What is the management approach for Williams-Beuren syndrome?

Management of Williams-Beuren Syndrome

Patients with Williams-Beuren syndrome require lifelong annual cardiovascular follow-up at a specialized Adult Congenital Heart Disease (ACHD) center, combined with mandatory long-term psychosocial assessment including evaluation for legal guardianship needs. 1

Cardiovascular Management

Initial Evaluation and Monitoring

• Perform comprehensive cardiac assessment at diagnosis including three-limb blood pressure measurements (both arms and one leg), echocardiogram with Doppler flow studies, and evaluation for supravalvular aortic stenosis (SVAS), which occurs in approximately 80% of patients 1, 2
• Screen for coronary artery involvement as ostial or diffuse coronary stenosis is a frequent occurrence and represents a major cause of sudden cardiac death 1, 2
• Obtain cardiovascular MRI or CT scan to completely evaluate the thoracic aorta, branch vessels, pulmonary arteries, and renal arteries, as arterial stenosis can occur at any level 1
• Monitor blood pressure manually at every visit using both arms at the end of the visit to minimize anxiety, as hypertension occurs in 50% of patients and may present at any age 1, 3

Surgical Indications for SVAS

Operative intervention is indicated for:

• Mean gradient >50 mmHg or peak instantaneous Doppler gradient >70 mmHg with symptoms (angina, dyspnea, syncope) 1
• Lesser degrees of obstruction with any of the following: symptoms, LV hypertrophy, desire for increased exercise or planned pregnancy, or LV systolic dysfunction 1

Hypertension Management

• Initiate calcium channel blockers as first-line therapy for hypertension, as they successfully control blood pressure in most WBS patients and ameliorate vascular stiffness 1, 3
• Refer to cardiology or nephrology when blood pressure exceeds the 90th percentile for age and height 1
• Perform arteriography selectively if hypertension is refractory to medical management, though interventional treatment of renal artery stenosis has shown limited success (effective in only 20% of cases) 3

Metabolic and Nutritional Management

Hypercalcemia Surveillance

• Check serum calcium every 4-6 months until age 2 years, then every 2 years thereafter, and whenever hypercalcemia is clinically suspected 1
• Treat symptomatic hypercalcemia (presenting with irritability, vomiting, constipation, muscle cramps) with low-calcium diet and increased water intake under medical supervision 1
• Maintain reference daily calcium intake in normocalcemic children; do not restrict calcium without medical supervision 1

Gastrointestinal Management

• Aggressively treat chronic constipation with increased water and fiber, followed by osmotic laxatives, to prevent complications including rectal prolapse, hemorrhoids, and intestinal perforation 1
• Maintain high index of suspicion for diverticulitis in adolescents and adults, as it occurs at unusually young ages in WBS 1, 4
• Evaluate abdominal pain systematically for gastroesophageal reflux, hiatal hernia, constipation, cholecystitis, diverticular disease, and discrete arterial stenosis causing ischemia 1

Genitourinary Management

• Assess kidney function at diagnosis with serum urea nitrogen, creatinine, and urinalysis 1
• Screen for urinary tract malformations (present in 10%) and bladder diverticula (present in 50%) 1
• Anticipate delayed continence: daytime continence typically achieved by age 4 years, but nocturnal enuresis persists in 50% at age 10 years and 13.5% of teenagers 1

Neurodevelopmental and Psychosocial Management

Early Intervention

• Refer immediately to early intervention programs for physical, occupational, and speech therapy evaluation, as developmental milestones are universally delayed 1
• Consider hippotherapy referral to address balance problems using equine movement during therapy 1
• Implement nightly stretching range-of-motion exercises to prevent joint contractures that develop in older children and adults despite early joint laxity 1

Cognitive and Behavioral Support

• Recognize that 75% will have intellectual disability with a unique cognitive profile characterized by visuospatial deficits contrasting with relatively preserved language 1, 5
• Do not overestimate executive functioning based on verbal and social skills, as these patients demonstrate hypersocial behavior that masks cognitive limitations 1, 5
• Establish legal guardianship when appropriate through formal competency assessment for self-care 1

Perioperative Risk Management

Patients with WBS face markedly elevated risk of sudden cardiac death during sedation and anesthesia, particularly those with biventricular outflow tract obstruction, with mortality rate of 6% for cardiac surgery or catheterization 1, 2. Prioritize non-invasive cardiovascular assessment whenever possible and ensure procedures are performed at specialized centers with WBS expertise 6.

Genetic Counseling and Family Screening

• Screen all available relatives for hypertension, coronary disease, and stroke, as supravalvular aortic stenosis (whether associated with WBS or nonsyndromic) has strong likelihood of being inherited 1
• Counsel against pregnancy in patients with significant SVAS obstruction, coronary involvement, or aortic disease 1

Critical Pitfalls to Avoid

• Never restrict calcium without medical supervision in normocalcemic patients, as appropriate calcium intake is essential 1
• Do not rely on symptom reporting alone for cardiovascular assessment, as 95% of hypertensive patients are asymptomatic 3
• Avoid underestimating surgical risk during any procedure requiring sedation or anesthesia due to coronary artery abnormalities 1, 2
• Do not assume interventional treatment of renal artery stenosis will control hypertension, as it remains ineffective in 80% of cases; medical management with calcium channel blockers is more reliable 3