Bardet- Biedl syndrome (BBS) is a rare syndromic disorder with a wide spectrum of clinical manifestations. Retinal degeneration, polydactyly, obesity, learning impairment, hypogonadotropic hypogonadism and renal abnormalities are considered the cardinal clinical features. Secondary features include syndactyly/brachydactyly, diabetes mellitus, behavioural abnormalities, ataxia-poor coordination, anosmia, oral/dental, gastrointestinal, endocrine/metabolic, cardiovascular and thoraco-abdominal abnormalities. The clinical diagnosis requires the presence of either four major features or three major and two minor features. The disease has an autosomal recessive inheritance and can be caused by mutations in at least 26 different genes.
Prevalence
The prevalence of BBS varies among different geographic areas, with a higher frequency in subpopulations and relatively closed geographic areas. In North America and Europe, it ranges between 1:120.000 and 1:160.000 individuals. To date, there is no gender bias.
Main clinical features
Individuals with BBS generally have retinal cone-rod dystrophy, central obesity, postaxial polydactyly, cognitive impairment, kidney disease, hypogonadism and genitourinary abnormalities. Less common defects have been described, as stated above.
Molecular features
BBS is caused by homozygous or compound heterozygous mutations in 26 different genes; BBS1 is one of the most common causative genes in western countries. Almost all BBS proteins localize to the basal body of the primary cilia, thus the disorder is considered a component of the heterogenous group of disorders known as ciliopathies.
Inheritance and genetic counselling
BBS is inherited in an autosomal recessive manner. Thus, parents are typically asymptomatic carriers of single copies of disease mutation. Their children have a 25% risk of inheriting both maternal and paternal disease mutations, leading to disease onset.
Management
To date, there is no specific therapy and patients need supportive treatment. Because of the systemic involvement, a multidisciplinary approach and a personalized follow-up are required.