Williams Syndrome

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 cardiologist.

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 (7q11.23).

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 managed in such a fashion as to limit myocardial oxygen demand. In older patients, because of the progressive joint limitation, positioning might be more difficult and the anesthetist must ensure an adequate padding.

Even though this syndrome has not been formally associated with malignant hyperthermia, the two diseases have similar genetic defects. There are two case reports in the literature of abnormally elevated creatinine kinase after general anesthesia in one patient and masseter spasm in the other patient; consequently, it must be kept in mind that these patients might be more susceptible to malignant hyperthermia than the general population. Succinylcholine is best avoided. Nondepolarizing muscle relaxants should be used only after the airway is secure. Prophylactic antibiotics in cases of cardiopathy.

Noonan Syndrome: A rare genetic disorder characterized by a wide spectrum of symptoms and physical features that vary greatly in range and severity. In many affected individuals, associated abnormalities include a distinctive facial appearance; a broad or webbed neck; a low hairline in the back of the head; and short stature. Pulmonary valvular stenosis is often present.

Idiopathic Infantile Hypercalcemia: Characterized by the idiopathic elevation of blood calcium levels in a newborn. Anorexia, irritability, confusion, weakness, easy fatigability, and/or abdominal and muscle pain are reported. Some studies in the medical literature question whether idiopathic infantile hypercalcemia is a separate disorder from Williams syndrome or simply a variant of the same disease. However, infants with this form of the disease do not have the characteristic facial features or heart defects that are associated with Williams syndrome.