Williams Syndrome

Excerpt

Clinical characteristics: Williams syndrome (WS) is characterized by cardiovascular disease (elastin arteriopathy, peripheral pulmonary stenosis, supravalvar aortic stenosis, hypertension), distinctive facies, connective tissue abnormalities, intellectual disability (usually mild), a specific cognitive profile, unique personality characteristics, growth abnormalities, and endocrine abnormalities (hypercalcemia, hypercalciuria, hypothyroidism, and early puberty). Feeding difficulties often lead to poor weight gain in infancy. Hypotonia and hyperextensible joints can result in delayed attainment of motor milestones.

Diagnosis/testing: Clinical diagnostic criteria are available for Williams syndrome; however, the diagnosis requires detection of a recurrent 7q11.23 contiguous gene deletion of the Williams-Beuren syndrome critical region (WBSCR) that encompasses the elastin gene (ELN). This contiguous gene deletion can be detected using fluorescent in situ hybridization (FISH) and/or deletion/duplication testing.

Management: Treatment of manifestations: Early intervention programs, special education programs, and vocational training address developmental disabilities; programs include speech/language, physical, occupational, feeding, and sensory integration therapies. Psychological and psychiatric evaluation and treatment provide individualized behavioral counseling and medications, especially for attention deficit disorder and anxiety. Surgery may be required for supravalvar aortic or pulmonary artery stenosis, mitral valve insufficiency, and/or renal artery stenosis. Treatment of hypercalcemia may include diet modification, oral corticosteroids, and/or intravenous pamidronate. Refer to a nephrologist for management of nephrocalcinosis, persistent hypercalcemia, and/or hypercalciuria. Treatment of hypertension, hyperopia, and recurrent otitis media does not differ from that in the general population. Orthodontic referral should be considered for malocclusion. Infants with feeding problems may benefit from feeding therapy. Constipation should be aggressively managed at all ages. Early puberty may be treated with a gonadotropin-releasing hormone agonist.

Prevention of secondary complications: Range of motion exercises to prevent or ameliorate joint contractures; anesthesia consultation and electrocardiogram prior to sedation and surgical procedures.

Surveillance: Annual medical evaluation, vision screening, hearing evaluation, measurement of blood pressure in both arms, calcium/creatinine ratio in spot urine, and urinalysis. Children younger than age two years should have serum calcium studies every four to six months. Thyroid function should be checked yearly until age three years and every two years thereafter. Additional periodic evaluations for all individuals include: measurement of serum concentration of calcium every two years; cardiology evaluation for elastin arteriopathy at least annually for the first five years and every two to three years thereafter for life; and renal and bladder ultrasound examination every ten years. Additional periodic evaluations during adulthood include: oral glucose tolerance; cardiac evaluation for mitral valve prolapse, aortic insufficiency, hypertension, long QT interval, and arterial stenoses; and ophthalmologic evaluation for cataracts.

Agents/circumstances to avoid: Multivitamins for children because all pediatric multivitamin preparations contain vitamin D.

Genetic counseling: Williams syndrome is transmitted in an autosomal dominant manner. Most cases are de novo occurrences, but occasionally, parent-to-child transmission is observed. Prenatal testing is possible but is rarely used because most cases occur in a single family member only, and no prenatal indicators exist for low-risk pregnancies.