BEST1—One Gene, Many Diseases

Retinal dystrophies associated with the gene BEST1, collectively known as bestrophinopathies, are phenotypically heterogeneous. Although Best vitelliform macular dystrophy (BVMD) is the most common bestrophinopathy, the distinct clinical conditions encompassed by the bestrophinopathies vary in features, including the mode of inheritance and degree of macular vs peripheral retinal involvement. In this issue of JAMA Ophthalmology, Shah et al¹ assess the diversity of bestrophinopathies identified in the patient population of a single academic center. In an evaluation of 36 patients from 25 families for whom genetic testing results revealed disease-causing BEST1 sequence variants, the authors identify 3 of the distinct clinical phenotypes previously associated with this gene: BVMD, autosomal recessive bestrophinopathy (ARB), and adult-onset vitelliform macular dystrophy. Their cohort does not include individuals with autosomal dominant vitreoretinochoroidopathy or retinitis pigmentosa (RP). Indeed, the authors revisited a previously published family with a diagnosis of BEST1-associated autosomal recessive RP² and revised the clinical diagnosis to ARB. The identification of 2 patients with BEST1-associated adult-onset vitelliform macular dystrophy in this cohort is a reminder of the multiple pathways, both genetic and presumably multifactorial, that can culminate in this clinical phenotype.³