P ROS P ECTUS | V OL 46 | ISSUE 3 | 2021
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Choroideremia – Choroider-What? By: Bryan Wolynski OD, FAAO
Choroideremia (CHM) is an X-Linked disorder which affects 1 in 50,000 males in the U.S. and is a rare part of a group of disorders known as Inherited Retinal Dystrophies (IRD). This genetic disease causes initial nyctalopia, followed by peripheral field loss, with eventual visual acuity loss and finally central field loss. CHM is caused by a mutation in the CHM gene which makes the protein Rab Escort Protein 1 (REP-1) which is needed for intracellular trafficking and causes a slow degeneration of the photoreceptors, retinal pigment epithelium and the choroid which are visible on physical and imaging examination. Other IRD’s include, Stargardt disease, Cone-Rod Dystrophy, Lebers Congenital Amourosis, Gyrate Atrophy and the most common IRD; Retinitis Pigmentosa (RP). So, if CHM is rare, why should we be talking about it? Well, since the approval of Luxturna (voretigene neparvovec-rzyl) from Spark Therapeutics in 2017 and other potential ongoing trials and studies for the treatment of IRD’s; these dystrophies are now actionable and through gene therapy and no longer just tell someone there is nothing we can do medically. So why bring up Choroideremia in particular? An internal non-published study by the Choroideremia Research Foundation (CRF) found that ~70% of most of its members were initially diagnosed with RP. In fact, many papers have been reported on this misdiagnosis (1,2,3,4). A paper by Dr. Ian MacDonald reports that 6% of patients with diagnosis of RP related disorders have CHM (5). CHM and RP have similar symptoms and can be mistaken in diagnosis if not investigated carefully. Signs do vary, but there can be different phenotypes of expression where CHM early on, may seem similar to RP. The importance now is that there are emerging treatments and trials and as these trials continue it is important for our patients with an IRD be aware and get genetically tested to be sure of their diagnosis to consider and be part of a genetic registry and consider future treatments. RP can be caused by multiple gene mutations (such as RPE65, RPGR, SNRNP200 & CRB1) while CHM is only affecting the
REP-1; a misdiagnosis can affect outcomes and considerations for the patient. Of course we should still provide vision rehabilitation services and counseling, but now more than ever we should send our patients for genetic testing to confirm a diagnosis, especially if you note an atypical case of RP. You may in fact be seeing someone with CHM and not know it. As gene therapy advances having the right diagnosis matters. See below for similarities and differences of the signs and symptoms of CHM and RP. Remember to recommend genetic testing for all your IRD patients if they have not done so.
If anyone has a patient, they believe has CHM or diagnosed with CHM; you can refer them to the Choroideremia Research Foundation for further information on trials and genetic testing.
Choroideremia Research Foundation 23 E. Brundreth St., Springfield, Massachusetts 01109 800-210-0233 | info@curechm.org (1) P idro A, Ratkovic M, Pjano MA, Biscevic A. A Case Study of Choroideremia and Choroideremia Carrier. Med Arch. 2019 Feb;73(1):6162. (2) N anda A, Salvetti AP, Martinez-Fernandez de la Camara C, MacLaren RE. Misdiagnosis of X-linked retinitis pigmentosa in a choroideremia patient with heavily pigmented fundi. Ophthalmic Genet. 2018 Jun;39(3):380383. doi: 10.1080/13816810.2018.1430242. Epub 2018 Jan 29. (3) G uo H, Li J, Gao F, Li J, Wu X, Liu Q. Whole-exome sequencing reveals a novel CHM gene mutation in a family with choroideremia initially diagnosed as retinitis pigmentosa. BMC Ophthalmol. 2015 Jul 28;15:85. (4) Li S, Guan L, Fang S, Jiang H, Xiao X, Yang J, Wang P, Yin Y, Guo X, Wang J, Zhang J, Zhang Q. Exome sequencing reveals CHM mutations in six families with atypical choroideremia initially diagnosed as retinitis pigmentosa. Int J Mol Med. 2014 Aug;34(2):573-7.
Photos used with permission of the Choroideremia Research Foundation
(5) MacDonald IM, Hume S, Zhai Y, Xu M. Choroideremia. 2003 Feb 21 [updated 2021 Mar 4]. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Mirzaa G, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993–2021.
N YS OA. ORG | 5 18.449.7300. | INFO@NY SOA.ORG
