Bardet-Biedl syndrome: Difference between revisions

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{{CMG}} {{AE}} {{AN}}
{{CMG}} {{AE}} {{AN}}


{{SK}} Laurence-Moon-Biedl syndrome; Laurence-Moon-Biedl-Bardet; LMBBS; LMBS
{{SK}} Laurence-Moon-Biedl syndrome; Laurence-Moon-Biedl-Bardet; LMBBS; LMBS;BBS


==Overview==
==Overview==
Line 32: Line 32:


==Pathophysiology==
==Pathophysiology==
*The detailed biochemical mechanism that leads to BBS is still unclear.
*Even though the detailed biochemical mechanism that leads to BBS is unclear, the syndrome is thought to result largely from a defect in basal body of ciliated cells.
*The gene products encoded by these ''BBS'' genes, called BBS proteins, are located in the [[basal body]] and [[cilia]] of the [[Cell (biology)|cell]].<ref name="pmid14520415">{{cite journal | author = Ansley SJ, Badano JL, Blacque OE, Hill J, Hoskins BE, Leitch CC, Kim JC, Ross AJ, Eichers ER, Teslovich TM, Mah AK, Johnsen RC, Cavender JC, Lewis RA, Leroux MR, Beales PL, Katsanis N | title = Basal body dysfunction is a likely cause of pleiotropic Bardet–Biedl syndrome | journal = Nature | volume = 425 | issue = 6958 | pages = 628–33 | year = 2003 | month = October | pmid = 14520415 | doi = 10.1038/nature02030 | url = | issn = }}</ref>
*The gene products encoded by these ''BBS'' genes ({{Gene|BBS1}} to {{Gene|BBS8}}, called BBS proteins, are located in the [[basal body]] and [[cilia]] of the [[Cell (biology)|cell]].<ref name="pmid14520415">{{cite journal | author = Ansley SJ, Badano JL, Blacque OE, Hill J, Hoskins BE, Leitch CC, Kim JC, Ross AJ, Eichers ER, Teslovich TM, Mah AK, Johnsen RC, Cavender JC, Lewis RA, Leroux MR, Beales PL, Katsanis N | title = Basal body dysfunction is a likely cause of pleiotropic Bardet–Biedl syndrome | journal = Nature | volume = 425 | issue = 6958 | pages = 628–33 | year = 2003 | month = October | pmid = 14520415 | doi = 10.1038/nature02030 | url = | issn = }}</ref>
*Using the round worm ''[[Caenorhabditis elegans|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 is essential for [[ciliogenesis]] and the maintenance of cilia.<ref>{{cite journal| author=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.|title=Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport | journal= Genes Dev. | volume=18 | pages=1630–42 | year= 2004 | pmid=15231740| doi=10.1101/gad.1194004| issue=13| pmc=443524}}</ref> 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 role in the ciliary function.{{cn|date=July 2012}}
*Using the round worm ''[[Caenorhabditis elegans|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 is essential for [[ciliogenesis]] and the maintenance of cilia.<ref>{{cite journal| author=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.|title=Loss of C. elegans BBS-7 and BBS-8 protein function results in cilia defects and compromised intraflagellar transport | journal= Genes Dev. | volume=18 | pages=1630–42 | year= 2004 | pmid=15231740| doi=10.1101/gad.1194004| issue=13| pmc=443524}}</ref> 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 role in the ciliary function.{{cn|date=July 2012}}
*The syndrome is familial and is transmitted as an [[autosomal recessive]] trait. [[Chromosome 3 (human)|chromosome 3]] locus appears to be linked to [[polydactyly]] of all four limbs, whereas [[chromosome 15 (human)|chromosome 15]] is associated with early-onset morbid [[obesity]] and is mostly confined to the hands, and [[chromosome 16 (human)|chromosome 16]] represents the "leanest" form.
*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, causes BBS.{{Citation needed|date=June 2008}}
*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, causes BBS.{{Citation needed|date=June 2008}}
*Genes involved include:{{cn|date=July 2012}}
*Genes involved include:{{cn|date=July 2012}}
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</ref>
</ref>


