Ocular phenotypes of three genetic variants of Bardet-Biedl syndrome

Bardet-Biedl syndrome is a genetically heterogeneous multisystem disorder that causes severe visual impairment. Retinitis pigmentosa (RP), hypogonadism, digit and renal anomalies, obesity, and a variable degree of mental retardation characterize the disorder. Eight different loci have been identified on 2q31(BBS5), 3p13 (BBS3), 4q27 (BBS7), 11q13 (BBS1), 14q32 (BBS8), 15q22.3 (BBS4), 16q21 (BBS2), and 20p12 (BBS6). The ocular manifestations of Bardet-Biedl syndrome include an early and severe rod-cone dystrophy causing legal blindness in the second decade. Features of systemic phenotypic variability were proposed to distinguish patients mapped to either the BBS2, BBS3, or BBS4 loci but no phenotype-genotype correlation has been established for the ocular phenotype. We studied the three original families used for the identification of BBS2, BBS3, and BBS4 loci to define the ocular phenotypes of patients (n = 34) and obligate carriers (n = 32) using clinical examination and electroretinography (ERG). RP was severe and early in all cases. Myopia was associated with BBS3 and BBS4, but not BBS2. One patient with Bardet-Biedl syndrome also had iris and chorioretinal colobomata, features suggestive of Biemond syndrome.