Laboratory for Molecular Diagnostics
Center for Nephrology and Metabolic Disorders

Bardet-Biedl syndrome

Although Bardet-Biedl syndrome is a genetically heterogeneous autosomal recessive disorder, there are striking similarities: pigmentary retinopathy, distal limb abnormalities, renal abnormalities, obesity, hypogenitalism in men, and mental retardation.

Historical Aspects

In 1866, Laurence and Moon were the first to publish a case of an obese, visually impaired girl with intellectual disabilities. In the 1920s, Bardet and Biedl independently added the symptoms of polydactyly and hypogenitalism and defined our current understanding of the syndrome.[Error: Macro 'ref' doesn't exist]

Epidemiology

Bardet-Biedl syndrome is rare, but in some geographically isolated regions, such as Newfoundland and Kuwait, the prevalence is higher (1:13,500 to 1:17,500).

Clinical Findings

The primary definition of symptoms typical of Bardet-Biedl syndrome includes obesity, visual impairment, intellectual disability, polydactyly, and hypogenitalism. As more clinical data accumulated and molecular genetic diagnostic became available, the variation among these symptoms' severity became apparent, which wreaked classification of clinical signs into primary and secondary.

Limb Abnormatlities

Limb abnormatlities focus on fingers. Moren than two third of patients have at least one additional finger at birth, which is usually fully boned and located on the lateral border of the hand or foot. This post-axial polydactyly is present on all four limbs or on feet only in about 20%. In 8% hands are the only affected site. Occurring in about half of the patients, brachydactyly is also common. Syndactyly usually occurring between the second and third fingers can also bee present in about 8% of cases.

Eye Anomalies

Rod-cone dystrophy also termed atypical retinitis pigmentosa amounts to eye anomalies. This finding is very common and is present in almost all patients whereas other features as strabism, astigmatism, cataracts, colour blindness, macular oedema and degeneration, and optic atrophy can be found in less than 8% of patients. Visual impairment becomes obvious at about 8 years of age and is first noted by night blindness. The mean age at which patients become blind is 15,5 years (range 8-43 years).

Height and Weight

Height and weight is typically altered. Although only male patients are slightly smaller, both sexes are overweight 79% and even obese 50%.

Renal Tract Abnormalities

With the possibility to perform more subtle renal investigation, renal tract abnormalities became a key feature of the disease. About half of the patients, who have underwent radiological investigation, show urinary tract malformations, including parenchymal cysts/communicating calyceal cysts (10%), calyceal clubbing and blunting (10%), fetal lobulation (12%), scarring (12%), unilateral agenesis (4%), dysplastic kidneys (5%), renal calculi (2%), and vesicoureteric reflux (9%). In about 10% this damage causes renal failure and end stage renal disease (5%).

Hypogonadism

Most male patients show hypogonadism while most females experience irregular mentruation cycles.

Diagnosis

The diagnosis is often delayed because often medical awareness of this rare disease is lacking and symptoms develop so slowly.

Early eye examination revealing rod-cone dystrophy spurs the diagnosis. For the clinical diagnosis to be settled, it is necessary to meet the clinical diagnostic requirements which is the presence of four primary or three primary and two secondary features. Molecular genetic analysis when possible and successful allows to make the definite diagnosis in oligosymptomatic cases and identify heterozygous carriers.

Primary features

Most important to the clinical diagnosis are the primary features, four of which are required for the clinical diagnosis to be definite: rod-cone dystrophy, polydactyly, obesity, learning disabilities, hypogonadism in males, renal anomalies.

Secondary features

If only three primary feature are present, two more secondary features can help to definitely make the diagnosis: speech disorder/delay, strabismus/cataracts/astigmatism, brachydactyly/syndactyly, developmental delay, polyuria/polydipsia (nephrogenic diabetes insipidus), ataxia/poor coordination/imbalance, mild spasticity (especially lower limbs), diabetes mellitus, dental crowding/ hypodontia/small roots/high arched palate, left ventricular hypertrophy/congenital heart disease, hepatic fibrosis.

Symptoms

Syndactyly
In Bardet-Biedl syndrome syndactyly is accompanied by renal symptoms.

Systematic

Interstitial kidney disease
Alström syndrome
Autosomal dominant tubulointerstitial kidney disease (ADTKD)
Bardet-Biedl syndrome
Bardet-Biedl syndrome 01
ARL6
BBS1
CCDC28B
TMEM67
Bardet-Biedl syndrome 02
BBS2
Bardet-Biedl syndrome 03
ARL6
Bardet-Biedl syndrome 04
BBS4
Bardet-Biedl syndrome 05
BBS5
Bardet-Biedl syndrome 06
MKKS
Bardet-Biedl syndrome 07
BBS7
Bardet-Biedl syndrome 08
TTC8
Bardet-Biedl syndrome 09
BBS9
Bardet-Biedl syndrome 10
BBS10
Bardet-Biedl syndrome 11
TRIM32
Bardet-Biedl syndrome 12
BBS12
Bardet-Biedl syndrome 13
MKS1
Bardet-Biedl syndrome 14
CEP290
Bardet-Biedl syndrome 15
WDPCP
Bardet-Biedl syndrome 16
SDCCAG8
Bardet-Biedl syndrome 17
LZTFL1
Bardet-Biedl syndrome 18
BBIP1
Bardet-Biedl syndrome 19
IFT27
Bardet-Biedl syndrome 20
IFT74
Hyperuricemic nephropathy
Karyomegalic interstitial nephritis
Medullary cystic disease complex

References:

1.

Beales PL et al. (1999) New criteria for improved diagnosis of Bardet-Biedl syndrome: results of a population survey.

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2.

Beales PL et al. (2000) Renal cancer and malformations in relatives of patients with Bardet-Biedl syndrome.

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3.

Tobin JL et al. (2007) Bardet-Biedl syndrome: beyond the cilium.

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4.

Orphanet article

Orphanet ID 110 [^]
5.

Wikipedia article

Wikipedia EN (Bardet–Biedl_syndrome) [^]
Update: May 9, 2019