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At a glance

A syndrome characterized by the presence of peculiar facial features such as broad forehead, short nose and full cheeks, giving an appearance of an “elfin (a small and delicate person in the enchanted world, typically with an attractively mischievous and/or strange charm).” Other clinical features include mild to moderate intellectual disability, very pleasant personality and ability to interact readily with strangers. It is associated with infantile hypercalcemia, cardiac defect in 80% (supravalvular aortic stenosis and peripheral pulmonary artery stenoses), and a high incidence of sudden death. Recent research has shown that the QTc interval in Williams Syndrome (WS) patients is significantly prolonged and may be associated with the sudden death.

Synonyms

Williams-Beuren Syndrome; Williams-Barratt Syndrome; Fanconi-Schlesinger Syndrome; Elfin Facies Syndrome; Hypercalcemia-Peculiar Facies-Supravalvular Aortic Stenosis Syndrome; Early Hypercalcemia Elfin Facies Syndrome; Beuren Syndrome; WBS.

History

This medical entity was described by J. C. P. Williams, a New Zealand cardiologist, in 1961.

Incidence

It affects 1:7,000 to 20,000 live births in the general population. The life expectancy is shorter than reported in the normal population due to the heart disease.

Genetic inheritance

It is inherited as an autosomal dominant with some familial cases, but most seem to be sporadic. It is believed a Contiguous Gene Syndrome. It has been linked to chromosome 7 (7q11.23).

Pathophysiology

Because of the transient hypercalcemia occurring early during infancy, it has been proposed that Williams Syndrome may be caused by an abnormal metabolism of calcium and vitamin D, but this remains to be proven. Mutations (deletions) in the elastin gene (ELM) are responsible, at least in part, for the disorder. The gene for LIM-kinase-1 is also involved in the pathogenesis, and haploinsufficiency of the RFC2 gene has also been postulated as a factor.

Diagnosis

The diagnosis is a clinical one based on the characteristic facial features giving the appearance of an elfin. It is associated with mild to moderate mental retardation, cardiovascular disease, and neonatal hypercalcemia. The diagnosis is established by chromosomal studies (molecular biology). Radiographs may show increased calcification of skull base, periorbital area, and vertebral plates. Angiographic studies evaluate extent and type of vascular lesions.

Clinical aspects

The main features of the characteristic facies are epicanthal folds, flat nasal bridge, anteverted nostrils, blue stellate iris, and mandibular hypoplasia associated with dental anomalies and a tendency to keep mouth open. Patients also have a typical hoarse voice. Neonatal hypercalcemia is common and can lead to nephrocalcinosis. The main cardiovascular anomaly is supravalvular aortic stenosis, but other anomalies can be present. Sudden death is frequent in patients with coronary artery stenosis or severe biventricular outflow tract obstruction and is a result of myocardial ischemia, decreased cardiac output, and ...

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