RPE65-related disorders are conditions that impact the retina of the eye, leading to severe vision loss or blindness, usually in the first ten years of life. However, there’s a range of cases, from blindness at birth to progressive vision loss in adulthood.
The most severe form, called Leber congenital amaurosis type 2 (LCA2), results in blindness before the age of one. Infants with LCA2 are often born blind or lose their vision within a few months. They might show unusual behaviors like rubbing or poking their eyes. Some individuals with LCA2 may also have developmental delays or intellectual disabilities.
Retinitis pigmentosa type 20 (RP20) is a less aggressive form, usually starting in childhood. It’s one of many types of retinitis pigmentosa. Symptoms begin between 3 and 7 years of age, starting with night blindness and progressing to a general decline in vision. The speed of progression varies, with some experiencing severe vision loss early (between 5 and 12 years), while others develop it more slowly, not losing vision until adulthood.
There’s no cure for RPE65-related disorders, and the primary approach is supportive care. Glasses, low-vision aids, and supportive services for vision impairment may be helpful. Gene therapy trials for these disorders are ongoing, showing some improvement in vision under different light conditions, although more research is needed.
These conditions are caused by pathogenic (disease-causing) variants in the RPE65 gene and exhibits autosomal recessive inheritance. This means that both parents must be carriers to have a 25% chance to have a child with the condition. The risk of being a carrier is based on a person’s ancestry or ethnic background. For example, individuals of Sephardic Jewish descent have a 1 in 90 chance to be a carrier.
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Revised November 2023
