WAARDENBURG SYNDROMES
 
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WAARDENBURG SYNDROMES

 

DEFINITION:

A disorder of unknown etiology characterized by pigmentation changes, deafness, and midface anomalies.

EPIDEMIOLOGY:

  • incidence: 1-2/20,000
  • age of onset:
    • newborn (dysmorphic features)
  • risk factors:
    • familial - autosomal dominant (all 3 types with 85% penetrance in Type 1)
      • chrom.#: 2q35 (Type 1)
      • gene: paired box homeotic gene-3
    • M = F
    • older paternal age in de novo mutations

PATHOGENESIS:

1. Background

  • etiology unknown
  • first described in 1951 by Waardenburg in a group of congenitally deaf children

2. Genetic Defect

  • genetic defect -> impaired paired box homeotic gene-3 -> ? defect in migration of neural crest cells -> clinical manifestations:

1. Pigmentary Changes

1. Ocular

  • heterochromia irides
    • total or partial (may be restricted to a single segment of one eye)
  • isochromia
    • pale or bright blue irides with hypoplasic iridic stroma
  • albinotic fundi
    • mottled peripheral pigmentation of retina

2. Hair/Cutaneous

1. Hair
  • poliosis (white forelock) may be present at birth, disappear then reappear
  • may have other patches of white hair
  • premature greying of hair, eyelashes, and eyebrows (as early as 7 years of age)
2. Cutaneous
  • areas of vitiligo in 15% of cases on arms and face

2. Auditory Changes

  • atrophic changes in the spiral ganglion and nerve (Organ of Corti) may impair vestibular function
  • unilateral or bilateral sensorineural hearing loss or deafness
  • high association of deafness with other phenotypic characteristics

3. Midface Anomalies

  • dystopia canthorum
    • lateral displacement of the inner canthi
  • broad nasal bridge with lack of frontonasal bridge, and bulbous nose with hypoplastic alae nasi
  • synophrys (confluent eyebrows)

CLINICAL FEATURES:

1. Major Features

  • dystopia canthorum (80-99%)
  • broad nasal bridge with lack of frontonasal bridge, and bulbous nose with hypoplastic alae nasi (80%)
  • synophrys (50%)
  • heterochromia irides (25%)
  • poliosis (20-40%)
  • congenital deafness (20%)

2. Type I (dystopia canthorum present)

  • all features above
  • deafness in 25%

3. Type II (dystopia canthorum absent)

  • all features above
  • deafness in 50%
  • unilateral ptosis and Marcus Gumm phenomenon

4. Type III (Klein-Waardenburg limb anomalies)

  • all features above
  • bilateral upper limb defects
    • hypoplasia, contractures, carpal fusion, syndactyly
    • upper limb-pectoral girdle arthromyodysplasia
  • blepharophimosis

5. Other Anomalies Observed

  • Hirshsprung megacolon or atretic gastrointestinal disorders (I and II)
  • congenital heart disease (VSD)

INVESTIGATIONS:

1. Imaging Studies

  • x-rays of upper limbs

2. Ophthalmologic

  • ocular defects

3. Auditory

  • sensorineural hearing loss or deafness

MANAGEMENT:

1. Supportive

  • regular ophthalmologic and auditory assessments
  • genetic counselling
  • prognosis - normal life span with no mental retardation

 

Pediatric Database - WAARDENBURG SYNDROMES

 

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