Genetic and clinical heterogeneity in LCA patients. The end of uniformity

Background: Leber congenital amaurosis (LCA) usually describes patients with severely reduced vision due to a retinal dystrophy in early childhood.

Methods: In 135 families in a case series with severely reduced vision due to a retinal dystrophy in early childhood a complete ophthalmologic examination was extended by two-color threshold perimetry, fundus autofluorescence (FAF), und optical coherence tomography (OCT). Mutation screening included AIPL1, CRB1, CRX, GUCY2D, LRAT, RPE65, RPGRIP, and TULP1.

Results: GUCY2D mutations caused the most severe phenotype with severely reduced vision from birth but unremarkable fundus appearance. RPE65 mutations were correlated with an obvious lack of FAF. CRB1 mutations showed a significantly thickened retina on OCT. CRX mutations were associated with a progressive form of cone-rod dystrophy.

Conclusions: A genotype-phenotype correlation for selected genes allows an optimized strategy for the molecular genetic work-up.