Bardet-Biedl syndrome
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.

# Historical Perspective
The syndrome is named after Georges Bardet and Arthur Biedl.
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.

# Classification
Two forms have been identified:
- Bardet-Biedl syndrome 1 (BBS1) has no linkage to chromosome 16
- Bardet-Biedl syndrome 2 (BBS2) is mapped to markers on chromosome 16.

# 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.
- 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. 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.
- 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.
- Genes involved include:
BBsome: BBS1, BBS2, BBS4, BBS5, BBS7, TTC8/BBS8, BBS9
chaperone: BBS6, BBS10, BBS12
Other: ARL6/BBS3, TRIM32/BBS11
- BBsome: BBS1, BBS2, BBS4, BBS5, BBS7, TTC8/BBS8, BBS9
- chaperone: BBS6, BBS10, BBS12
- Other: ARL6/BBS3, TRIM32/BBS11

## 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, MeckelGruber syndrome and some forms of retinal degeneration.

# Differentiating Bardet-Biedl syndrome from other Diseases
- BardetBiedl syndrome (BBS) and LaurenceMoon 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.

# Epidemiology and Demographics
- Bardet-Biedl syndrome has a prevalence of 1 in 125,000- 160,000 in Europe, whereas in Arab countries, it is about 1 in 165,000 population.

# 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 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
- End gaze nystagmus
- Fundoscopy:
Retinitis pigmentosa
Retinal dystrophy
- Retinitis pigmentosa
- Retinal dystrophy

### Nose
- Anosmia

### Heart
- Precordial examination:
Thrill may be present.
- Thrill may be present.
- Auscultation:
Ejection systolic murmur may be present.
Machinery murmur from patent ductus arteriosus may be present.
S3 may be heard.
- 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
- 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
- The LMBBS Association Family Meeting for non-medical-professionals was held in Houston, Texas, June 16-17, 2006.