Gráficos de Crecimiento y Desarrollo disponibles para diferentes entidades clínicas. Utilidad y Uso Dr.Juan Pablo Llano L Endocrinólogo Pediatra y de la Adolescencia Junio de 2013
Caso Un paciente es remitido por talla baja por el medico general y asiste con la curva de crecimiento. Tiene diagnostico de trisomia 21 y recibe levotiroxina desde los 20 dias de vida.
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B-En niños con Síndrome de Down se deben usar los percentiles inferiores de las curvas de referencia C-Se debe evaluar el peso y talla en curvas especificas D-Debe ser remitido a un endocrinólogo pediatra para determinar si esta bajo o no.
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AC, Pueschel SM, et al. Growth charts for children with Down syndrome: 1 month to 18 years of age. Pediatrics. 1988;81:102–110.
Caso Un paciente es remitido por talla baja por el medico general y asiste con la curva de crecimiento. Tiene diagnostico de trisomia 21 y recibe levotiroxina desde los 20 dias de vida. Usted evalúa la curva de crecimiento y considera que A-El niño tiene una talla baja patológica B-En niños con Síndrome de Down se deben usar los percentiles inferiores de las curvas de referencia C-Se debe evaluar el peso y talla en curvas especificas D-Debe ser remitido a un endocrinólogo pediatra para determinar si esta bajo o no.
• Perform thyroid screening tests annually (3%–5% risk of hypothyroidism). • If appropriate, discuss skin problems: very dry skin and other skin problems are particularly common in patients with Down syndrome. • Discuss symptoms related to obstructive sleep apnea, including snoring, restless sleep, and sleep position. Refer to a specialist as indicated.20 Anticipatory Guidance
• Review the child’s development and appropriateness of school placement and developmental intervention.
• Discuss soc ships, incl guardianshi • Discuss the skills, self-h sense of res • Discuss psy sexual deve agement, fe • Discuss the bescent fem Down synd she were to that althoug
AMERIC
Entidades con alteración estatural – 100 años de descubrimientos 1866
1882
1878
1938
1896
1963
1953 1966
Patologías a Tratar • • • • • • •
Acondroplasia. Hipocondroplasia. Pseudo-acondroplasia. Síndrome de Down. Síndrome de Laron. Síndrome de Turner. Síndrome de Noonan. Síndrome de Marfán.
Entidades con alteración estatural – 100 años de descubrimientos 1866
Jhon Langdon Down-1866
Síndrome de Down • Alteración cromosómica mas frecuente. • Características clínicas: facies particular, orejas pequeñas, lengua grande, hipotonía, cardiopatías. • Alteración gonadal. • Talla final.
Pediatrics 2001 (107) 442
Comparaci贸n de talla Varones Percentil 50 (cm)
Mujeres Percentil 50 (cm)
Poblaci贸n general
176
163
S铆ndrome de Down
153 (-23)
145 (-18)
Entidades con alteración estatural – 100 años de descubrimientos 1866
1878
Jules Parrott 1878
Acondroplasia • Herencia. Incidencia. • Genética: 4p16.3. • Clínica: enanismo micromélico. Modificaciones craniofaciales. Hipotonía. Compromiso neuro. Talla final • Signos radiológicos.
