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At a glance

A congenital ciliopathy with pigmentary retinopathy, renal and cardiac anomalies, diabetes mellitus (DM), severe obesity, polydactyly, and hypogonadism.

Synonyms

Biedl Syndrome. Often incorrectly called (and confused with) Laurence-Moon-Bardet-Biedl Syndrome. Laurence-Moon Syndrome (LMS) and BBS may share many similarities, but when compared to BBS, LMS typically presents with spastic paraplegia, choroideremia rather than cone-rod dystrophy and absence of polydactyly. LMS seems to be caused by mutations in the PNPLA6 (patatin-like phospholipase domain-containing protein 6) gene, which has been mapped to chromosome 19p13.2. The discussions if BBS and LMS are the same disorder with variable manifestation or are indeed separate entities is ongoing, but here we decided to treat them as different diseases.

Incidence

Sex ratio is 1:1. An increased incidence has been found in the Arab population of Kuwait (among the Bedouins) with an estimated (minimal) prevalence of 1:13,500 and in Newfoundland (Canada) with 1:18,000. In people of European descent, the prevalence is in the range of 1:160,000.

Genetic inheritance

Autosomal recessive or digenic recessive. Consanguinity of parents is common. BBS is a genetically very heterogeneous disorder and more than 20 different types have been described. BBS-1 is the most common type (approximately one quarter of BBS patients) with the defect mapped to chromosome 11q13. Some patients with mutations in one of the BBS genes also have mutations in other genes, which may modify or alter the manifestation of the disorder and explain, at least in part, the wide phenotypic variability. Heterozygotes have an increased frequency of obesity, hypertension, DM, and renal disease. There is an increased prevalence of renal malformations and renal clear cell adenocarcinoma in unaffected relatives of BBS patients, which might be due to heterozygosity for the BBS genes.

Pathophysiology

Almost all epithelial cells are ciliated. Cilia can be distinguished according to their function and structure as either primary cilia or motile cilia/flagella. Independent of the type though, these cilia consist of a basal body underneath the cell surface and an axoneme (the central strand of the cilium consisting of microtubules) that extends away from the cell membrane, typically projecting into the lumen of a tube or tubule. Being exposed to the luminal contents, the cilia are able to sense and then signal information to other cells for example by releasing soluble factors. Primary cilia are now increasingly recognized as important cell components that may act as chemo- and/or mechanosensors in the extracellular environment. Several disorders are now considered caused by anomalies of the cilia and are therefore called ciliopathies (see “Other conditions to be considered”).

Diagnosis

Based on the six cardinal signs of the syndrome, which are renal dysfunction, truncal obesity, hypogonadism, polydactyly, learning disabilities, and retinal dystrophy.

Clinical aspects

The different types ...

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