Williams Syndrome: Introduction

Williams Syndrome (WS) is a rare genetic disorder characterized by developmental delays, distinctive facial features, cardiovascular abnormalities, and a unique cognitive profile. It is caused by a deletion of approximately 26-28 genes on chromosome 7q11.23. The estimated prevalence is 1 in 7,500 to 1 in 20,000 live births.

Key points:

• Autosomal dominant inheritance pattern
• Sporadic occurrence in most cases (de novo deletion)
• Affects multiple body systems
• Requires multidisciplinary management

Clinical Features of Williams Syndrome

Facial Characteristics:

• Broad forehead
• Bitemporal narrowing
• Periorbital fullness
• Stellate iris pattern
• Short, upturned nose with anteverted nares
• Long philtrum
• Full lips and wide mouth
• Small, widely spaced teeth
• Micrognathia (small chin)

Cardiovascular Abnormalities:

• Supravalvular aortic stenosis (SVAS) - most common (75% of cases)
• Peripheral pulmonary stenosis
• Mitral valve prolapse
• Hypertension

Neurodevelopmental Profile:

• Mild to moderate intellectual disability (average IQ: 50-60)
• Relative strength in verbal abilities and auditory memory
• Weakness in visuospatial construction
• Hypersociability and excessive friendliness
• Anxiety disorders, particularly specific phobias
• Attention Deficit Hyperactivity Disorder (ADHD)

Other Features:

• Growth delay and short stature
• Hypercalcemia (15% of cases)
• Hypothyroidism
• Gastrointestinal issues (feeding difficulties, constipation)
• Joint laxity and muscle hypotonia
• Sensorineural hearing loss
• Strabismus and hyperopia
• Dental abnormalities

Diagnosis of Williams Syndrome

Clinical Diagnosis:

Suspicion based on characteristic facial features, cardiovascular abnormalities, and developmental delay.

Genetic Testing:

• Fluorescence in situ hybridization (FISH) - detects 7q11.23 deletion
• Multiplex ligation-dependent probe amplification (MLPA)
• Chromosomal microarray analysis (CMA)

Additional Evaluations:

• Echocardiogram and cardiac evaluation
• Developmental and cognitive assessments
• Ophthalmological examination
• Audiological evaluation
• Endocrine evaluation (calcium, thyroid function)
• Renal ultrasound
• Blood pressure monitoring

Management of Williams Syndrome

Management of Williams Syndrome requires a multidisciplinary approach:

Cardiovascular Care:

• Regular cardiac evaluations
• Surgical intervention for severe SVAS or other defects
• Hypertension management

Developmental Support:

• Early intervention programs
• Special education services
• Speech and language therapy
• Occupational therapy
• Physical therapy

Behavioral and Mental Health:

• Psychological support for anxiety and ADHD
• Social skills training
• Behavioral interventions

Endocrine Management:

• Monitoring and treatment of hypercalcemia
• Thyroid function tests and management

Gastrointestinal Care:

• Dietary modifications for feeding difficulties
• Management of constipation

Other Considerations:

• Regular ophthalmological and audiological check-ups
• Dental care and orthodontic evaluation
• Genetic counseling for family planning