Bardet-Biedl syndrome: BBS; Laurence-Moon-Bardet-Biedl syndrome

The syndrome is a rare inherited condition which is variable in the way in which it presents. Characteristics are: rod/cone dystrophy (atypical retinitis pigmentosa - a progressive eye condition which can lead to blindness (see entry Visual Impairment)); obesity (usually with an early onset and resistant to treatment); polydactyly (extra fingers and/or toes); hypogenitalism (underdeveloped genitals); mild to severe learning difficulties; and kidney malformations and renal dysfunction. Usually four out of these six features are required to make the diagnosis. In addition, there are other important characteristics which need to be considered: developmental delay; speech difficulties; olfactory deficits (diminished ability to smell); diabetes mellitus; diabetes insipidus; hepatic fibrosis; and hormonal deficiencies (e.g. thyroid, testosterone).

In the Middle-East and island communities such as Newfoundland, the condition is relatively common, occurring at rates of 1 in 13,500 of the population. In Europe and the UK the prevalence is much less common owing to lower consanguinity. The figure is probably between 1 in 70,000 to 100,000 of the population. Although BBS is not common it is certainly under diagnosed. As awareness of the condition increases, the number of people identified is growing every year.

Inheritance patterns
For the majority of cases, inheritance is autosomal recessive. Although in a few cases, more than two mutations in two BBS genes may be required to manifest the condition ("triallelic inheritance"). Nine different gene defects have been shown to be responsible for the majority of cases and more are postulated. They are located on different chromosomes: BBS1 on chromosome 11 (long arm); BBS2 on chromosome 16 (long arm); BBS3 on chromosome 3 (short arm); BBS 4 on chromosome 15 (long arm); BBS5 on chromosome 2 (long arm); and most recently, BBS6 on chromosome 20 (short arm); BBS7 on chromosome 4 (long arm); BBS8 on chromosome 14 (long arm); and BBS9 on chromosome 7 (short arm). BBS1 accounts for approximately fifty per cent of cases seen in Britain and BBS2 is the second most prevalent gene.

Despite the identification of nine genes, these still only account for around forty-five per cent of all cases to date indicating that there are several more genes left to find. Nonetheless, their discovery has, in the last few years, led to an explosion in our understanding of the underlying cellular problem. It seems the problems lies in function of the cilium, a long, thin appendage that sticks out of the surface of most cells in our body and serves to sense the surrounding environment. Research is moving quickly to find out exactly what has gone wrong in the cells and the organs which they make up. This will ultimately help in the design of new diagnostic tests and perhaps therapeutic strategies. Although a sizeable proportion of families affected by BBS can now be offered gene testing in theory, simple genetic assays still need to be developed as the genes are large and looking for mutations takes time and is costly. Diagnosis is still based on clinical manifestations but molecular analysis may help confirm this in doubtful cases.

Prenatal diagnosis
A number of features can be determined on high definition ultrasound scanning of the fetus. In particular, the number of fingers and toes may be counted and specific kidney malformations seen. This, however, is not a test of exclusion of the condition. If two gene mutations can be identified in a BBS family then a molecular genetic test can be offered prenatally.

Medical text written January 1996 by Dr P L. Beales. Last updated October 2005 by Professor P L. Beales, Professor of Medical and Molecular Genetics, Wellcome Trust Senior Research Fellow in Clinical Science, Consultant in Clinical Genetics, Molecular Medicine Unit, Institute of Child Health, London, UK.

Further Online Resources
Medical texts in The Contact a Family Directory are designed to give a short, clear description of specific conditions and rare disorders. More extensive information on this condition can be found on a range of reliable, validated web sites and links to them are included in the CD-ROM version of this Directory. Further information on these resources can be found in our Medical Information on the Internet article.

LMBB SOCIETY

LMBB Society
10 High Cross Road
Rogerstone
Newport NP10 9AD
Tel: 01633 718415
e-mail: chris.humphreys4@ntlworld.com
Web: http://www.lmbbs.org.uk

The Society is a National Registered Charity No. 1027384, established in 1987. It offers: support and advice to families by telephone, letter and email; and contact with other families. Activities include raising awareness of the condition, an annual family conference and fundraising. It publishes a twice yearly newsletter in print and on audio cassette. It has information available, details on request. The Society represents over 200 families.

Group details last confirmed January 2007.