Williams Syndrome

CLINICAL CHARACTERISTICS

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

DIAGNOSIS/TESTING: The diagnosis of WS is established by identification of a heterozygous 1.5- to 1.8-Mb deletion of the Williams-Beuren syndrome critical region (WBSCR) on chromosome 7q11.23.

MANAGEMENT

Infants with feeding issues may benefit from feeding therapy. Early intervention programs, special education programs, and vocational training address developmental disabilities; programs include speech-language, physical, occupational, feeding, and sensory integration therapies as well as hippotherapy; phonics methods are recommended to teach reading. Psychological and psychiatric evaluation and treatment provide individualized behavioral counseling and medications, especially for attention-deficit/hyperactivity disorder and anxiety. Surgery may be required for supravalvar aortic or pulmonary artery stenosis, mitral valve insufficiency, and/or renal artery stenosis. Anesthesia consultation and electrocardiogram is recommended prior to sedation and surgical procedures. Orthodontic referral should be considered for malocclusion. Constipation should be aggressively managed at all ages. The lower urinary tract should be evaluated in those with febrile urinary tract infections; refer to a nephrologist for management of nephrocalcinosis, persistent hypercalcemia, and/or hypercalciuria. Range of motion exercises are recommended to prevent or ameliorate joint contractures. Treatment of hypercalcemia may include diet modification, oral corticosteroids, and/or intravenous pamidronate. Early puberty may be treated with a gonadotropin-releasing hormone agonist. Treatment of hypertension, sleep disorders, ocular manifestations, recurrent otitis media, hearing loss, dental issues, hypothyroidism, and insulin resistance does not differ from that in the general population. : 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. Medical evaluation, vision screening, hearing evaluation, measurement of blood pressure in both arms, calcium-to-creatinine ratio in spot urine, and urinalysis should be performed annually. Additional periodic evaluations for all individuals include: measurement of serum concentration of calcium every two years; cardiology evaluation for elastin arteriopathy at least annually until age five years and every two to three years thereafter; and renal and bladder ultrasound examination every ten years. Oral glucose tolerance tests in adults should start at age 20 years. Multivitamins for children, because all pediatric multivitamin preparations contain vitamin D.

GENETIC COUNSELING

WS is an autosomal dominant disorder. Most individuals diagnosed with WS have the disorder as the result of a 1.5- to 1.8-Mb 7q11.23 deletion; rarely, an individual with WS has an affected parent. Recommendations for the parents of a proband with WS include obtaining a medical history to determine if signs or symptoms of WS are present. In the absence of clinical findings of WS in the parents, testing of the parents for the 7q11.23 deletion identified in the proband is not warranted. Each child of an individual with WS has a 50% chance of inheriting the 7q11.23 deletion and being affected. Once the WS-causing 1.5- to 1.8-Mb 7q11.23 deletion has been identified in an affected family member, prenatal and preimplantation genetic testing are possible.