Clinical and genetic epidemiology of Bardet-Biedl syndrome in Newfoundland: A 22-year prospective, population-based, cohort study

Abstract

Bardet-Biedl syndrome (BBS) and Laurence-Moon syndrome (LMS) have a similar phenotype, which includes retinal dystrophy, obesity, and hypogenitalism. They are differentiated by the presence of spasticity and the absence of polydactyly in LMS. The aims of this study were to describe the epidemiology of BBS and LMS, further define the phenotype, and examine genotype-phenotype correlation. The study involved 46 patients (26 males, 20 females) from 26 families, with a median age of 44 years (range 1-68 years). Assessments were performed in 1986, 1993, and 2001 and included neurological assessments, anthropometric measurements, and clinical photographs to assess dysmorphic features. The phenotype was highly variable within and between families. Impaired co-ordination and ataxia occurred in 86% (18/21). Thirty percent (14/46) met criteria for psychiatric illness; other medical problems included cholecystectomy in 37% (17/46) and asthma in 28% (13/46). Dysmorphic features included brachycephaly, large ears, and short, narrow palpebral fissures. There was no apparent correlation of clinical or dysmorphic features with genotype. Two patients were diagnosed clinically as LMS but both had mutations in a BBS gene. The features in this population do not support the notion that BBS and LMS are distinct. The lack of a genotype-phenotype correlation implies that BBS proteins interact and are necessary for the development of many organs.

Bardet–Biedl syndrome

“…4,6,[14][15][16][17] Birth weight is usually within the normal range, although there is an evidence of a skewed distribution towards the upper centiles. 18 One-third of those with a normal birth weight develop obesity by the age of one.…”

“…4,17,19 This may occur independently or in conjunction with biochemical hypogonadism. A wide variety of genital malformations have been observed in females, contributing to the low rates of fertility in BBS.…”

“…4 Children with BBS are often reported to have labile behaviour with outbursts of frustration. 4,17,19 Many prefer to have a fixed routine and may have elements of obsessive compulsive behaviour and lack of social dominance. 4 Others have a more severe behavioural phenotype and develop autistic spectrum disorder or psychosis.…”

BBS6, BBS10, and BBS12 form a complex with CCT/TRiC family chaperonins and mediate BBSome assembly

“…More specifically, it is unknown (i) whether these chaperonin-like BBS proteins interact with each other and form a multisubunit complex or function individually in a common, linear pathway, (ii) whether they indeed have molecular chaperone function, and (iii) if so, which proteins/processes are regulated by these proteins. In addition, although chaperoninlike BBS proteins are not components of the BBSome, the phenotypes of Bbs6 null mice and human patients with mutations in BBS6, BBS10, or BBS12 genes are similar to mice and human patients with mutations in BBSome components (6,(8)(9)(10). The overlap in phenotypes implies that the functions of chaperoninlike BBS proteins are closely related to those of other BBS proteins.…”

End Stage Renal Disease, Differential Diagnosis, A Rare Genetic Disorder: Bardet–Biedl Syndrome: Case Report and Review

“…3. Truncal Obesity: Obesity was reported in 72% of cases [12]. Defects in leptin action may be responsible for the development of obesity in BBS.…”