙ·ÁÔÏfiÁÈÔ ‰È·Ù›ıÂÙ·È Â›Û˘ Î·È ÁÈ· ËÏÂÎÙÚÔÓÈÎÔ‡˜ ˘ÔÏÔÁÈÛÙ¤˜ ÙÛ¤˘ (PDA).

¶›Ó·Î·˜ 1. ∂ÈÏÂÁ̤Ó˜ ‰ËÌÔÛȇÛÂȘ ÙÔ˘ µ·ÛÈÏÈÎÔ‡ ∫ÔÏÂÁ›Ô˘ ¶·È‰È·ÙÚÈ΋˜ Î·È ¶·È‰È΋˜ ÀÁ›·˜ 1. Immunisation of the Immunocompromised Management of severe malnutrition: a manual for physicians and other senior health workers 2. Paediatric Training Handbook: 2nd edition 3. Standards for Development of Clinical Guidelines in Paediatrics and Child Health: 3rd edition 4. Strengthening the Care of Children in the Community 5. Sudden Unexpected Death in Infancy 6. Training Needs in Community Paediatrics 7. Training Paediatricians of the Future 8. Vision and Values 9. Withholding or Withdrawing Life Sustaining Treatment in Children: A Framework for Practice

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∏ ÈÛÙÔÛÂÏ›‰· ÙˆÓ ‰ËÌÔÛȇÛÂˆÓ ÙÔ˘ µ·ÛÈÏÈÎÔ‡ ∫ÔÏÂÁ›Ô˘ ¶·È‰È·ÙÚÈ΋˜ Î·È ¶·È‰È΋˜ ÀÁ›·˜ - http://www.rcpch.ac.uk/publications ™ÙËÓ ÈÛÙÔÛÂÏ›‰· ·˘Ù‹ ˘¿Ú¯Ô˘Ó ·Ú·ÔÌ¤˜ ÁÈ· 394 ‰ËÌÔÛȇÛÂȘ ÙÔ˘ ∫ÔÏÂÁ›Ô˘, ÁÂÁÔÓfi˜ Ô˘ ‰Â›¯ÓÂÈ ÙËÓ ·Ú·ÁˆÁÈÎfiÙËÙ· Ù˘ ∂ÎÙÂÏÂÛÙÈ΋˜ ∂ÈÙÚÔ‹˜, fiÏˆÓ ÙˆÓ ÂÓÂÚÁÒÓ ÌÂÏÒÓ Î·È Ê˘ÛÈο ÙˆÓ ÂÚ›Ô˘ 100 ˘·ÏÏ‹ÏˆÓ ÙÔ˘ ∫ÔÏÂÁ›Ô˘. √È ÓÂÒÙÂÚÔÈ Û˘Ó¿‰ÂÏÊÔÈ ı· ‚ÚÔ˘Ó ¯Ú‹ÛÈÌË ÙË ‰ËÌÔÛ›Â˘ÛË ÁÈ· ÙË ÛÙ·‰ÈÔ‰ÚÔÌ›· ÛÙËÓ ¶·È‰È·ÙÚÈ΋ (Careers in Paediatrics) Î·È ÁÈ· ÙËÓ ·Î·‰ËÌ·˚΋ ÎÏÈÓÈ΋ Ú¿ÍË (Clinical Academics). π‰È·›ÙÂÚÔ ÂӉȷʤÚÔÓ ·ÚÔ˘ÛÈ¿˙Ô˘Ó ÔÈ ‰ËÌÔÛȇÛÂȘ Ô˘ ·Ó·Ê¤ÚÔÓÙ·È ÛÙÔÓ ¶›Ó·Î· 1 Î·È ÔÈ ÎÏÈÓÈΤ˜ Ô‰ËÁ›Â˜ ÁÈ· ‰È¿ÊÔÚ· ÚÔ‚Ï‹Ì·Ù· Ù˘ ·È‰È΋˜ Î·È ÂÊË‚È΋˜ ËÏÈΛ·˜ (¶›Ó·Î·˜ 2). µÚ‹Î· ÙȘ ÏËÚÔÊÔڛ˜ ·˘Ù¤˜ ·ÚÎÂÙ¿ ¯Ú‹ÛÈ̘ Î·È ÂÏ›˙ˆ fiÙÈ ı· Û·˜ ÂӉȷʤÚÔ˘Ó.

