WILLIAMS SYNDROME
 
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WILLIAMS SYNDROME

 

DEFINITION:

A developmental disorder classically characterized by the triad of typical facial features, infantile hypercalcemia, and supravalvular aortic stenosis.

EPIDEMIOLOGY:

  • incidence: 1/10,000 - 1/50,000
  • age of onset:
    • newborn -> early childhood
  • risk factors:
    • familial - autosomal dominant (but most cases represent de novo mutations)
      • chrom.#: 1q11.23
      • gene: elastin
    • M = F

PATHOGENESIS:

1. Background

  • the recognition of Williams Syndrome (WS) arose from the identification of two groups of patients with idiopathic infantile hypercalcemia in the 1950's: mild and severe forms. Those with the severe form were noted to have additional features including "elfin" facies, persistent mental deficiency, and a significant heart murmer (supravalvular aortic stenosis)
  • syndrome first described by Williams et al. in 1961
  • a diagnostic scoring system was developed by Preus - Clinical Genetics 25:422 (1984)
  • review of WS in the American Journal of Medical Genetics Supplement 6: 84-131 (1990)
  • hemizygosity at the elastin gene locus in patients with WS was first reported by Ewart et al. - Nature Genetics 5: 11-16 (1993)

2. Genetic Defect

  • genetic defect -> complete deletion within one elastin gene allele -> widespread abnormal connective tissue within various organs and systems
  • the autosomal dominant form of supravalvular aortic stenosis is also caused by variable incomplete deletions within the elastin gene but only the connective tissue within the vascular system is affected (as opposed to in WS where there appears to be a complete deletion within and adjacent to the elastin gene which results in widespread involvement of the connective tissue within many systems and organs)

CLINICAL FEATURES:

1. Neurologic/Behavioural Manifestations

1. Motor

  • multiple developmental motor disabilities affecting strength balance, coordination, and motor planning

2. Speech and Language

  • delayed expressive and receptive language skills
  • "cocktail party speech", hyperverbal

3. Behavioural

  • hyperreactivity
    • emotional insecurity - anticipatory anxiety
    • attention deficit hyperactivity disorder
    • short attention span with distractability
    • social - gregarious, loquacious, enthusiastic

4. Cognition

  • mean IQ of 85 with range from 20-106
  • cognitive dysfunction ranging from mental retardation to learning disabilities
  • better reading than math ability

2. Facial Manifestations

  • the characteristic "elfin" facies may not be evident until 1.5- 2 years of age
  • features
    • short anteverted nares
    • long, smooth philtrum
    • full, pouting cheeks
    • flat, malar eminences
    • broad maxilla and small mandible
    • full lips with full nasal tip
    • wide mouth
    • dental malocclusion
    • prominent ears
    • long ears

3. Cardiovascular Manifestations

1. Congenital Heart Disease

  • supravalvular aortic stenosis
  • pulmonic valvular stenosis
  • peripheral pulmonary artery stenosis
  • aortic hypoplasia
  • ASD, VSD
  • renal artery stenosis +/- hypertension

4. Gastrointestinal Manifestations

  • cholelithiasis
  • chronic constipation
  • diverticulosis
  • feeding problems with vomiting
  • inguinal hernia
  • obesity

5. Genitourinary Manifestations

  • bladder diverticula
  • Fanconi's Syndrome
  • urethral stenosis
  • vesicoureteral reflux (due to hypercalcemia)

6. Musculoskeletal Manifestations

  • low birth weight
  • growth retardation through the first 4 years followed by catch-up but ultimately achieve short adult stature
  • initial joint laxity followed by joint contractures

7. Ophthalmologic Manifestations

  • stellate patterning of the iris
  • strabismus

8. Cutaneous Manifestations

  • sacral creases (unilateral and bilateral)
  • hemangiomas

INVESTIGATIONS:

1. Serum

  • elevated calcium

2. Imaging Studies

1. Skeletal X-rays

  • radioulnar synostosis

2. Echocardiogram

  • congenital heart defects

MANAGEMENT:

1. Supportive

  • multidisciplinary approach
    • Paediatrics, Cardiology, Neurology, Orthopedics, Urology, Gastrology, Ophthalmology, Dentistry, Psychology, PT, OT
    • genetic counselling
    • individualized education programmes
    • speech therapy

2. Medical

1. Hypercalcemia

  • elimination of vitamin D and calcium from the diet

INTERNET LINKS:

Comprehensive Williams Syndrome Home Page
Williams Syndrome Association
Williams Syndrome Monthly Medline Alert

 

Pediatric Database - WILLIAMS SYNDROME

 

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