Bardet‐Biedl syndrome: A focus on genetics, mechanisms and metabolic dysfunction

Abstract

Bardet‐Biedl syndrome (BBS) is a rare, monogenic, multisystem disorder characterized by retinal dystrophy, renal abnormalities, polydactyly, learning disabilities, as well as metabolic dysfunction, including obesity and an increased risk of type 2 diabetes. It is a primary ciliopathy, and causative mutations in more than 25 different genes have been described. Multiple cellular mechanisms contribute to the development of the metabolic phenotype associated with BBS, including hyperphagia as a consequence of altered hypothalamic appetite signalling as well as alterations in adipocyte biology promoting adipocyte proliferation and adipogenesis. Within this review, we describe in detail the metabolic phenotype associated with BBS and discuss the mechanisms that drive its evolution. In addition, we review current approaches to the metabolic management of patients with BBS, including the use of weight loss medications and bariatric surgery. Finally, we evaluate the potential of targeting hypothalamic appetite signalling to limit hyperphagia and induce clinically significant weight loss.

Phenotypic and genotypic analysis of 11 fetal cases with Bardet–Biedl syndrome

“…To date, more than 25 different genes have been reported to be associated with BBS. 2 In postnatal life, clinical diagnosis of BBS is based on the presence of at least four primary features or a combination of three primary plus two secondary features. 3 Owing to the phenotypic heterogeneity of BBS, and also the absence of functional features on fetal ultrasound, prenatal diagnosis is challenging.…”