¶›Ó·Î·˜ 2. ∂ÈÏÂÁ̤Ó˜ ‰ËÌÔÛȇÛÂȘ ÎÏÈÓÈÎÒÓ Ô‰ËÁÈÒÓ ÙÔ˘ µ·ÛÈÏÈÎÔ‡ ∫ÔÏÂÁ›Ô˘ ¶·È‰È·ÙÚÈ΋˜ Î·È ¶·È‰È΋˜ ÀÁ›·˜ ÁÈ· ‰È¿ÊÔÚ· ÚÔ‚Ï‹Ì·Ù· Ù˘ ·È‰È΋˜ Î·È ÂÊË‚È΋˜ ËÏÈΛ·˜ 1. Acute Breathing Difficulty - Management of Children with Acute Breathing Difficulty 2. Acute Pain - Recognition and Assessment of Acute Pain in Children 3. ADHD - Assessment and Treatment of Attention Deficit and Hyperkinetic Disorders in Children 4. Asthma - Management of Asthma 5. Cancer - Survivors of Childhood Cancer 6. Cystic Fibrosis - Performance of the Sweat Test for the Investigation of Cystic Fibrosis in the UK 7. Decreased Consciousness 8. Dental Caries - Preventing Dental Caries in Children at High Caries 9. Depression in Children 10. Diabetes - Diagnosis and Management of Type I Diabetes in Children and Young People 11. Diabetes - Management of Diabetes in Children and Young People 12. Diarrhoea - Management of Children Presenting to Hospital with Diarrhoea, with or without Vomiting 13. Epilepsy (SIGN) - Diagnosis and Management of Epilepsies in Children and Young People: A National Clinical Guideline 14. Head Injury - Early Management of Patients with a Head Injury 15. Head Injury - Head Injury: triage, assessment, investigation and early management of head injury in infants, children and young people 16. Infectious Diseases - Guidelines on the Management of Communicable Diseases in Schools 17. Milk Banking - Milk Banking 18. Mouth care for children and young people with cancer 19. Neonatal RDS - Management of Neonatal Respiratory Distress Syndrome 20. Obesity - Management of Obesity in Children and Young People 21. Otitis Media - Diagnosis and Management of Otitis Media in Primary Care 22. Referral for Suspected Cancer 23. Pleural Infection - Management of Pleural Infection in Children 24. Pneumonia - Management of Community Acquired Pneumonia in Childhood 25. Post Seizure - Post Seizure Management 26. Post Traumatic Stress Disorder 27. Sedation - Safe Sedation of Children Undergoing Diagnostic and Therapeutic Procedures 28. Self Harm - The short-term physical and psychological management and secondary prevention of self-harm in primary and secondary care 29. Screening and Treatment of Retinopathy and Prematurity 30. Stroke - Diagnosis and Management of Stroke in Children 31. UTI - Diagnosis, Treatment and Evaluation of the Initial Urinary Tract Infection in Febrile Infants and Young Children

