Retinal disease expression in Bardet-Biedl syndrome-1 (BBS1) is a spectrum from maculopathy to retina-wide degeneration

PURPOSE. To define the retinal phenotype in patients with the Bardet-Biedl syndrome and mutations in the BBS1 gene. METHODS. Ten patients (age range, 16 - 48 years), representing eight pedigrees, with BBS1 gene mutations were studied clinically and with kinetic perimetry, chromatic static perimetry, electroretinography (ERG), and optical coherence tomography. RESULTS. Of the 10 patients, 8 were M390R homozygotes and 2 were compound heterozygotes with one allele also M390R. A spectrum of retinal disease expression was present. The mildest disease was a subtle maculopathy with relatively limited peripheral retinal dysfunction. Moderate disease showed retina-wide rod > cone dysfunction, and often there was a negative ERG waveform. More severe disease expression had different patterns: either loss of central function but retained abnormal peripheral function or a retained small central island of impaired function only. Moderate and severe disease showed loss of retinal and photoreceptor layer thickness across wide expanses of retina. Severity differed in family members and was independent of age. In addition, severity was not explained by genotype at a recently reported BBS epistatic gene, MGC1203. CONCLUSIONS. The cardinal feature of retinal degeneration in BBS1 can show a wide spectrum of disease expression.