Leber congenital amaurosis

Leber congenital amaurosis (LCA) is a group of inherited retinal dystrophies that represents one of the most severe forms of childhood-onset visual impairment. Also known as Leber's congenital amaurosis or congenital retinal blindness, LCA primarily affects the retina — the light-sensitive tissue at the back of the eye. It is the most common genetic cause of blindness in infants and children, typically presenting at birth or within the first few months of life. The condition is caused by pathogenic variants in at least 25 different genes (including RPE65, CEP290, GUCY2D, CRB1, AIPL1, and others), all of which play critical roles in retinal development or function, particularly in photoreceptor cells or the retinal pigment epithelium. Key clinical features include severe visual impairment or blindness from birth, nystagmus (involuntary rhythmic eye movements), sluggish or absent pupillary light reflexes, and a markedly reduced or non-recordable electroretinogram (ERG). Many affected children exhibit the oculodigital sign of Franceschetti, in which they habitually press, poke, or rub their eyes. Fundoscopic examination may initially appear normal but can progressively show retinal changes including pigmentary deposits, attenuated blood vessels, and optic disc pallor. Some genetic subtypes of LCA may be associated with additional systemic features such as intellectual disability, renal anomalies (particularly nephronophthisis in CEP290-related disease), or central nervous system involvement. The treatment landscape for LCA has been transformed by the approval of voretigene neparvovec (Luxturna), a gene therapy specifically designed for patients with biallelic RPE65 mutations. This was the first FDA-approved gene therapy for an inherited disease and has demonstrated meaningful and sustained improvements in functional vision. For other genetic subtypes, management remains largely supportive, including low-vision aids, orientation and mobility training, and educational support. Numerous clinical trials are underway investigating gene therapies, antisense oligonucleotides (particularly for CEP290-related LCA), and other molecular approaches for additional genetic forms of the disease.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

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