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∫§π¡π∫√ ∫√Àπ∑ ∫ÏÈÓÈÎfi QUIZ ∞¶∞¡∆∏™∏ ¢È¿ÁÓˆÛË: ÃÚfiÓÈ· ÛÎÏËÚ˘ÓÙÈ΋ ÔÛÙÂÔÌ˘ÂÏ›Ùȉ· Ù‡Ô˘ Garré ∏ Ú·È‚fiÙËÙ· Ù˘ ÎÓ‹Ì˘, ÁÈ· ¤Ó· ‚Ú¤ÊÔ˜ 16 ÌËÓÒÓ, Â›Ó·È Ê˘ÛÈÔÏÔÁÈ΋ Î·È ·Ó·ÌÂÓfiÌÂÓË, Û‡Ìʈӷ Ì ٷ ‰Â‰Ô̤ӷ Ù˘ ‚È‚ÏÈÔÁÚ·Ê›·˜ (1). ™˘ÓÂÒ˜, Ë Â˘ı˘ÁÚ¿ÌÌÈÛË Ù˘ ‰ÂÍÈ¿˜ ÎÓ‹Ì˘ ‹Ù·Ó ÂΛÓË Ô˘ ÚÔοÏÂÛ ·Ú¯Èο ÙÔ ÂӉȷʤÚÔÓ Ì·˜ Î·È Ô‰‹ÁËÛ ÙË ‰È·ÁÓˆÛÙÈ΋ Ì·˜ ÛΤ„Ë ÁÈ· ÙËÓ ·Ó·˙‹ÙËÛË Ù˘ ηٿÏÏËÏ˘ ıÂÚ·¢ÙÈ΋˜ χÛ˘. ∏ ¯ÚfiÓÈ· ÛÎÏËÚ˘ÓÙÈ΋ ÔÛÙÂÔÌ˘ÂÏ›Ùȉ· Ù‡Ô˘ Garré Â›Ó·È ÌÈ· ÓfiÛÔ˜ Ô˘ ÚÔÛ‚¿ÏÏÂÈ ·È‰È¿ Î·È Ó·ÚÔ‡˜ ÂÓ‹ÏÈΘ. ∏ ÂÌÊ¿ÓÈÛ‹ Ù˘ Û ‚Ú¤ÊË ıˆÚÂ›Ù·È ÂÍ·ÈÚÂÙÈο Û¿ÓÈ· (2). ™˘¯ÓfiÙÂÚ˜ ÂÓÙÔ›ÛÂȘ Ù˘ ÂÚÈÁÚ¿ÊÔÓÙ·È Û ÌÂٷʇÛÂȘ ÙˆÓ Ì·ÎÚÒÓ ÔÛÙÒÓ, ·ÏÏ¿ Î·È ÛÙÔ ÔÛÙÔ‡Ó Ù˘ οو ÁÓ¿ıÔ˘ (3). ∏ ÎÏÈÓÈ΋ ÂΉ‹ÏˆÛË ¯·Ú·ÎÙËÚ›˙ÂÙ·È ·fi ‹È· ÂÓԯϋ̷ٷ, ΢ڛˆ˜ ‰È·Ï›ÔÓÙ· Î·È Ó˘ÎÙÂÚÈÓ¿ ¿ÏÁË, ÙÔÈ΋ ¢·ÈÛıËÛ›· Î·È ÂÏ·ÊÚfi Ô›‰ËÌ·. √ ˘ÔÂÚÈÔÛÙÈÎfi˜ Û¯ËÌ·ÙÈÛÌfi˜ Ó¤Ô˘ ÔÛÙÔ‡, Ë ÛÎÏ‹Ú˘ÓÛË ÙÔ˘ ÊÏÔÈÔ‡ Î·È Ë ·‡ÍËÛË ÙˆÓ ‰È·ÛÙ¿ÛÂˆÓ ÙÔ˘ ÔÛÙÔ‡ ÛÙËÓ ÂÛÙ›· Ù˘ ‚Ï¿‚˘ Â›Ó·È Ù· ·ıÔÁÓˆÌÔÓÈο ÛËÌ›· Ô˘ ¯·Ú·ÎÙËÚ›˙Ô˘Ó ÙË ÓfiÛÔ ·fi ÙËÓ ÚÒÙË ÎÈfiÏ·˜ ‰ËÌÔÛ›Â˘Û‹ Ù˘ ·fi ÙÔÓ Garré ÛÙ· 1893. √ ·ÎÙÈÓÔÏÔÁÈÎfi˜ ¤ÏÂÁ¯Ô˜ Û˘Ó‹ıˆ˜ ·Ó·‰ÂÈÎÓ‡ÂÈ Ù· ¯·Ú·ÎÙËÚÈÛÙÈο ·˘Ù¿ Î·È ı¤ÙÂÈ ÙȘ ‚¿ÛÂȘ Ù˘ ‰È¿ÁÓˆÛ˘ (4). TÔ ÔÛÙÈÎfi ÛÈÓıËÚÔÁÚ¿ÊËÌ· Ì ڷ‰ÈÂÓÂÚÁfi Tc99 ·ÔηχÙÂÈ Û˘Ó‹ıˆ˜ ·˘ÍË̤ÓÔ ÌÂÙ·‚ÔÏÈÛÌfi ·ÓÙ›ÛÙÔȯ· Ì ÙËÓ ÔÛÙÈ΋ ‚Ï¿‚Ë. ∏ Ì·ÁÓËÙÈ΋ ÙÔÌÔÁÚ·Ê›· ·Ó·‰ÂÈÎÓ‡ÂÈ, ÂÎÙfi˜ ·fi ÙË ÛÎÏ‹Ú˘ÓÛË ÙÔ˘ ÊÏÔÈÔ‡, ·ÏÏÔÈÒÛÂȘ ÛÙÔÓ ÔÛÙÈÎfi Ì˘ÂÏfi. ∏ ‰È·ÊÔÚÈ΋ ‰È¿ÁÓˆÛË ÔÊ›ÏÂÈ Ó· Á›ÓÂÈ ·fi ·ıÔÏÔÁÈΤ˜ ηٷÛÙ¿ÛÂȘ Ì ·ÚfiÌÔÈ· ÎÏÈÓÈ΋ ÂÈÎfiÓ· Î·È ·ÂÈÎÔÓÈÛÙÈ΋ ÛËÌÂÈÔÏÔÁ›·. ¶·ı‹ÛÂȘ, fiˆ˜ Ë ÓfiÛÔ˜ ÙÔ˘ Caffey, ÙÔ ÔÛÙÂÔÂȉ¤˜ ÔÛÙ¤ˆÌ· Î·È ÙÔ Î·ÏfiËı˜ ÔÛÙÂÔ‚Ï¿Ûو̷, ·ÏÏ¿ Î·È ¿ÏϘ ÏÈÁfiÙÂÚÔ Î·ÏÔ‹ıÂȘ, fiˆ˜ ÙÔ Û¿ÚΈ̷ Ewing, ¯ÚÂÈ¿˙ÂÙ·È Î¿ı ÊÔÚ¿ Ó· ·ÔÎÏÂÈÛÙÔ‡Ó ÚÈÓ ·fi ÙËÓ ÂÊ·ÚÌÔÁ‹ ÔÔÈ·Û‰‹ÔÙ ıÂÚ·¢ÙÈ΋˜ ·ÓÙÈÌÂÙÒÈÛ˘ (2-6). ∏ ÓfiÛÔ˜ ÙÔ˘ Caffey ÂÓÙÔ›˙ÂÙ·È ÛÙÔ ÔÛÙÔ‡Ó Ù˘ οو ÁÓ¿ıÔ˘, ·ÏÏ¿ ÚÔÛ‚¿ÏÏÂÈ Û˘Ó‹ıˆ˜ ÌÈÎÚfiÙÂÚ˜ ËÏÈ˘. ™ÙÔ ÔÛÙÂÔÂȉ¤˜ ÔÛÙ¤ˆÌ· Î·È ÛÙÔ Î·ÏfiËı˜ ÔÛÙÂÔ‚Ï¿Ûو̷, ÙˆÓ ÔÔ›ˆÓ Ë ÂÓÙfiÈÛË ·ÊÔÚ¿ Û˘Ó‹ıˆ˜ ÙË ‰È¿Ê˘ÛË ÙˆÓ Ì·ÎÚÒÓ ÔÛÙÒÓ, ˘¿Ú¯ÂÈ Ï˘ÙÈ΋ ‚Ï¿‚Ë (“ʈÏ¿”) ÛÙÔ Î¤ÓÙÚÔ Ù˘ ÛÎÏ‹Ú˘ÓÛ˘ ÙÔ˘ ÔÛÙÈÎÔ‡ ÊÏÔÈÔ‡. ∆· ¤ÓÙÔÓ· ÎÏÈÓÈο Î·È ·ÂÈÎÔÓÈÛÙÈο Â˘Ú‹Ì·Ù·, Ì ÙËÓ ·˘ÍË̤ÓË ·Ú·ÁˆÁ‹ Ó¤Ô˘ ÔÛÙÔ‡ (“ˆ˜ ÊÏÔ‡‰· ÎÚÂÌÌ˘‰ÈÔ‡”)

