Clinical and Genetic Findings of Autosomal Recessive Bestrophinopathy (ARB)

Mutations in BEST1 cause several phenotypes including autosomal dominant (AD) Best vitelliform macular dystrophy type 2 (BVMD), AD vitreo-retino-choroidopathy (ADVIRC), and retinitis pigmentosa-50 (RP50). A rare subtype of Bestrophinopathy exists with biallelic mutations in BEST1. Its frequency is estimated to be 1/1,000,000 individuals. Here we report 6 families and searched for a genotype-phenotype correlation. All patients were referred due to reduced best-corrected visual acuity (BCVA), ranging from 0.1/10 to 3/10. They all showed vitelliform lesions located at the macula, sometimes extending into the midperiphery, along the vessels and the optic disc. Onset of the disease varied from the age of 3 to 25 years. Electrooculogram (EOG) revealed reduction in the EOG light rise in all patients. Molecular analysis revealed previously reported mutations p.(E35K);(E35K), p.(L31M);(L31M), p.(R141H);(A195V), p.(R202W);(R202W), and p.(Q220*);(Q220*) in five families. One family showed a novel mutation: p.(E167G);(E167G). All mutations were heterozygous in the parents. In one family, heterozygous children showed various reductions in the EOG light rise and autofluorescent deposits. Autosomal recessive Bestrophinopathy (ARB), although rare, can be recognized by its phenotype and should be validated by molecular analysis. Genotype-phenotype correlations are difficult to establish and will require the analysis of additional cases.