Comparaci贸n de talla Varones Percentil 50 (cm)
Mujeres Percentil 50 (cm)
Poblaci贸n general
176
163
S铆ndrome de Down
153 (-23)
145 (-18)
Acondroplasia
131 (-45)
125 (-38)
Entidades con alteración estatural – 100 años de descubrimientos 1866
1882
1878
Friedrich Daniel von Recklinghausen 1882
Neurofibromatosis Enf. Von Recklinghausen Autosomica Dominante 1/3000 individuos Gen responsable en 17q11.2 Codifica DNA genomico de 350 Kb Ă ďƒ Neurofibromina
Criterios NIH (julio 1987) 2/7
Generalidades Alteraciones endocrinas en 1-3% pacientes. Ni単os pubertad precoz (3% vs 0.06%) Pubertad retardada Talla baja 13-24% Talla alta (tumores GH)
Adultos feocromocitoma Talla baja 40%
13%
Szudeck J, J Med Genet.2000,37:3933
Szudeck J, J Med Genet.2000,37:3933
Comparaci贸n de talla Varones Percentil 50 (cm)
Mujeres Percentil 50 (cm)
Poblaci贸n general
176
163
S铆ndrome de Down
153 (-23)
145 (-18)
Acondroplasia
131 (-45)
125 (-38)
NF1
170 (-6)
158 (-5)
Entidades con alteración estatural – 100 años de descubrimientos 1866
1882
1878
1896
Antoine Marfan 1896
Síndrome de Marfán • Autosómico dominante. Cromosoma 15 • Incidencia 1:100.000. • Clínicamente: alterac. músculoesqueléticas. Anomalías oculares y cardiovasculares
Pyertiz et al 1983
Comparaci贸n de talla Varones Percentil 50 (cm)
Mujeres Percentil 50 (cm)
Poblaci贸n general
176
163
S铆ndrome de Down
153 (-23)
145 (-18)
Acondroplasia
131 (-45)
125 (-38)
NF1
170 (-6)
158 (-5)
Marfan
188 (+12)
178 (+15)
Entidades con alteración estatural – 100 años de descubrimientos 1866
1882
1878
1938
1896
Henry Turner 1938
Síndrome de Turner • Ausencia total o parcial de un Cromosoma X • Incidencia. • Manifestaciones clínicas. • Tratamiento. • Factores que influencian la talla final.
Arch Dis Child 1985 (60) 932 1986
Comparaci贸n de talla Varones Percentil 50 (cm)
Mujeres Percentil 50 (cm)
Poblaci贸n general
176
163
S铆ndrome de Down
153 (-23)
145 (-18)
Acondroplasia
131 (-45)
125 (-38)
NF1
170 (-6)
158 (-5)
Marfan
188 (+12)
178 (+15)
Turner
143 (-20)
Entidades con alteración estatural – 100 años de descubrimientos 1866
1882
1878
1938
1896
1953
Sindrome Rusell Silver Henry Silver 1953 Alexander Rusell 1954
Figure 79 Height percentiles for Russ years. Source: From Wollman HA et al. Eu Springer Science and Business Media.
Figure 80 Height percentiles for Russell–Silver syndrome males from 0 to 20 years. Source: From Wollman HA et al. Eur J Pediatr 1995; 154:958; courtesy of Springer Science and Business Media.
Comparaci贸n de talla Varones Percentil 50 (cm)
Mujeres Percentil 50 (cm)
Poblaci贸n general
176
163
S铆ndrome de Down
153 (-23)
145 (-18)
Acondroplasia
131 (-45)
125 (-38)
NF1
170 (-6)
158 (-5)
Marfan
188 (+12)
178 (+15)
Turner Rusell Silver
143 (-20) 151.5 (-24.5)
139.5 (23.5)
Entidades con alteración estatural – 100 años de descubrimientos 1866
1882
1878
1938
1896
1963
1953
Jacqueline Noonan 1963
Jacqueline Noonan 1963
Síndrome de Noonan • Autosómico dominante a expresión variable • RASopatia • Clínica similar a la del ST, pero: • RM, mejor talla final, pubertad espontánea y cardiomiopatia. • Fertilidad. • Tratamiento.