Paediatriki 2008;71:323,330

Î·È ÙÔÓ ·˘ÍË̤ÓÔ ÌÂÙ·‚ÔÏÈÛÌfi ÛÙÔ ›‰ÈÔ ÙÔ ÚÔۂ‚ÏË̤ÓÔ ÔÛÙÔ‡Ó, ·ÏÏ¿ Î·È ÛÙÔ˘˜ ÂÚÈ‚¿ÏÏÔÓÙ˜ Ì·Ï·ÎÔ‡˜ ÈÛÙÔ‡˜, ı¤ÙÔ˘Ó ÙȘ ˘Ô„›Â˜ ‡·Ú͢ ηÎÔ‹ıÔ˘˜ ÓfiÛÔ˘ (Û¿ÚΈ̷ Ewing), ̤¯ÚÈ ÙËÓ ÂȂ‚·›ˆÛ‹ ÙÔ˘˜ Ì ÙËÓ ÈÛÙÔ·ıÔÏÔÁÈ΋ ÂͤٷÛË Î·È ÙÔÓ ·ÓÔÛÔ˚ÛÙÔ¯ËÌÈÎfi ¤ÏÂÁ¯Ô. ∏ ıÂÚ·›· Ù˘ ¯ÚfiÓÈ·˜ ÛÎÏËÚ˘ÓÙÈ΋˜ ÔÛÙÂÔÌ˘ÂÏ›Ùȉ·˜ Ù‡Ô˘ Garré ÔÊ›ÏÂÈ Ó· ÂÍÂÙ¿˙ÂÙ·È Û οı ÂÚ›ÙˆÛË Ì ÎÏÈÓÈο Î·È ÂÚÁ·ÛÙËÚȷο ÎÚÈÙ‹ÚÈ·. ¶ÔÏÏÔ› Û˘ÁÁÚ·Ê›˜ ÚÔÙ›ÓÔ˘Ó ÙËÓ ·ÓÙÈÌÈÎÚԂȷ΋ ·ÁˆÁ‹ ÁÈ· 4-6 ‚‰ÔÌ¿‰Â˜, ·Ó Î·È ‰ÂÓ ˘¿Ú¯Ô˘Ó Û·Ê›˜ ÂӉ›ÍÂȘ ‚ÂÏÙ›ˆÛ˘ Ù˘ ÎÏÈÓÈ΋˜ Î·È ·ÎÙÈÓÔÏÔÁÈ΋˜ ÂÈÎfiÓ·˜ Ì ÌfiÓ· Ù· ·ÓÙÈ‚ÈÔÙÈο (4,5). ÕÏÏÔÈ ÚÔÙÈÌÔ‡Ó ÙË ¯ÂÈÚÔ˘ÚÁÈ΋ ·ÓÙÈÌÂÙÒÈÛË, ÚÔÙ›ÓÔÓÙ·˜ ›Ù ÙÚ˘·ÓÈÛÌÔ‡˜ ÙÔ˘ ÛÎÏËÚ˘ÓÙÈÎÔ‡ ÊÏÔÈÔ‡ Û ‰È¿ÊÔÚ· ÛËÌ›· ›Ù (fiˆ˜ ÛÙË ‰È΋ Ì·˜ ÂÚ›ÙˆÛË) ÙË ‰È¿ÓÔÈÍË ·Ú·ı‡ÚÔ˘, ÙËÓ ÚÔÛ¤Ï·ÛË ÙÔ˘ ÔÛÙÈÎÔ‡ Ì˘ÂÏÔ‡ Î·È ÙÔÓ ÂÈÌÂÏ‹ ηı·ÚÈÛÌfi ·fi Ù· ÊÏÂÁÌÔÓÒ‰Ë ÛÙÔȯ›·, Ì·˙› Ì ÙËÓ ·fiÍÂÛË Ù˘ ‰ËÌÈÔ˘ÚÁËı›۷˜ ÎÔÈÏfiÙËÙ·˜ (4-6). ¶ÚfiÛÊ·Ù· ˘ÔÛÙËÚ›˙ÂÙ·È fiÙÈ Ë ÓfiÛÔ˜ ÙÔ˘ Garré ¤¯ÂÈ ÙÔ ›‰ÈÔ ·ıÔÁÂÓÂÙÈÎfi ˘fiÛÙڈ̷ Ì ÙË ¯ÚfiÓÈ· ˘ÔÙÚÔÈ¿˙Ô˘Û· ÔÏ˘ÂÛÙȷ΋ ÔÛÙÂÔÌ˘ÂÏ›Ùȉ· (2). °È· ÙÔ ÏfiÁÔ ·˘Ùfi, ÚÔÙ›ÓÂÙ·È Ë Ì·ÎÚfi¯ÚÔÓË ·Ú·ÎÔÏÔ‡ıËÛË Ù˘ ÓfiÛÔ˘, ÌÂÙ¿ ÙËÓ ·Ú¯È΋ Ù˘ ÂÓÙfiÈÛË Î·È ·ÓÙÈÌÂÙÒÈÛË, ÁÈ· ÙËÓ ¤ÁηÈÚË ÂÈÛ‹Ì·ÓÛË ÔÔÈ·Û‰‹ÔÙ Ӥ·˜ ˘ÔÙÚÔ‹˜ Û ¿ÏÏË ı¤ÛË.

