Williams syndrome

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Williams syndrome2016-11-28T13:33:50+00:00

Williams syndrome

GENETICS, PAEDIATRICS

A rare–1:20,000 autosomal dominant multisystem neurodevelopmental disorder (OMIM:194050) characterised by:

Distinct “elfin” facies Premature wrinkling of skin, small upturned noses, shallow supraorbital ridges, depressed nasal bridge, small nose with anteverted nares, a “Cupid’s bow” upper lip, medial eyebrow flare, periorbital puffiness, short palpebral fissures, oval ears, prominent maxilla, malar hypoplasia with droopy cheeks, broad open mouths with full lips accentuated by a small chin and mandible, a long philtrum–midline of upper lip from lip margin to nose, epicanthal folds, characteristic dental defects–carious peg teeth, absence of teeth, defective tooth enamel, stellate patterning of irises

Congenital heart disease Stenoses of great vessels–supravalvular aortic stenosis, multiple peripheral pulmonary arterial stenoses, septal defects

Other findings Angina, stomach pains, constipation, hernias, irritability, infantile hypercalcemia, hoarse voice, delayed mental and physical development, syncope, onychodysplasia, feeding difficulties, failure to thrive, poor fine motor skills, statural deficiency. Bony abnormalities include osteosclerosis induced by hypercalcemia, pectus excavatum, inwardly bent small finger–clinodactyly, inwardly pointed great toe, nephrosclerosis, occasionally sudden death

• Despite their low IQs of ± 50, Williams disease patients often have enhanced verbal abilities, rich vocabularies, are expressive, may be highly skilled musicians and singers, extremely sociable, and adept at vacuous “cocktail party” chatter

Some believe that Williams syndrome patients were the living inspiration for folk legends of elves, pixies, and fairies given their characteristic facial features (above).

Molecular pathology Williams syndrome is caused by hemizygous deletion of 1.5 to 1.8 Mb on chromosome 7q11.23, which contains approximately 28 genes.

Defects seen in Williams syndrome include: 

• Deletion of ELN, which encodes elastin, a major structural protein of tissues such as aorta and nuchal ligament 

• Deletion of RFC2, which encodes a subunit of a protein complex responsible for the elongation of primed DNA templates by DNA polymerase delta and epsilon. The RFC2 product is responsible for binding ATP and may help promote cell survival

• Heterozygosity of LIMK1, which encodes a LIM domain serine/threonine kinase that regulates actin polymerisation. 

• Deletion of CLDN4, which encodes claudin 4, an integral membrane protein components of the epithelial cell tight junctions

• Haploinsufficiency of GTF2I, which encodes a phosphoprotein that regulates yranscription and may cause cardiovascular and musculo-skeletal abnormalities observed in the disease.

*The loss of multiple adjacent genes typically results in a so-called contiguous gene syndrome

Synonyms Chromosome 7q11.23 deficiency syndrome, elfin facies syndrome, supravalvar aortic stenosis syndrome, Williams-Beuren syndrome 

References http://www.uniprot.org/uniprot/P53667

http://www.omim.org/entry/194050

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