Clin Genet 1986 (30)150
Comparaci贸n de talla Varones Percentil 50 (cm)
Mujeres Percentil 50 (cm)
Poblaci贸n general
176
163
S铆ndrome de Down
153 (-23)
145 (-18)
Acondroplasia
131 (-45)
125 (-38)
NF1
170 (-6)
158 (-5)
Marfan
188 (+12)
178 (+15)
Turner
143 (-20)
Rusell Silver
151.5 (-24.5)
139.5 (23.5)
Noonan
160 (-16)
148 (-15)
Entidades con alteración estatural – 100 años de descubrimientos 1866
1882
1878
1938
1896
1963
1953
1966
The clinical history, appearance, and laboratory findings resembled those found in children with isolated growth hormone deficiency (IGHD) (Laron 1983) (Fig. 1.2). When radioimmunoassays for GH became available (Glick et al. 1963; Laron and Mannheimer 1966), we were astonished to find that their serum GH levels were very high. A short while thereafter, we were able to assemble 22 patients, all products of consanguineous Jewish families originating from mid-Eastern countries or North Africa (Laron et al. 1968) (Fig. 1.3). The striking finding was their typical appearance and the great resemblance between patients (Fig. 1.4).
Zvi Laron 1966
Z. Laron Schneider Children’s Medical Center of Israel, Endocrine Research Unit, Kaplan Street 14, 49202 Petah Tikva, Israel e-mail: laronz@clalit.org.il
Fig. 1.1 Two of the 3 first patients with Laron syndrome (LS) referred to us in 1958. The girl (SR), 1.5 years old; and the boy (SSi), 3.5 years old. Note obesity, sparse hair, and saddle nose. Reproduced with permission from Laron (2004)
Z. Laron and J. Kopchick (eds.), Laron Syndrome - From Man to Mouse, DOI: 10.1007/978-3-642-11183-9_1, Š Springer-Verlag Berlin Heidelberg 2011
3
Síndrome de Laron • Alteración de RGH. p13.1 • Manifestaciones clínicas. • Exámenes de laboratorio. • Tratamiento.
known commercial routes (spice and silk) or emigration routes (Jews from Spain and Portugal took refuge in South-America during the Inquisition; or Arabs and Jews from the Middle-East emigrated to South-America from nineteenth to twentieth century (Rosenbloom et al. 1990)), make one realize that the GH-R defects may have traveled during centuries between continents and between countries. Indeed, travel and migration are not new phenomena but go back to Biblical times and even earlier. So it seems that the origin of many diseases including Laron syndrome is ancient. The existence of dwarfs with the appearance of Laron syndrome in the middle ages is plastically exemplified in the painting by Mantegna from 1454 in the Palace of Mantova (Battin 1996) (Fig 5.19), but the history of this syndrome seems to go further back. Comparison between the roentgenological findings of the skeleton of our large cohort of patients with Laron syndrome (Chap. 20) and the skeletal remains of “Homo floresiensis” in Indonesia (Brown et al. 2004), thought to be 18–20,000 years old and characterized by dwarfism (body height 106 cm) and a small head (Morwood et al. 2005), revealed many resemblances between that skeleton and Laron syndrome (Hershkovitz et al. 2007). As Laron syndrome occurs more often in consanguineous families (Shevah et al. 2006) and isolates such as
Fig. 5.19 The enlarged picture of a dwarfed lady by Mantegna 1454. Note the typical facial features
in the Bahamas (Baumbach et al. 1997) o (Rosenbloom et al. 1990), and having been d patients from several countries in South including Pakistan (Rosenfeld et al. 1994), In et al. 1993), Cambodia (Vesterhus 1997) (Walker et al. 1998), and Malaysia (Harun communication), we put forward the hypo “homo floresiensis” does not belong to a “ne but belongs to a locally inbred population of “ ens” in whom a GH-receptor mutation has o old times (Hershkovitz et al. 2007) and has b cally transmitted in that isolate for many g This so far unidentified mutation(s) harborin the “founder gene” for Laron syndrome has with time along the “spice and silk roads” from Asia to the Middle East and the Mediterran and from there to South and Central America On its way, it has encountered epigenetic cha ing to different “de novo” mutations. Support for our hypothesis are the follow findings: Investigating our Laron syndrom
6.1.12 Photography Medical photography was performed at the Photography and Graphic Institute, Beilinson Hospital.
The long-term follow-up from infancy into adult age of 24 patients with Laron syndrome (10 boys and 14 girls) and their frequent measurements by the same nurses enabled us to construct growth charts for this syndrome (Laron et al. 1993). Further experience showed that they fit all syndromes of true congenital GH/IGF-I
deficiency except ALS (acid labile subunit of IGFBP3) mutations (Laron and Silbergeld 2006).
