Bardet-Biedl syndrome

Laurence-Moon-Biedl syndrome and Laurence-Moon-Biedl-Bardet redirect here. See below for an explanation.

The Bardet-Biedl syndrome is a human genetic disorder that produces many effects and affects many body systems. It is characterized mainly by obesity, retinitis pigmentosa, polydactyly, mental retardation, hypogonadism, and renal failure in some cases.^[1]

Eponym and classification

The syndrome is named after Georges Bardet and Arthur Biedl.^[2]

Two forms have been identified:

• Bardet-Biedl syndrome 1 (BBS1) is mapped to markers on chromosome 11
• Bardet-Biedl syndrome 2 (BBS2) is mapped to markers on chromosome 16

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 the syndrome. Laurence-Moon syndrome is usually considered a separate entity. However, some recent research suggests that the two conditions may not be distinct.^[3]

Major clinical features

• Eyes: Pigmentary retinopathy, poor visual acuity, low vision, and/or blindness.
• Nose: Loss of, or reduced sense of, smell. (anosmia). Some patients claim extra-sensitive sense of smell. ^[4]
• Hand and foot: Polydactyly (extra digits) or syndactyly (webbing of fingers and toes).
• Cardiovascular system: Hypertrophy of interventricular septum and left ventricle and dilated cardiomyopathy.
• Gastrointestinal system: Fibrosis.
• Urogenital system: Hypogonadism, renal failure, urogenital sinuses, ectopic urethra, uterus duplex, septate vagina, and hypoplasia of the uterus, ovaries, and fallopian tubes.
• Growth and development: Mental and growth retardation.
• 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."^[5]
• Additional features: Obesity, possibly related to a decreased sensory function that would normally indicate satiation.

Pathophysiology

The detailed biochemical mechanism that leads to BBS is still unclear. At this moment, twelve genes (BBS1 to BBS12) that are responsible for the disease when mutated, have been cloned. The gene products encoded by these BBS genes, called BBS proteins, are located in the basal body and cilia of the cell.^{[citation needed]}

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 are essential for the formation and maintenance of cilia^[6]. 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 roles 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, cause BBS.^{[citation needed]}

Relation to other rare genetic disorders

Recent findings in genetic research have suggested that a large number of genetic disorders, both genetic syndromes and genetic diseases, that were not previously identified in the medical literature as related, may be, in fact, highly related in the genetypical root cause of the widely-varying, phenotypically-observed disorders. BBS is one such syndrome that has now been identified to be caused by defects in the cellular ciliary structure. Thus, BBS is a ciliopathy. Other known ciliopathies include primary ciliary dyskinesia, polycystic kidney and liver disease, nephronophthisis, Alstrom syndrome, Meckel-Gruber syndrome and some forms of retinal degeneration^[7].

Hereditary characteristics

The syndrome is familial and is transmitted as an autosomal recessive trait. chromosome 3 locus appears to be linked to polydactyly of all four limbs, whereas chromosome 15 is associated with early-onset morbid obesity and is mostly confined to the hands, and chromosome 16 represents the "leanest" form.^{[citation needed]}

Notes

1. ^ Beales P, Elcioglu N, Woolf A, Parker D, Flinter F (1999). "New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey". J. Med. Genet. 36 (6): 437–46. PMID 10874630. 
2. ^ synd/3745 at Who Named It
3. ^ Moore S, Green J, Fan Y et al (2005). "Clinical and genetic epidemiology of Bardet-Biedl syndrome in Newfoundland: a 22-year prospective, population-based, cohort study". Am. J. Med. GenetARRAY 132 (4): 352–60. doi:10.1002/ajmg.a.30406. PMID 15637713. 
4. ^ Downer, Joanna (2004-09-13). "That Stinks: People with Rare Obesity Syndrome Can't Sense Odors". The JHU Gazette. Johns Hopkins University. Retrieved on 2008-07-14.
5. ^ Tan PL, Barr T, Inglis PN, et al (2007). "Loss of Bardet Biedl syndrome proteins causes defects in peripheral sensory innervation and function". Proc. Natl. Acad. Sci. U.S.A. 104 (44): 17524–9. doi:10.1073/pnas.0706618104. PMID 17959775. PMC:2077289. Retrieved on 2008-07-14.  }}
6. ^ Blacque OE, Reardon MJ, Li C, McCarthy J, Mahjoub MR, Ansley SJ, Badano JL, Mah AK, Beales PL, Davidson WS, Johnsen RC, Audeh M, Plasterk RH, Baillie DL, Katsanis N, Quarmby LM, Wicks SR, Leroux MR. (2004). "Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport.". Genes Dev. 18: 1630-42. PMID 15231740. 
7. ^ Badano JL, Mitsuma N, Beales PL, Katsanis N (2006). "The ciliopathies: an emerging class of human genetic disorders". Annu Rev Genomics Hum Genet 7: 125–48. doi:10.1146/annurev.genom.7.080505.115610. PMID 16722803. 

External links

• Laurence Moon Bardet Biedl Society (UK-based)
• LMBBS Association (US-based)
• The Importance of Being Cilia Accessible article at Howard Hughes Medical Institute on the importance and extensive use of cilia and basal bodies in many organ systems of human physiology. Includes multiple specific mentions of BBS.
• BBS and loss of the sense of smell at Johns Hopkins University
• Overview at United States National Library of Medicine
• Foundation Fighting Blindness
• Bardet-Biedl Syndrome Association francaise (France-based; in French language) Syndrome de Bardet-Biedl (BBS)