Bardet-Biedl Syndrome: Current Perspectives and Clinical Outlook

Abstract

The Bardet Biedl syndrome (BBS) is a rare inherited disorder considered a model of non-motile ciliopathy. It is in fact caused by mutations of genes encoding for proteins mainly localized to the base of the cilium. Clinical features of BBS patients are widely shared with patients suffering from other ciliopathies, especially autosomal recessive syndromic disorders; moreover, mutations in cilia-related genes can cause different clinical ciliopathy entities. Besides the best-known clinical features, as retinal degeneration, learning disabilities, polydactyly, obesity and renal defects, several additional clinical signs have been reported in BBS, expanding our understanding of the complexity of its clinical spectrum. The present review aims to describe the current knowledge of BBS i) pathophysiology, ii) clinical manifestations, highlighting both the most common and the less described features, iii) current and future perspective for treatment.

Bardet–Biedl syndrome: Delayed diagnosis in a 14‐year‐old child with end‐stage renal disease

“…As BBS has no definitive treatment, a supportive and symptomatic approach is needed while treating such patients 9 . These include training blind patients, rehabilitating intellectually disabled patients, hearing aids, speech therapy, exercise for weight management, and surgery for polydactyly 9 . Some studies suggest adopting a low‐protein & low‐calorie diet may help in both obesity control and halting the progression of renal impairment 16 .…”

“…It is an autosomal recessive genetic disorder. Till now, 26 genes have been identified (BBS1 to BBS22, NPHP1, CEP19, SCAPER, and SCLT1), which contribute to the development of this syndrome 9 . Bardet–Biedl Syndrome is classified as a non‐motile ciliopathy.…”

“…As BBS has no definitive treatment, a supportive and symptomatic approach is needed while treating such patients 9 . These include training blind patients, rehabilitating intellectually disabled patients, hearing aids, speech therapy, exercise for weight management, and surgery for polydactyly 9 .…”

The emerging functions of intraflagellar transport 52 in ciliary transport and ciliopathies

“…46 Individuals with BBS often report obesity, vision problems, renal anomalies and cognitive impairments. 46 The underlying genetic (BBS1, BBS2, BBS4, BBS5, BBS7, BBS10, BBS12, IFT27, IFT74, IFT172, CFAP418, CEP290, TMEM67, CCDC28B, ARL6, MKS1, MKKS, LZTFL1, TRIM32, SDCCAG8, PTHB1, TTC8, BBIP1 and WDPCP) mutations disrupt ciliary function, thereby impacting the body's ability to regulate appetite, metabolism, and sensory perception. 47 In addition to ADPKD and BBS, there are various other ciliopathies, each with its own set of clinical manifestations and genetic mutations.…”

“…One of the most extensively studied ciliopathies is autosomal dominant polycystic kidney disease (ADPKD), in which mutations of PKD1 or PKD2 result in the formation of fluid‐filled cysts in renal tubular cells, leading to kidney enlargement and failure 45 . Bardet‐Biedl syndrome (BBS) is another notable ciliopathy that manifests a wide range of clinical features in multiple organ systems 46 . Individuals with BBS often report obesity, vision problems, renal anomalies and cognitive impairments 46 .…”