Laurence Moon Bardet Biedl Society
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LMBBS Laurence Moon Bardet Biedl Society |
The latest article to appear in a medical journal was written by Dr Philip Beales in conjuction with others including our very own Drina Parker. It is detailed below and a pdf version of the paper can be found at the Journal Of Medical Genetics (J Med Genet 1999;36:437-446)
Abstract
Bardet-Biedl syndrome (BBS) is an autosomal recessive condition characterised by rod-cone dystrophy, postaxial polydactyly, central obesity, mental retardation, hypogonadism, and renal dysfunction. BBS expression varies both within and between families and diagnosis is often difficult. We sought to define the condition more clearly by studying 109 BBS patients and their families, the largest population surveyed to date. The average age at diagnosis was 9 years, which is late for such a debilitating condition, but the slow development of the clinical features of BBS probably accounts for this. Postaxial polydactyly had been present in 69% of patients at birth, but obesity had only begun to develop at around 2-3 years, and retinal degeneration had not become apparent until a mean age of 8.5 years. Our study identified some novel clinical features, including neurological, speech, and language deficits, behavioural traits, facial dysmorphism, and dental anomalies. In the light of these features we propose a revision of the diagnostic criteria, which may facilitate earlier diagnosis of this disorder. We present evidence for an overlapping phenotype with the Laurence-Moon syndrome and propose a unifying, descriptive label be adopted (polydactyly-obesity-kidney-eye syndrome). We report an increased prevalence of renal malformations and renal cell carcinoma in the unaffected relatives of BBS patients and suggest that these may be a consequence of heterozygosity for BBS genes. Our findings have important implications for the care of BBS patients and their unaffected relatives.
(J Med Genet 1999;36:437-446) Keywords: Bardet-Biedl syndrome; diagnosis; renal malformation; heterozygotes
Thanks largely to members of the Society completing a comprehensive questionnaire, Dr Philip Beales' 1997 survey on LMBB Syndrome proved to be the most significant survey on the Syndrome that has ever been conducted. Surveys such as this are important to all concerned in building up accurate knowledge of the Syndrome, particularly for the medical profession and carers. Following Dr Beales' successful survey, last July we published the most comprehensive description ever produced of Laurence-Moon-Bardet-Biedl Syndrome in the medical booklet More than Meets the Eye.
Dr. Phil Beales, the Society's medical adviser has succeeded in securing a 3-year grant from The Wellcome Foundation to fund research into LMBB Syndrome. He will be working in Houston for 12 months with Dr. Richard Lewis. This raises the profile of LMBB Syndrome and gives recognition to the work of Dr. Beales into every aspect of LMBB Syndrome - gene mapping, research studies and the management of the many symptoms associated with the Syndrome.
Since the first papers describing the rough location (i.e. which part of which human chromosome the genes are likely to reside on) were published in 1993, very little advancement towards identifying the exact locations of the BBS genes has taken place. This is probably due to a combination of the rarity of BBS (and so relatively few large families to study) and evidence for the existence of up to 6 different genes (each one cannot be differentiated on clinical grounds alone). In fact the locations of five BBS genes have been published and designated BBS1-5 (on chromosomes 11q13, 16q21, 3p13, 15q23 and 2q13 respectively). To address the problem of resources, in 1998 the International Bardet-Biedl Syndrome Consortium was established. The consortium comprises labs from three countries; the USA (Baylor College of Medicine, Texas), Canada (Memorial University, Newfoundland) and the United Kingdom (Guys Hospital/Institute of Child Health, London) and its main purpose is to pool family resources, data and technical know-how and to avoid duplication of work. Recently, the Wellcome Trust (UK) has considered molecular genetic research into BBS to be an important area worthy of funding. The award of a Wellcome Advanced Fellowship has enabled me to move for the first year (of three), to Houston, Texas to work with Dr. Nico Katsanis in the labs of Professor Jim Lupski and Professor Richard Lewis. Together we have been concentrating on identifying the gene on 11q13 as both our groups have shown that this appears to responsible for up to half of all cases of BBS in Europe and North America. Already this has proved to be a fruitful collaboration in that we have been able to reduce the area in which the gene lies by at least 10 fold, a prerequisite to identifying the gene itself. This homing-in process has allowed us to focus on a handful of genes already known to exist in the area but whose function is unknown - any one of these may be the BBS gene. By a painstaking process of searching through the genetic code of each of these candidate genes letter-by-letter, we are gradually getting closer to our target. Many new genes are also being discovered (nothing to do with BBS) at the same time giving the whole exercise further meaning. We envisage the responsible gene on 11q13 to be something completely new which might be part of a novel biological pathway, parts of which may be switched on and off at different times during organ development. Other components of this pathway might be coded by the other genes (BBS2-4 on different chromosomes) thus completing the picture. However, finding the correct gene(s) is only the beginning of our understanding how/why the problems associated with BBS come about. The experiments to answer these questions will keep us (and others) busy for years to come. In the short term, however, identification of the causative genes will provide us with a diagnostic test and a prenatal test in those families already affected by BBS (if they so wish). Ultimately, treatment and amelioration of at least part of the Syndrome is our aim, but this can only be achieved by first understanding how the condition arises.
Dr. Philip L. Beales, August 1999
We have a link to Dr. Beales' LMBBS website on our links page
Note: BBS is a common abbreviation for LMBBS
As all people with LMBB Syndrome know, controlling weight is a major issue and thankfully some research is currently being undertaken by the Royal London Hospital.
Many people with LMBBS experience difficulties controlling their weight, with a recent estimate suggesting just over 75% of the UK LMBBS population are obese. Despite such a high frequency of obesity, little is known about the underlying causes. It is unclear whether weight gain occurs due to enhanced hunger sensations and corresponding high food intake or whether there is a defective metabolism resulting in lower calories requirements. The aim of this study is to measure the calorie needs of people with LMBBS, examining reported food intakes, resting metabolism, body composition and the role of physical activity in the development and maintenance of obesity. It is hoped that this will enhance our understanding of the causes of obesity in LMBBS and thus may provide greater insight into the most appropriate management strategies.
Clare Grace SRD MSc, September 1999
We hope to report on more research items here as they happen.