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.

Background Genetic testing of patients with inherited kidney diseases has emerged as a tool of clinical utility by improving the patients’ diagnosis, prognosis, surveillance and therapy. Methods The present study applied a Next Generation Sequencing (NGS)-based panel, named NephroPlex, testing 115 genes causing renal diseases, to 119 individuals, including 107 probands and 12 relatives. Thirty-five (poly)cystic and 72 non (poly)cystic individuals were enrolled. The latter subgroup of patients included Bardet-Biedl syndrome (BBS) patients, as major components. Results Disease-causing mutations were identified in 51.5 and 40% of polycystic and non-polycystic individuals, respectively. Autosomal dominant polycystic kidney disease (ADPKD) patients with truncating PKD1 variants showed a trend towards a greater slope of the age-estimated glomerular filtration rate (eGFR) regression line than patients with (i) missense variants, (ii) any PKD2 mutations and (iii) no detected mutations, according to previous findings. The analysis of BBS individuals showed a similar frequency of BBS4,9,10 and 12 mutations. Of note, all BBS4-mutated patients harbored the novel c.332+1G>GTT variant, which was absent in public databases, however, in our internal database, an additional heterozygote carrier was found. All BBS4-mutated individuals originated from the same geographical area encompassing the coastal provinces of Naples. Discussion In conclusion, these findings indicate the potential for a genetic panel to provide useful information at both clinical and epidemiological levels. Graphic abstract