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Choroideremia is characterized by a progressive atrophy of photoreceptors, retinal pigment epithelium (RPE) and choroid. Areas of RPE atrophy are present early in the mid-periphery and progress centrally. This is associated with loss of photoreceptors and the choriocapillaris.
Night blindness is the first symptom often with onset during childhood. A ring-like perimacular scotoma develops that progresses into the periphery during life with corresponding visual field loss (peripheral constriction). Symptoms and fundus changes are highly variable. Visual acuity is generally well maintained into later stages of the disease but some males are blind by age 30 years whereas others over the age of 50 are symptom-free. An increased prevalence of myopia has been noted.
Males with choroideremia (and some females) have progressive loss of the choriocapillaris eventually baring the sclera beneath. Female carriers can exhibit patchy areas of RPE atrophy in the periphery and these may enlarge. Female carries are typically not symptomatic, but there are reports of females being fully affected. Females may also have visual field changes and defective dark adaptation. OCT in young women shows dynamic changes and remodeling of the outer retina with time with focal retinal thickening, drusenlike deposits and disruptions in photoreceptor inner and outer segment junctions even in younger individuals. The phenotype is more severe in older females as well suggesting that the retinal degeneration is progressive in both sexes.
Electroretinography (ERG) initially shows a decreased dark-adapted response with intact light-adapted responses, indicating general dysfunction of rod photoreceptors. Cone dysfunction, however, develops with progression of the disease.
No general systemic manifestations are associated with choroideremia. This may be explained by systemic expression of REP2, Rab escort protein-2, compensating for the decreased level of REP1.
There are occasional reports of associated deafness and obesity in some families with choroideremia (303110) but it is uncertain if this represents a unique disorder.
Choroideremia is an X-linked recessive disorder affecting males and occasional female carriers. The disorder is caused by mutations in the CHM gene on the X chromosome (Xq21.2) which leads to absence or truncation of the protein Rab escort protein-1 (REP1) that is part of Rab geranylgeranyltransferase, an enzyme complex involved in intracellular vesicular transport. A few patients with chromosomal translocations involving the relevant region of the X chromosome have been reported.
There is presently no effective treatment for the disorder, but visual function can be improved with low vision aids.
Recent early trials using adeno-associated viral vectors containing DNA coding the REP1 protein have documented improved rod and cone function in 6 affected males.