Leber congenital amaurosis

Leber congenital amaurosis (LCA) is a rare inherited eye disease that appears at birth or in the first few months of life. It affects about 1 in 40,000 newborns. LCA was first described by Theodor Leber in the 19th century. It should not be confused with Leber's hereditary optic neuropathy, which is a different disease also described by Theodor Leber. One form of LCA was successfully treated with gene therapy in 2008. LCA symptoms typically begin in the first few months of life, most commonly with involuntary twitching of the eye (nystagmus). Affected infants may show misaligned eyes when looking at something (strabismus), aversion to light (photophobia), and poke or rub at their eyes (Franceschetti’s oculodigital sign). Those with LCA invariably experience vision problems. Affected infants show decreased visual response to objects. Loss of visual acuity is severe, with affected individuals' vision ranging from 20/200 to 20/400. Around a third of those affected completely lose perception of light. At an eye exam, the pupils may not respond normally to light. Some affected individuals have cloudy eyes (cataracts), and irregularly shaped corneas (keratoconus). Retinal exams typically look normal, especially in the young, though retinal abnormalities can appear later in life. Aside from eye problems, children with LCA are typically healthy. LCA is a genetic disease, and can be caused by pathogenic variants in at least 28 different genes. Variants in three of these genes – IMPDH1, OTX2, and CRX – can cause LCA in an autosomal dominant manner, meaning inheriting a single copy of a pathogenic variant can result in disease. Variants in the remaining genes associated with LCA cause disease in an autosomal recessive manner, meaning one must inherit copies of the pathogenic variant from both parents to develop LCA.