6.2.1 Methods
Fig. 6.2 Laron syndrome-specific growth chart for height in girls from birth to 20 years (Laron et al. 1993)
The growth increments over periods of 1–3 years were calculated for each sex separately. These increments enabled us to plot the growth velocity curve. The height curves were constructed using the TannerGupta method (Tanner 1951) as follows: the mean height was calculated for boys at the age of 10 years and for
girls at the age of 8 years. Fro calculated yearly growth incre tracted going backwards to bir the age of 20 years. Both the g curves were smoothed usin (Cleveland 1979). The final he the subjects grew less than 1 c Figures 6.2 and 6.3 repres growth charts as mean (Âą2 SD Laron syndrome (Laron et charts it is seen that the spre wider in boys than in girls. velocity slows and after th
Comparaci贸n de talla Varones Percentil 50 (cm)
Mujeres Percentil 50 (cm)
Poblaci贸n general
176
163
S铆ndrome de Down
153 (-23)
145 (-18)
Acondroplasia
131 (-45)
125 (-38)
NF1
170 (-6)
158 (-5)
Marfan
188 (+12)
178 (+15)
Turner
143 (-20)
Rusell Silver
151.5 (-24.5)
139.5 (23.5)
Noonan
160 (-16)
148 (-15)
Laron
125 (-51)
124 (-39)
Entidades con alteración estatural – 100 años de descubrimientos 1866
1882
1878
1938
1896
1963
1953
1966
70’S-2013
Hipocondroplasia • Herencia. • Clínicamente similar a la acondroplasia, con pocas manifestaciones faciales. • Radiología. • La talla final.
Comparaci贸n de talla Varones Percentil 50 (cm)
Mujeres Percentil 50 (cm)
Poblaci贸n general
176
163
S铆ndrome de Down
153 (-23)
145 (-18)
Acondroplasia
131 (-45)
125 (-38)
NF1
170 (-6)
158 (-5)
Marfan
188 (+12)
178 (+15)
Turner
143 (-20)
Rusell Silver
151.5 (-24.5)
139.5 (23.5)
Noonan
160 (-16)
148 (-15)
Laron
125 (-51)
124 (-39)
Hipocondroplasia
156 (-20)
144 (-19)
Pseudo - Acondroplasia • Retardo estatural en el 2º año, con problemas de la marcha. • Aspectos clínicos. • Transmisión AD. • Cromosoma 19 • Estudio radiológico. • Patogenia.
Am J Dis Chid 1983 (136)31601
Comparaci贸n de talla Varones Percentil 50 (cm)
Mujeres Percentil 50 (cm)
Poblaci贸n general
176
163
S铆ndrome de Down
153 (-23)
145 (-18)
Acondroplasia
131 (-45)
125 (-38)
NF1
170 (-6)
158 (-5)
Marfan
188 (+12)
178 (+15)
Turner
143 (-20)
Rusell Silver
151.5 (-24.5)
139.5 (23.5)
Noonan
160 (-16)
148 (-15)
Laron
125 (-51)
124 (-39)
Hipocondroplasia
156 (-20)
144 (-19)
Pseudohipocondroplasia
119 (-57)
118 (-45)
Gráficos de Crecimiento y Desarrollo disponibles para diferentes entidades clínicas. Utilidad y Uso Dr.Juan Pablo Llano L Endocrinólogo Pediatra y de la Adolescencia Junio de 2013
J Clin Endocrinol Metab 2006; 91:4235
GH GHR
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Gráficos de Crecimiento y Desarrollo disponibles para diferentes entidades clínicas. Utilidad y Uso Dr.Juan Pablo Llano L Endocrinólogo Pediatra y de la Adolescencia Junio de 2013