Abstract
BackgroundBardet-Biedl syndrome (BBS) is a rare genetic disorder that features retinal degeneration, obesity, polydactyly, learning disabilities and renal abnormalities. The diagnosis is often missed at birth, the median age at diagnosis being 9 years. In the attempt to shed light on BBS and improve its diagnosis and treatment, we evaluated the genotype-phenotype relationship in patients with a molecular diagnosis of BBS.MethodsWe analyzed three common BBS genes, BBS1, BBS10 and BBS2, in 25 Italian patients fulfilling the clinical criteria of BBS. In 12 patients, we identified gene-specific biallelic variants and thus correlated genotype to the ophthalmic, renal and audio-vestibular phenotypes.ResultsAt least one sequence variant was found in 60% of patients. The most common mutated gene was BBS1 followed by BBS10. Of the 17 sequence variants we found, 11 have not previously been associated with BBS. In 12 patients, we identified biallelic pathogenic variants; they had retinitis pigmentosa with early onset of visual impairment. However, retinal dystrophy was less severe in patients with BBS1 than in those with BBS10 variants. Overall, we found a high prevalence of renal dysmorphism and dysfunction. Notably, patients with BBS10 variants had the most severe renal impairment, which resulted in a critical decline in renal function. All the patients who underwent audio-vestibular evaluation had dysfunction of the cochlear outer hair cells, thus confirming the presence of hearing defects.ConclusionBBS1, BBS2 and BBS10 are major causative genes in Italian BBS patients. BBS10 was associated with the worse outcome in terms of the renal, ocular and audiovestibular phenotypes. Cochlear dysfunction should be included among the hallmarks of BBS.
Highlights
Bardet-Biedl syndrome (BBS) is a rare genetic disorder that features retinal degeneration, obesity, polydactyly, learning disabilities and renal abnormalities
BBS10 was associated with the worse outcome in terms of the renal, ocular and audiovestibular phenotypes
In addition to retinitis pigmentosa (RP), the main features of our patients that were consistent with the clinical diagnosis of BBS were postaxial polydactyly (21/25 patients), obesity (15/25 patients), a history of obesity (2/ 25 patients), renal abnormalities (18/21 patients)
Summary
Bardet-Biedl syndrome (BBS) is a rare genetic disorder that features retinal degeneration, obesity, polydactyly, learning disabilities and renal abnormalities. Bardet-Biedl syndrome (BBS) is a systemic hereditary disorder characterized by the coexistence of rod-cone dystrophy, polydactyly, obesity, cognitive impairment, and renal dysfunction. Or syndactyly are generally the first signs recognized at birth, while visual defects, obesity and cognitive impairment develop during the first year of age [2]. Patients experience progressive night blindness, followed by photophobia and loss of central and color vision. At clinical level, they show marked reduction of electroretinogram (ERG) amplitude, which depends on a primary loss of rod photoreceptors followed by cone death [4]. Hearing loss is not considered a main feature of BBS, and has been reported in only two studies [7, 8]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