==Major features==
==Differentiating Bardet-Biedl syndrome from other Diseases==
* Eyes: [[Retinitis pigmentosa]], [[poor visual acuity]], [[low vision]], and/or [[blindness]].
*Bardet–Biedl syndrome (BBS) and [[Laurence–Moon syndrome]] (LMS) have a similar phenotype, which includes retinal dystrophy, [[obesity]], and [[hypogenitalism]].
* Nose: Loss of, or reduced sense of, smell. ([[anosmia]])
*They are differentiated by the presence of [[spasticity]] and the absence of [[polydactyly]] in [[LMS]].
* Hand and foot: [[Polydactyly]] or [[syndactyly]] (webbing of fingers and toes).
*The overlapping features of these cases suggested that the two disorders represented variable expression of a single condition.
* Cardiovascular system: [[Organ hypertrophy|Hypertrophy]] of [[interventricular septum]] and [[left ventricle]] and [[dilated cardiomyopathy]].
*The findings of neurological manifestations in BBS patients has prompted hypotheses that [[LMS]] and [[BBS]] are allelic.<ref name="pmid15637713">{{cite journal |author=Moore SJ, Green JS, Fan Y, ''et al.'' |title=Clinical and genetic epidemiology of Bardet-Biedl syndrome in Newfoundland: a 22-year prospective, population-based, cohort study |journal=[[American Journal of Medical Genetics. Part a]] |volume=132 |issue=4 |pages=352–60 |year=2005 |month=February |pmid=15637713 |pmc=3295827 |doi=10.1002/ajmg.a.30406 |url=}}</ref>
* Gastrointestinal system: [[Fibrosis]].
* Urogenital system: [[Hypogonadism]], [[chronic 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.
* Heredity: The syndrome is familial and is transmitted as an [[autosomal recessive]] trait. [[Chromosome 3 (human)|chromosome 3]] locus appears to be linked to [[polydactyly]] of all four limbs, whereas [[chromosome 15 (human)|chromosome 15]] is associated with early-onset morbid [[obesity]] and is mostly confined to the hands, and [[chromosome 16 (human)|chromosome 16]] represents the "leanest" form.
* Additional features: [[Obesity]].


== Cause ==
==Epidemiology and Demographics==
The detail biochemical mechanism that leads to BBS is still unclear. Recently, eight genes ({{Gene|BBS1}} to {{Gene|BBS8}}) that are responsible for the disease when mutated have been cloned, and most of the gene products encoded by these ''BBS'' genes are located in the [[basal body]] and [[cilia]] of the cell. It has been postulated that these ''BBS'' gene products might involve in the cell signaling pathway in the cilia, and these signaling systems play an essential role in the normal development so that a malfunction in these systems causes the diverse pathological effects of the Syndrome.
*Bardet-Biedl syndrome has a prevalence of 1 in 125,000- 160,000 in Europe<ref name="pmid5367041">{{cite journal |author=Klein D, Ammann F |title=The syndrome of Laurence-Moon-Bardet-Biedl and allied diseases in Switzerland. Clinical, genetic and epidemiological studies |journal=[[Journal of the Neurological Sciences]] |volume=9 |issue=3 |pages=479–513 |year=1969 |pmid=5367041 |doi= |url=}}</ref>, whereas in Arab countries, it is about 1 in 165,000 population.<ref name="pmid3359670">{{cite journal |author=Farag TI, Teebi AS |title=Bardet-Biedl and Laurence-Moon syndromes in a mixed Arab population |journal=[[Clinical Genetics]] |volume=33 |issue=2 |pages=78–82 |year=1988 |month=February |pmid=3359670 |doi= |url=}}</ref>


