New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey

TLDR

Bardet‑Biedl syndrome is an autosomal recessive disorder with rod‑cone dystrophy, polydactyly, obesity, intellectual disability, hypogonadism, and renal dysfunction, but variable expression makes diagnosis challenging. The study aimed to refine BBS diagnostic criteria by surveying 109 patients and families, proposing revisions and a unifying label to enable earlier diagnosis and highlight overlap with Laurence‑Moon syndrome. The authors conducted a population survey of 109 BBS patients and their families, the largest cohort examined to date. The survey revealed late diagnosis (average 9 years), early polydactyly (69 % at birth), delayed obesity and retinal degeneration, novel neurological, speech, behavioral, facial, and dental features, an overlap with Laurence‑Moon syndrome, higher renal malformations and renal cell carcinoma in heterozygous relatives, underscoring the need for earlier diagnosis and expanded clinical surveillance.

Abstract

Bardet-Biedl syndrome (BBS) is an autosomal recessive condition characterised by rod-cone dystrophy, postaxial polydactyly, central obesity, mental retardation, hypogonadism, and renal dysfunction. BBS expression varies both within and between families and diagnosis is often difficult. We sought to define the condition more clearly by studying 109 BBS patients and their families, the largest population surveyed to date. The average age at diagnosis was 9 years, which is late for such a debilitating condition, but the slow development of the clinical features of BBS probably accounts for this. Postaxial polydactyly had been present in 69% of patients at birth, but obesity had only begun to develop at around 2-3 years, and retinal degeneration had not become apparent until a mean age of 8.5 years. Our study identified some novel clinical features, including neurological, speech, and language deficits, behavioural traits, facial dysmorphism, and dental anomalies. In the light of these features we propose a revision of the diagnostic criteria, which may facilitate earlier diagnosis of this disorder. We present evidence for an overlapping phenotype with the Laurence-Moon syndrome and propose a unifying, descriptive label be adopted (polydactyly-obesity-kidney-eye syndrome). We report an increased prevalence of renal malformations and renal cell carcinoma in the unaffected relatives of BBS patients and suggest that these may be a consequence of heterozygosity for BBS genes. Our findings have important implications for the care of BBS patients and their unaffected relatives.