Choroideremia

Clinical characteristics: Choroideremia (CHM) is characterized by progressive chorioretinal degeneration in affected males and milder signs in heterozygous (carrier) females. Typically, symptoms in affected males evolve from night blindness to peripheral visual field loss, with central vision preserved until late in life. Although carrier females are generally asymptomatic, signs of chorioretinal degeneration can be reliably observed with fundus autofluorescence imaging, and – after age 25 years – with careful fundus examination.

Diagnosis/testing: The diagnosis of choroideremia is established in a male proband with suggestive findings and a hemizygous pathogenic variant in CHM identified by molecular genetic testing.

Management: Treatment of manifestations: Surgical correction of retinal detachment and cataract as needed; UV-blocking sunglasses for outdoors; appropriate dietary intake of fresh fruit, leafy green vegetables; antioxidant vitamin supplement as needed; regular intake of dietary omega-3 very-long-chain fatty acids, including docosahexaenoic acid; low vision services as needed; counseling as needed to help cope with depression, loss of independence, fitness for driving, and anxiety over employment issues.

Surveillance: Periodic ophthalmologic examination, kinetic visual field examination, and spectral domain optical coherence tomography (SD-OCT), especially when central vision is affected and cystoid macular edema is suspected.

Agents/circumstances to avoid: UV exposure from sunlight reflected from water and snow; smoking (a major risk factor for macular degeneration).

Genetic counseling: CHM is inherited in an X-linked manner. Affected males transmit the pathogenic variant to all of their daughters and none of their sons. Heterozygous females have a 50% chance of transmitting the variant in each pregnancy: males who inherit the pathogenic variant will be affected; females who inherit the pathogenic variant will be carriers and will usually not be symptomatic. Once the CHM pathogenic variant has been identified in an affected family member, carrier testing for at-risk female relatives, prenatal testing for a pregnancy at increased risk, and preimplantation genetic testing for choroideremia are possible.