Retinal Disease Expression in Bardet–Biedl Syndrome 1 (BBS1) Is a Spectrum From Maculopathy to Retina–Wide Degeneration

Abstract

Purpose: : To define the retinal phenotype in patients with the Bardet–Biedl syndrome and mutations in the BBS1 gene.

Methods: : Nine patients (age range, 16–48 years), representing 7 pedigrees, with BBS1 gene mutations were studied clinically and with kinetic perimetry, rod and cone perimetry, electroretinography and optical coherence tomography.

Results: : Of the 9 patients, 7 were M390R homozygotes while 2 patients were compound heterozygotes with one allele also being M390R. A spectrum of retinal disease expression was present. Mildest disease was a maculopathy with little or no peripheral retinal dysfunction. Maculopathy could present as a pigmentary disturbance, a foveal cystic lesion and/or foveal thinning. Moderate disease showed retina–wide rod>cone dysfunction. More severe disease expression had different patterns: either loss of central function but retained abnormal peripheral function, or a retained small central island of function only. Both patterns of field loss had rod>cone dysfunction. Moderate and severe disease showed loss of photoreceptor layer thickness across wide expanses of retina. Severity could differ in members of the same family and was independent of age.

Conclusions: : The wide spectrum of retinal disease severity in BBS1 indicates that the cardinal feature of retinal degeneration can show variability in degree. A macular phenotype associated with cardinal systemic features of the Bardet–Biedl syndrome should raise clinical suspicion of a BBS1 mutation.

Keywords: retinal degenerations: hereditary • degenerations/dystrophies