Choroideremia is characterized by extensive loss of all retinal layers in the eyes. This disorder usually begins during childhood with wasting (atrophy) of the pigmented retinal epithelium, retina, and choroid. The retina is the light sensitive, most internal layer, consisting of many nerve containing layers. A layer of single pigmented cells is the layer outside of the retina. The choroid is the next layer located between the retina and the “white” section of the eye (the sclera); this layer contains small blood vessel).
Degeneration of the blood vessels of the choroid is followed by damage to the retina, which usually leads to loss of peripheral vision that can progress to eventual blindness. Central vision is usually preserved until late in life. The symptoms of choroideremia may vary greatly between affected individuals. Female carriers usually have very mild symptoms with night blindness or sensitivity to glare occurring late in life.
Choroideremia can be caused by many different mutations in the CHM gene. The CHM gene encodes REP1 (RAB escort protein 1), a protein that takes part in targetomg vesicles (small sacs of substances) in and out of cells.
Choroideremia is an X linked recessive genetic condition. These disorders are caused by an abnormal gene on the X chromosome and manifest mostly in males. Females who have an altered gene on one of their X chromosomes are carriers for that disorder. Carrier females usually do not display symptoms, because females have two X chromosomes and only one carries the altered gene. Males have one X chromosome that is inherited from their mothers; if a male inherits an X chromosome that contains the altered gene, he will develop the disease.
Female carriers of an X linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.
If a male with an X linked disorder has a child, he will pass the altered gene to all of his daughters, who will be carriers. A male cannot pass an X linked gene to his sons because males always pass their Y chromosomes instead of their X chromosome to male offspring.
Choroideremia affects primarily males. Female carriers generally have few or no symptoms. However, a small number of females develop the disorder as a result of a genetic process that inactivates the normal gene and leaves only the dysfunctional gene active. In the Salla area of northern Finland, an unusually high number of people have been diagnosed with choroideremia; approximately one in forty persons.
A doctor will perform tests that examine the patient’s visual field suspected of having choroideremia and will look inside the eye for degeneration of the retina. Genetic testing is available for some genetic variants that cause choroideremia.
The symptoms of choroideremia can be treated but the disease itself cannot yet be cured. Organizations providing services to sight impaired people help patients and their families. Genetic counseling is recommended for families affected by this disorder.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/ct2/results?term=choroideremia&Search=Search.
All studies receiving U.S. government funding, and some supported by private industry, are posted on this government website.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Toll‑free: (800) 411‑1222
TTY: (866) 411‑1010
For more information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
Coussa RG, Traboulsi EI. Choroideremia: a review of general findings and pathogenesis. Ophthalm Genet 2012;33(2):57 65.
Mitra S, Cheng KW, Mills GB. Rab GTPases implicated in inherited and acquired disorders. Seminars Cell Develop Biol. 2011;22(1):57 68.
Pereira Leal JB, Hume AN, Seabra MC. Prenylation of Rab GTPases: molecular mechanisms and involvement in genetic disease. FEBS Lett 2001;498:197 200.
Coussa RG, Kim J, Traboulsi E. Choroideremia: effect of age on visual acutity in patients and female carriers. Ophthmal Genet 2012;33(2)66 73.
Köhnke M, Delon C, Hastie ML, Nguyen UTT, Wu Y W, Waldmann H, et al. Rab GTPase prenylation hierarchy and its potential role in choroideremia disease. PLoS One 2013;8(12):e81758.
Lazow MA, Hood DC, Ramachandran R, Burke TR, Wang Y-Z, Greenstein VC, et al. Transition zones between healthy and diseased retina in choroideremia (CHM) and Stargardt disease (STGD) as compared to retinitis pigmentosa (RP). Invest Ophthalmol Vis Sci 2011;52(13):9581-90.
MacDonald IM, Russell L, Chan C-C. Choroideremia: new findings from ocular pathology and review of recent literature. Surv Ophthalmol 2009;54(3):401 407.
MacLaren RE, Groppe M, Barnard AR, Cottriall CL, Tolmachova T, Seymour L, et al. Retinal gene therapy in patients with choroideremia: initial findings from a phase 1/2 clinical trial. Lancet 2014;383(9923):1129 37.
Roberts MF, Fishman GA, Roberts DK, Heckenlively JR, Weleber RG, Anderson RJ, et al. Retrospective, longitudinal, and cross sectional study of visual acuity impairment in choroideraemia. Br J Ophthalmol 2002;86(6):658 62.
Seabra, M. C., Brown, M. S., Goldstein, J. L. Retinal degeneration in choroideremia: deficiency of Rab geranylgeranyl transferase. Science 1993;259:377 381.
Tolmachova T, Anders R, Abrink M, Bugeon L, Dallman MJ, Ramalho JS et al. Independent degeneration of photoreceptors and retinal pigment epithelium in conditional knockout mouse models of choroideremia. J Clin Invest 2006;116:386–94.
MacDonald IM, Hume S, Chan S, et al. Choroideremia. 2003 Feb 21 [Updated 2015 Feb 26]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: http://www.ncbi.nlm.nih.gov/books/NBK1337/ Accessed September 22, 2015.
McKusick VA., ed. Online Mendelian Inheritance in Man (OMIM). Baltimore. MD: The Johns Hopkins University; Entry No: 303100; Last Update: 07/08/2014. Available at: http://omim.org/entry/303100 Accessed September 22, 2015.
Orphanet. Choroideremia. Last update: December 2011. Available at http://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=180 Accessed September 22, 2015.