µÈ‚ÏÈÔÁÚ·Ê›· 1. Salenius P, Vankka E. The development of the tibiofemoral angle in children. J Bone Joint Surg Am 1975;57:259-261.

2. Segev E, Hayek S, Lokiec F, Ezra E, Issakov J, Wientroub S. Primary chronic sclerosing (Garré’s) osteomyelitis in children. J Pediatr Orthop B 2001;10:360-364.

3. Belli E, Matteini C, Andreano T. Sclerosing osteomyelitis of Garré periostitis ossificans. J Craniofac Surg 2002;13:765-768.

4. Pettas N, Apostolopoulos A, Fliger I, Antonis K, Samaras P, Leonidou O. Chronic sclerosing osteomyelitis Garré. Case report presentation and review of the literature. Acta Orthop Trauma Hell 2007;58:220-223.

5. Styczynãski J, Bilinãski P, Lasek W, Gajewska-Guryn A, Wysocki M, Balcar-Boronã A. Garré type periostitis ossificans: effective antibiotic therapy case report and literature review. Case Rep Clin Pract Rev 2002; 3:46-50.

6. Sharma H, Taylor GR. Chronic sclerosing osteomyelitis of Garré affecting fifth metatarsal bone of the foot. The Foot 2003;13:209-211.

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11-14 ™ÂÙÂÌ‚Ú›Ô˘ 2008

42nd Annual Meeting ESPN (European Society for Paediatric Nephrology) Contact: Pierre Cochat, President of the Congress Tel.: +33 (0)4 72.11.03.46 Fax: +33 (0)4 72.11.03.43 E-mail: contact@agence-mo.com (Congress Organizer: Agence M.O.) Website: http://agencemo.soluscience.fr/sites/6-ESPN

Lyon, France

20-23 ™ÂÙÂÌ‚Ú›Ô˘ 2008

47th European Society for Pediatric Endocrinology Meeting Contact: Pauline Bertrand, ESPE Secretariat, BioScientifica, Euro House, 22 Apex Court. Woodlands, Bristol, BS32 4JT, UK Tel.: 44-0-01-454-642-208 Fax: 44-0-1-454-642-222 Website: www.espe2008.org

Istanbul, Turkey

25-27 ™ÂÙÂÌ‚Ú›Ô˘ 2008

European Conference on Paediatric Anaesthesia ¶ÏËÚÔÊÔڛ˜: Aktina-City Congress ∆ËÏ.: 210-3232433 Fax: 210-3232338 E-mail: feapa2008@aktinacitycongress.com

•ÂÓÔ‰Ô¯Â›Ô “Hilton”, ∞ı‹Ó·

26-27 ™ÂÙÂÌ‚Ú›Ô˘ 2008

Nutrition and Metabolism in Children: The Ages of Childhood Obesity Contact: Simona Sangiorgio Tel.: 39-0-224-449-248 Fax: 39-0-224-449-299 E-mail: s.sangiorgio@doc-congress.com

Verona, Italy

26-28 ™ÂÙÂÌ‚Ú›Ô˘ 2008

3Ë ∂ÈÛÙËÌÔÓÈ΋ ™˘Ó¿ÓÙËÛË Ù˘ ∂ÏÏËÓÈ΋˜ ∞η‰ËÌ›·˜ ¶·È‰È·ÙÚÈ΋˜ ¶ÏËÚÔÊÔڛ˜: Firstevent ∂.¶.∂. ∆ËÏ.: 210-8228950 Fax: 210-8228901 E-mail: info@firstevent.gr Website: www.firstevent.gr

•ÂÓÔ‰Ô¯Â›Ô “Aldemar Olympian Village”, ™Î·Êȉȿ ∏Ï›·˜ ¢. ¶ÂÏÔfiÓÓËÛÔ˜

2-6 √ÎÙˆ‚Ú›Ô˘ 2008

40th Congress of the International Society of Paedriatic Oncology Contact: Conference Secretariat: SIOP 2008 Secretariat, c/o MCI Berlin Office, Ines Paschen, Markgrafenstrasse 56, 10117 Berlin Tel.: 49-30-204-590 Fax: 49-302-045-950 E-mail: siop2008@cpb.de Website: www.siop2008.de

Berlin, Germany

8-11 √ÎÙˆ‚Ú›Ô˘ 2008

5th World Congress of European Club for Paediatric Burns Contact: Wyrzykowski Dariusz Tel.: 00-48-601-685-379 Fax: 00-48-583-026-427 E-mail: pedsurg@amg.gda.pl Website: http://www.5ecpb.org/

