Autosomal recessive Bardet–Biedl syndrome: first-degree relatives have no predisposition to metabolic and renal disorders

Bardet-Biedl Syndrome (BBS) is an autosomal recessive, multisystem, genetically heterogeneous, ciliopathic condition caused by mutations in multiple genes. Here we sought to determine if inheritance of a single BBS mutation increased the risks of frequent disorders of this syndrome such as obesity, hypertension, and diabetes. Various metabolic and renal diseases in a cohort of 46 patients with BBS, prospectively followed for up to 28 years, were compared to recent assessments of these factors in 96 relatives with a heterozygote mutation (carriers) and 37 relatives without a contributing mutation (non-carriers). Ten mutations in 6 genes causing this syndrome were identified in 21 families from whom DNA was obtained. The body mass index or the incidences of hypertension, diabetes, or stage 3 chronic kidney diseases were found to be similar between carriers and non-carriers but were all significantly less than those of family members with BBS. Similarly, the median age of onset of hypertension or diagnosis of stage 3 kidney disease, or the diagnosis of diabetes by age 70 were all significantly lower in those with BBS than in gene carriers or non-carriers. While our study shows that metabolic and renal events occurred frequently and at an early age in BBS, the heterozygous inheritance of any of the 10 described BBS mutations did not predispose family members to obesity, diabetes, hypertension, or renal impairment.