Frequency, genotype, and clinical spectrum of best vitelliform macular dystrophy: Data from a national center in Denmark

• PURPOSE: To estimate the prevalence, genotype, and clinical spectrum of Best vitelliform macular dystrophy (Best disease). • DESIGN: Retrospective epidemiologic and clinical and molecular genetic observational study. • METHODS: SETTING: National referral center. PARTICIPANTS: Forty-five individuals diagnosed with Best disease. OBSERVATION PROCEDURES: Retrospective review of patients diagnosed according to clinical findings and sequencing of BEST1. Patients with recently established molecular genetic diagnosis were followed up including multifocal electroretinography (mfERG), spectral-domain optical coherence tomography (SD-OCT), and fundus autofluorescence (FAF) imaging. MAIN OUTCOME MEASURES: BEST1 mutations, SD-OCT and FAF findings, mfERG amplitudes, prevalence estimate of Best disease. • RESULTS: BEST1 mutations described previously in Danish patients with Best disease are reviewed. In addition, we identified a further 8 families and 1 sporadic case, in whom 6 BEST1 missense mutations were found, 4 of which are novel. The mutation c.904G>T (p.Asp302Asn) was identified in members of 4 unrelated families. Structural alterations ranged from precipitatelike alterations at the level of the photoreceptor outer segments (OS) to choroidal neovascularization. The extent of the former correlated with the reduction of retinal function. A prevalence estimate of Best disease in Denmark based on the number of diagnosed cases was 1.5 per 100 000 individuals. • CONCLUSIONS: Our data expand the mutation spectrum of BEST1 in patients with Best disease. Alterations of the OS overlying lesions with subretinal fluid are similar to those seen in central serous retinopathy and may indicate impaired turnover of OS. Our frequency estimate confirms that Best disease is one of the most common causes of early macular degeneration.