A syndrome characterized by peculiar elfin facies
associated with infantile hypercalcemia, cardiac defect and mild mental
retardation. High incidence of sudden death.
Williams-Beuren Syndrome; Williams-Barratt Syndrome;
Fanconi-Schlesinger Syndrome; Elfin Facies Syndrome; Hypercalcemia-Peculiar
Facies-Supravalvular Aortic Stenosis Syndrome.
This medical entity was described by J.C.P. Williams, a New Zealand
1:20,000-50,000 live births.
Autosomal dominant with some familial cases,
but most seem to be sporadic. Contiguous gene syndrome. Link to chromosome 7
Because of the transient hypercalcemia occurring
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.
The diagnosis is a clinical one based on the
characteristic elfin facies associated with mental retardation,
cardiovascular problem, and neonatal hypercalcemia. 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.
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 arrhythmia. The overall
incidence of sudden death over a 30-year period is reported to be 3%. Patients usually
have a friendly personality and normal language skills despite their mental retardation
(IQ 40 to 80). During infancy, they may present with hypotonia, which may remain the same
or convert to hypertonia at an older age. As the patients grow older, they may develop
hypertension, progressive joint limitations, recurrent urinary tract infections, obesity,
diverticulosis, and cholelithiasis. Other features include hypoplastic nails,
clinodactyly, hallux valgus, pectus excavatum, umbilical hernia, and a small penis.
Baseline ECG and echocardiogram
should be obtained before surgery and exercise tolerance evaluated, as well
as signs of cardiac insufficiency. In infants, hypercalcemia needs to be
investigated, because it is more prevalent among this age group. Also, young
children present with a feeding problem and frequent vomiting, thus
aspiration prophylaxis may be warranted. Evaluate blood chemistries,
calcemia (prevention of nephrocalcinosis and deafness), blood group,
hemoglobin, and coagulation.
Tracheal intubation might be problematic
because of the hypoplastic mandible and dental anomalies. The main problem
associated with anesthesia is the aortic stenosis; those patients with
aortic stenosis should be ...