Bardet–Biedl syndrome is a pleiotropic disorder with variable expressivity and a wide range of clinical variability observed both within and between families. The main clinical features are rod–cone dystrophy, with childhood-onset visual loss preceded by night blindness; postaxial polydactyly; truncalobesity that manifests during infancy and remains problematic throughout adulthood; specific learning difficulties in some but not all individuals; male hypogenitalism and complex female genitourinary malformations; and renal dysfunction, a major cause of morbidity and mortality. There is a wide range of secondary features that are sometimes associated with BBS including
"Brachydactyly/syndactyly of both the hands and feet is common, as is partial syndactyl (most usually between the second and third toes)"
"Developmental delay: Many children with BBS are delayed in reaching major developmental milestones including gross motor skills, fine motor skills, and psychosocial skills (interactive play/ability to recognize social cues)". However these delays are treatable with therapy.
The first known case was reported by Laurence and Moon in 1866 at the Ophthalmic Hospital in South London. Laurence–Moon–Biedl–Bardet syndrome are no longer considered as valid terms in that patients of Laurence and Moon had paraplegia but no polydactyly and obesity, which are the key elements of the Bardet–Biedl syndrome. Laurence–Moon syndrome is usually considered a separate entity. However, some recent research suggests that the two conditions may not be distinct.
As of 2012[update], 14 (or 15) different BBS genes have been identified.
Behavior and performance: a wide variety of socialization and social interaction problems have been identified with BBS. Some refer to it as a kind of "mild-Autism." Many children who are later (explicitly and formally) diagnosed with the syndrome have gone through an extended period of time where school and medical professionals have struggled to find a name for the child's problems over several years.
Defective thermosensation or mechanosensation. New finding reported in October 2007: "hitherto unrecognized, but essential, role for mammalian basal body proteins in the acquisition of mechano- and thermosensory stimuli [highlight potential] clinical features of ciliopathies in humans."
Additional features: Obesity, possibly related to a decreased sensory function that would normally indicate satiation. Hyperphagia in some patients.
The detailed biochemical mechanism that leads to BBS is still unclear.
The gene products encoded by these BBS genes, called BBS proteins, are located in the basal body and cilia of the cell.
Using the round worm C. elegans as a model system, biologists found that BBS proteins are involved in a process called Intraflagellar transport (IFT), a bi-directional transportation activity within the cilia along the long axis of the ciliary shaft that is essential for ciliogenesis and the maintenance of cilia. Recent biochemical analysis of human BBS proteins revealed that BBS proteins are assembled into a multiple protein complex, called "BBSome". BBSome is proposed to be responsible for transporting intracellular vesicles to the base of the cilia and to play an important role in the ciliary function.
Since abnormalities of cilia are known to be related to a wide range of disease symptoms including those commonly seen in BBS patients, it is now widely accepted that mutated BBS genes affect normal cilia functions, which, in turns, causes BBS.
A theory that photoreceptor cells are nourished by the IFT of retinal cilia now offers a potential explanation for the retinal dystrophy common in BBS patients after their early years of life.
^Ansley SJ, Badano JL, Blacque OE, Hill J, Hoskins BE, Leitch CC, Kim JC, Ross AJ, Eichers ER, Teslovich TM, Mah AK, Johnsen RC, Cavender JC, Lewis RA, Leroux MR, Beales PL, Katsanis N (October 2003). "Basal body dysfunction is a likely cause of pleiotropic Bardet–Biedl syndrome". Nature425 (6958): 628–33. doi:10.1038/nature02030. PMID14520415.