In addition to so-called "signaling' along the cilia, it appears that [[Intraflagellar transport]] (IFT) of proteins along the cilia are essential for the formation and maintenance of healthy cells. In particular, abnormalities in retinal cilia are hypothesized to be related to the retinal dystrophy which is common in BBS patients.
==Diagnosis==
===Symptoms===
*[[Poor visual acuity]],
*[[Low vision]], and/or
*[[Blindness]].
*Loss of, or reduced sense of, smell. ([[anosmia]])
*[[Polydactyly]] or
*[[Syndactyly]] (webbing of fingers and toes).
*[[Systemic hypertension]] from [[Organ hypertrophy|hypertrophy]] of [[interventricular septum]] and [[left ventricle]] and [[dilated cardiomyopathy]]
*Menstrual irregularities e.g: [[amenorrhea]] may occur from low [[estrogen]] levels or [[hypogonadotropism]].
*Small testes and genitalia [[Hypogonadism]]
*[[Mental retardation]]:  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.
*[[Growth retardation]]
*[[Obesity]]
 
===Physical Examination===
==== Appearance of the Patient ====
*The patient appears [[obese]] and has a [[short stature]].
 
====Vital Signs====
*[[Blood pressure]] may be elevated.
 
==== Eyes ====
*[[Poor visual acuity]]
*[[Cataracts]] may be noted
*[[Nystagmus|End gaze nystagmus]]
*[[Fundoscopy]]:
**[[Retinitis pigmentosa]]
**Retinal dystrophy
 
====Nose====
*[[Anosmia]]
 
==== Heart ====
*Precordial examination:
**[[Thrill]] may be present.
*Auscultation:
**[[Ejection systolic murmur]] may be present.
**Machinery murmur from [[patent ductus arteriosus]] may be present.
**[[S3]] may be heard.
 
==== Extremities ====
*[[Polydactyly]]
*[[Syndactyly]]
 
==== Neurologic ====
*[[Mental retardation]]
*[[Learning disabilitites]]
 
====Genitourinary examination====
*[[Hypogonadism]]
*[[Cryptorchidism]]
*[[Microphallus]]
*Persistent [[urogenital sinus]], [[ectopic urethra]], [[hypoplasia]] of the [[uterus]], [[ovaries]], and [[fallopian tubes]]; uterus duplex; and [[septate vagina]], [[vaginal atresia]]
 
=== Laboratory Findings ===
*[[Normocytic normochromic anemia]] or [[iron deficiency anemia]]
*[[Serum creatinine]] levels may be raised from [[chronic renal failure]]
*Similarly, increase in [[serum urea]] and [[BUN]] levels may be noted.
*Endocrine abnormalities:
**Low [[ADH]] levels from [[diabetes insipidus]]
**Low [[FSH]] and [[LH]] levels from [[hypogonadotropic hypogonadism]]
**Low [[testosterone]] levels
**Low [[estrogen]] levels
 
=== Ultrasound ===
*[[Bilateral renal cysts]]
*[[Medullary cystic kidney disease]] may be present in children
*[[Hepatic fibrosis]]
*[[Renal scarring]]
 
===Echocardiogram===
*Interventricular septum hypertrophy may be present.
*[[Aortic stenosis]] may be found.
*[[Tricuspid regurgitation]] and [[pulmonic valve]] may also be involved.
 
===Other tests===
*[[Gene mapping]]
*Renal biopsy may show [[interstitial nephritis]]


== June 2006 Conference ==
== June 2006 Conference ==

Latest revision as of 18:20, 13 August 2012

Bardet-Biedl syndrome
ICD-10 Q87.8
ICD-9 759.89
OMIM 209900
DiseasesDB 7286
MeSH D020788

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Aarti Narayan, M.B.B.S [2]

Synonyms and keywords: Laurence-Moon-Biedl syndrome; Laurence-Moon-Biedl-Bardet; LMBBS; LMBS;BBS

Overview

The Bardet-Biedl syndrome is a genetic disorder characterized mainly by obesity, retinitis pigmentosa, polydactyly, mental retardation, hypogonadism, renal dysplasia and renal failure in some cases.[1]

Historical Perspective

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

Classification

Two forms have been identified:

Pathophysiology

  • Even though the detailed biochemical mechanism that leads to BBS is unclear, the syndrome is thought to result largely from a defect in basal body of ciliated cells.
  • The gene products encoded by these BBS genes (BBS1 to BBS8, called BBS proteins, are located in the basal body and cilia of the cell.[4]
  • 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 is essential for ciliogenesis and the maintenance of cilia.[5] 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 role in the ciliary function.[citation needed]
  • 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.
  • 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, causes BBS.[citation needed]
  • Genes involved include:[citation needed]