Gdansk, Poland

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11-14 √ÎÙˆ‚Ú›Ô˘ 2008

2008 National Conference & Exhibition of the American Academy of Pediatrics Contact: PediaLink Customer Service Tel.: 866-843-2271 E-mail: csc@aap.org / kidsdocs@aap.org

Boston, MA, United States

23-26 √ÎÙˆ‚Ú›Ô˘ 2008

31st Congress of the Union of Middle-Eastern & Mediterranean Pediatric Societies Contact: Prof. Ahmed Sahloul Essoussi Tel.: +216.73.219494/221411 Fax: +216.73.224899 E-mail: sahloulessoussi@ms.tn

Tunis, Tunisia

24-28 √ÎÙˆ‚Ú›Ô˘ 2008

EAP 2008 - 2nd Congress of the European Academy of Paediatrics Contact: Daniela Morein-Bar Tel.: 41-229-080-488 Fax: 41-227-322-850 E-mail: paediatrics@kenes.com Website: www.kenes.com/paediatrics/index.asp

Nice, France

25-26 √ÎÙˆ‚Ú›Ô˘ 2008

1Ô ¶·ÓÂÏÏ‹ÓÈÔ π·ÙÚÈÎfi ™˘Ó¤‰ÚÈÔ ÁÈ· ÙËÓ ˘Á›· ÙÔ˘ ¶·È‰ÈÔ‡ Î·È ÙÔ˘ ∂Ê‹‚Ô˘ Àfi ÙËÓ ·ÈÁ›‰· Ù˘ π·ÙÚÈ΋˜ ∂Ù·ÈÚ›·˜ Î·È ÙÔ˘ π·ÙÚÈÎÔ‡ ™˘ÏÏfiÁÔ˘ ª·ÁÓËÛ›·˜ Î·È ÛÂ Û˘ÓÂÚÁ·Û›· Ì ÙÔ ¶·ÓÂÈÛÙ‹ÌÈÔ ∞ıËÓÒÓ Î·È £ÂÛÛ·Ï›·˜ √ÚÁ¿ÓˆÛË: ∂Ù·ÈÚ›· ºÚÔÓÙ›‰·˜ ÀÁ›·˜ Î·È ∂Î·›‰Â˘Û˘ (∂ºÀ∫∂) & ∂ÏÏËÓÈ΋ ∂Ù·ÈÚ›· ∫ÔÈÓˆÓÈ΋˜ ¶·È‰È·ÙÚÈ΋˜ Î·È ¶ÚÔ·ÁˆÁ‹˜ Ù˘ ÀÁ›·˜ (∂∂∫¶¶À) - ∂›ÛÔ‰Ô˜ ÂχıÂÚË ¶ÏËÚÔÊÔڛ˜: ∞Ó·ÛÙ·Û›· ∞Ó·ÛÙ·Û›Ô˘, ¶Úfi‰ÚÔ˜ ∂ºÀ∫∂ ∆ËÏ.: 6937676725 E-mail: anasgr@gmail.com

µfiÏÔ˜

17-19 ¡ÔÂÌ‚Ú›Ô˘ 2008

1st International Congress of UENPS (Union of European Neonatal and Perinatal Societies) Global Neonatology & Perinatology Contact: L. Zmuda Tel.: 39-0-680-693-320 Fax: 39-0-680-692-586 E-mail: uenps2008@emec-roma.com Website: www.uenps2008.eu/homepage.htm

Rome, Italy

15-16 ¢ÂÎÂÌ‚Ú›Ô˘ 2008

∂ÓÙ·ÙÈ΋ ∂Î·›‰Â˘ÛË: 11Ô˜ ∫‡ÎÏÔ˜ “¶·È‰ÔÂÓ‰ÔÎÚÈÓÔÏÔÁ›·” √ÚÁ¿ÓˆÛË: ∂ÏÏËÓÈ΋ ∂Ó‰ÔÎÚÈÓÔÏÔÁÈ΋ ∂Ù·ÈÚ›· & ¶·ÓÂÏÏ‹ÓÈ· ŒÓˆÛË ∂Ó‰ÔÎÚÈÓÔÏfiÁˆÓ ∆ËÏ.: 210-7774370 Fax: 210-7701552 E-mail: info@endo.gr Website: www.endo.gr

∞ı‹Ó·