EVER Past president lecture: lessons from the Fascinating World of Bestrophinopathies

Abstract

SummaryPurposeTo describe the genotypes and phenotypes in patients with bestrophinopathies.MethodsExamples of Best vitelliform macular dystrophy will be compared with the phenotype of patients with autosomal recessive bestrophinopathy and autosomal dominant vitreoretinochoroidopathy.ResultsPhenotypes of BVMD range from asymptomatic, normal fundi in heterozygous BEST1 mutation carriers, to classic macular egg yolk‐like lesions. Biallelic BEST1 mutations cause ARB, characterized by shallow retinal detachments in the posterior pole, with hyperautofluorescent deposits in the watershed zone and superonasal to the optic disc. In addition, there are small, inner retinal, cystoid changes. Rod‐cone dystrophy (RCD) develops later. Subacute angle closure glaucoma is frequent. ADVIRC patients show a 360° peripheral hyperpigmented band, peripapillary staphylomata, RCD and microcornea. Unique mutations in one BEST1 allele cause ADVIRC. Electro‐oculography is abnormal in all bestrophinopathies first.ConclusionsBestrophinopathies are a diverse group of conditions caused by either mono‐ or biallelic mutations in BEST1. Whereas ADVIRC is very different, BVMD and ARB show considerable overlap. This suggests that a threshold of bestrophin protein production, blurring the differences between dominant or recessive mechanisms of disease, may be the main determinant of the phenotype. Abnormal EOGs indicate primary RPE involvement.