Bardet-Biedl Syndrome

Bardet-Biedl Syndrome (BBS) is a pleiotropic autosomal recessive disorder. This clinically complex genetically heterogeneous disorder is associated with mostly monogenic causes. BBS is a rare condition and is said to occur in 1 in every 150,000 persons born in the population.

The syndrome is defined by a range of primary and secondary features including retinitis pigmentosa, retinopathy, obesity (early-onset morbid obesity is associated with abnormalities chromosome 15), hypogonadism, renal dysfunction, postaxial polydactyly (said to be linked to abnormalities in chromosome 3), and mental retardation. Other manifestations include diabetes mellitus, heart disease, hepatic fibrosis, neurological abnormalities, reproductive abnormalities, endocrine disturbances, short stature, myopia, strabismus, and cataracts. Individuals may also have partial or complete anosmia due to loss of function of the BBS protein which affects the olfactory epithelium.

Patients often experience a late onset of symptoms and, thus, the diagnosis of BBS is usually made during childhood. Obesity appears around age 2–3 years in the patient; however, as this is not diagnostic of the disorder, the actual disorder is diagnosed at approximately 9 years of age when visual problems first appear.

BBS may be occur due to mutations in certain genes (BBS1, BBS2, BBS3 (ARL6), BBS4, BBS5, BBS6 (MKKS), BBS7, BBS8 (TTC8), BBS9, BBS10, BBS11, BBS12). All these gene codes for proteins are associated with the centrioles part of the cytoskeletal system and play a role in cilia function. BBS is possibly caused by a defect of the basal body of ciliated cells. BBS1 is caused by mutation in a gene that maps to chromosome 11q13. The BBS1 is associated with the greatest occurrence of the disorder followed by BBS2. BBS2 is caused by mutation in a gene that maps to chromosome 16q21. BBS3 is caused by mutation in the ADP-ribosylation factor (ARF)-like-6 gene (ARL6) on chromosome 3p13-p12. BBS4 is caused by mutation in a gene that maps to chromosome 15q22.3-q23. BBS5 is caused by mutation in a gene that maps to chromosome 2q31. BBS6 is caused by mutation in MKKS, located on 20p12. BBS7 is caused by mutation in a gene that maps to chromosome 4q27. BBS8 is caused by a mutation in a tetratricopeptide repeat protein, TTC8. The BBS8 gene mutations encodes a protein [Page 73]with a prokaryotic domain, pilF; this is involved in pilus formation and twitching mobility. BBS9 is caused by mutation in the parathyroid hormone-responsive gene B1 (PTHB1). BBS10 is caused by mutation in the C12ORF58 gene. Mutation in the tripartite motif-containing protein-32 gene (TRIM32) BBS11. Mutation in the C4ORF24 gene causes BBS12. Reports suggest that the BBS genes may predispose male heterozygote patients to obesity.

There has been long-standing uncertainty as to the relationship between the Laurence-Moon syndrome and BBS. Patients suffering from these disorders report similar symptoms and, thus, it was previously difficult to distinguish between the two disorders. However, it is generally reported that the patients of Laurence and Moon have a distinct disorder with paraplegia and without polydactyly and obesity.

The prognosis for BBS varies according to the severity of symptoms, visual prognosis is poor and complication of obesity and renal impairment may increase morbidity and mortality rates.

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