Relation to other rare genetic disorders

Differentiating Bardet-Biedl syndrome from other Diseases

  • Bardet–Biedl syndrome (BBS) and Laurence–Moon syndrome (LMS) have a similar phenotype, which includes retinal dystrophy, obesity, and hypogenitalism.
  • They are differentiated by the presence of spasticity and the absence of polydactyly in LMS.
  • The overlapping features of these cases suggested that the two disorders represented variable expression of a single condition.
  • The findings of neurological manifestations in BBS patients has prompted hypotheses that LMS and BBS are allelic.[7]

Epidemiology and Demographics

  • Bardet-Biedl syndrome has a prevalence of 1 in 125,000- 160,000 in Europe[8], whereas in Arab countries, it is about 1 in 165,000 population.[9]

Diagnosis

Symptoms

Physical Examination

Appearance of the Patient

Vital Signs

Eyes

Nose

Heart

Extremities

Neurologic

Genitourinary examination

Laboratory Findings

Ultrasound

Echocardiogram

Other tests

June 2006 Conference

  • The LMBBS Association Family Meeting for non-medical-professionals was held in Houston, Texas, June 16-17, 2006.
The conference was sponsored by a steering committee of BBS folk and parents/grandparents of children with BBS. It was directed to a lay audience.
A primary purpose of the conference was to present the latest medical research results in an accessible fashion. This included one morning of presentations by leading BBS genetic researchers Dr. Richard Lewis (Baylor Medical Center, Houston) and Dr. Nicholas Katsanis (Johns Hopkins University, Baltimore, Maryland). Several additional doctors presented accessible information on growth and weight management; kidney issues; obesity & Syndrome X; pediatric bariatric surgery; and speech pathology & therapy.
Location: Cullen Eye Institute, Baylor College of Medicine, Houston, Texas.
For additional information about the meeting, click here.

References

  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. Template:WhoNamedIt
  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. Genet. A. 132 (4): 352–60. PMID 15637713.
  4. Ansley SJ, Badano JL, Blacque OE, Hill J, Hoskins BE, Leitch CC, Kim JC, Ross AJ, Eichers ER, Teslovich TM, Mah AK, Johnsen RC, Cavender JC, Lewis RA, Leroux MR, Beales PL, Katsanis N (2003). "Basal body dysfunction is a likely cause of pleiotropic Bardet–Biedl syndrome". Nature. 425 (6958): 628–33. doi:10.1038/nature02030. PMID 14520415. Unknown parameter |month= ignored (help)
  5. 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 (13): 1630–42. doi:10.1101/gad.1194004. PMC 443524. PMID 15231740.
  6. 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.
  7. Moore SJ, Green JS, Fan Y; et al. (2005). "Clinical and genetic epidemiology of Bardet-Biedl syndrome in Newfoundland: a 22-year prospective, population-based, cohort study". American Journal of Medical Genetics. Part a. 132 (4): 352–60. doi:10.1002/ajmg.a.30406. PMC 3295827. PMID 15637713. Unknown parameter |month= ignored (help)
  8. Klein D, Ammann F (1969). "The syndrome of Laurence-Moon-Bardet-Biedl and allied diseases in Switzerland. Clinical, genetic and epidemiological studies". Journal of the Neurological Sciences. 9 (3): 479–513. PMID 5367041.
  9. Farag TI, Teebi AS (1988). "Bardet-Biedl and Laurence-Moon syndromes in a mixed Arab population". Clinical Genetics. 33 (2): 78–82. PMID 3359670. Unknown parameter |month= ignored (help)

External links

Template:Phakomatoses and other congenital malformations not elsewhere classified

da:Moon-Bardet-Biedl syndrom de:Laurence-Moon-Biedl-Bardet-Syndrom nl:Syndroom van Laurence-Moon-Bardet-Biedl fi:Bardet-Biedlin oireyhtymä


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