Bardet-Biedl syndrome (BBS) clinically presents with retinal degeneration, limb abnormalities (polydactyly, brachydactyly), obesity (hyperphagia), developmental delay, reproductive anomalies and renal/ urinary tract abnormalities that may lead to renal failure as cardinal features. There is a broad spectrum of additional clinical symptoms accompanying the above mentioned features (e.g. neurological abnormalities, hearing problems, dental anomalies, cardiac anomalies and diabetes mellitus) that are reported in some patients with BBS. The reported prevalence of BBS varies considerably regionally between 1:13500 (Kuwait, Newfoundland) and 1:160000 (northern Europe population) [1;2].
BBS is a mostly autosomal recessive inherited genetic disease. 18 BBS genes are know so far, most of the genes encode for proteins in the basal body of primary ciliae . Additional modifiers are reported in several cases, that addtionally complicate the path of heredity. [4-7].
Primary cilia have a broad tissue distribution and are present on most cell types in the human body. Originally considered to be redundant, research over the past years describe them as evolutionarily conserved organelles, that play an decisive role in mammalian development. They are located at cell surfaces and play a significant role in whole-cell locomotion; movement of fluid; chemo-, mechano-, and photosensation; and sexual reproduction. Defects in cilia are associated with a range of human diseases, such as primary ciliary dyskinesia, hydrocephalus, polycystic liver and kidney disease, and retinal degeneration.
Epidemiologic studies on BBS including a high number of patients are rare, mostly emphasizing on adults with BBS. Knowledge about childhood, especially in the first years of life, is rudimentary, more frequently presented in small-scale cases. Apart from observing the occurrence and development of main cardinal features of BBS information about growth, onset of puberty, psychomotor development is not observed systematically.
known genes for BBS
|Disease||OMIM Phenotype Nr||Gene||OMIM – Gene number||alternative Phenotype + OMIM Phenotype Nr|
|2||BBS2||615981||BBS2||606151||Retinitis pigmentosa 74||616562|
|3||BBS3||600151||ARL6||608845||Retinitis pigmentosa 55||613575|
|8||BBS8||615985||TTC8||608132||Retinitis pigmentosa 51||613464|
|21||BBS21||617406||C8orf37||614477||Retinitis pigmentosa 64||614500|
- 1 Beales PL, Elcioglu N, Woolf AS, Parker D, Flinter FA: New criteria for improved diagnosis of Bardet–Biedl syndrome: results of a population survey. J Med Genet 1999; 36: 437–446.
- 2 Moore SJ, Green JS, Fan Y et al: Clinical and genetic epidemiology of Bardet-Biedl syndrome in Newfoundland: a 22-year prospective, population-based, cohort study. Am J Med Genet A 2005; 132: 352–360.
- 3 Zaghloul NA, Katsanis N: Mechanistic insights into Bardet-Biedl syndrome, a model ciliopathy. J Clin Invest 2009; 119: 428–437.
- 4 Katsanis N, Ansley SJ, Badano JL et al: Triallelic inheritance in Bardet–Biedl syndrome, a Mendelian recessive disorder. Science 2001; 293: 2256–2259.
- 5 Eichers ER, Lewis RA, Katsanis N, Lupski JR: Triallelic inheritance: a bridge between Mendelian and multifactorial traits. Ann Med 2004; 36: 262–272.
- 6 Beales PL, Badano JL, Ross AJ et al: Genetic interaction of BBS1 mutations with alleles at other BBS loci can result in non-Mendelian Bardet-Biedl syndrome. Am J Hum Genet 2003; 72: 1187–1199.
- 7 Badano JL, Kim JC, Hoskins BE et al: Heterozygous mutations in BBS1, BBS2 and BBS6 have a potential epistatic effect on Bardet-Biedl patients with two mutations at a second BBS locus. Hum Mol Genet 2003; 12: 1651–1659.
- 8 Obesity in patients with Bardet-Biedl syndrome: influence of appetite-regulating hormones.
Büscher AK, Cetiner M, Büscher R, Wingen AM, Hauffa BP, Hoyer PF.
Pediatr Nephrol. 2012 Nov;27(11):2065-71.