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Bardet-Biedel syndrome
Clinical feature:
Definition: Although Bardet-Biedel 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.
History: 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.
Epidemiology: Bardet-Biedel 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 picture: 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 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.
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 strabismus, 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 is typically altered. Although only male patients are slightly smaller, both sexes are overweight 79% and even obese 50%.
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%).
Most male patients show hypogonadism while most females experience irregular mentruation cycles.
Diagnostics:
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.
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.
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.
Differential: It might pose a problem distinguishing between Bardet-Biedl syndrome and autosomal recessive polycystic kidney disease in very your patients when most of the features of BBS have not yet developed. In these cases molecular genetic analysis can be the only reliable diagnostic method.
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There is a large and heterogeneous group of hereditary diseases (CAKUT) that cause similar urogenital tract malformations.
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If impaired hearing, renal failure, and ocular abnormalities dominate the clinical picture an Alport syndrome might be considered, in which however the first urinary finding is glomerular hematuria, hearing loss is sensorineural, and ocular findings do not include retinitis pigmentosa.
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