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

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.

Skin manifestations of Bardet–Biedl syndrome

“…Another reported obesity‐ and diabetes‐related skin complication is acanthosis nigricans 7 . Moreover, atopic diathesis seems to be particularly frequent in patients with BBS (up to 25% of asthma prevalence) 8 and may yield an increased occurrence of atopic dermatitis, which was present in our patient’s history.…”

“…Other mucocutaneous manifestations sporadically described in BBS are purpura in the setting of idiopathic thrombocytopenic purpura, 9 anocutaneous fistula, 10 multiple melanocytic nevi (in up to 20% of patients), 8,11 lymphangioma, 12 and gingival hyperplasia 13 …”

Ophthalmic and Genetic Features of Bardet Biedl Syndrome in a German Cohort

“…Two years later, in 1922, Artur Biedl reported on a "Sibling pair with adiposo-genital dystrophy, along with illustrations of a third case" [2]. Both papers describe a syndrome that was subsequently named the Bardet-Biedl syndrome (BBS, OMIM 2099000), a form of the similar manifesting Laurence-Moon syndrome [3], although there is research suggesting that the two conditions are not distinct, but variable expressions of the same disease [4][5][6][7]. Therefore, the disorder is sometimes also acknowledged as Laurence-Moon-Bardet-Biedl syndrome.…”

Allelic overload and its clinical modifier effect in Bardet-Biedl syndrome

“…The inclusion criteria for families was a genetic diagnosis of BBS in at least one affected member. Available clinical and familial data were extracted for each patient and reviewed through medical reports, questionaries, and/or electronic health records, as previously described 38,50 .…”