Waardenburg syndrome

Last revised by Frank Gaillard on 14 May 2024

Waardenburg syndrome is a rare neurocristopathy, with congenital pigmentary disorder secondary to an abnormal distribution of neural crest-derived melanocytes during embryogenesis resulting in patchy areas of depigmentation. It is considered in the investigation of congenital sensorineural deafness.

Estimated prevalence of 1:42000 live births, with equal gender prevalence. Present in 2-5% of patients with congenital deafness 3.

The major manifestations of this syndrome include:

  • pigmentation changes

    • hair: premature graying, characteristic white forelock (poliosis)

    • eyes: eyes with two different color irises (complete heterochromia irides), eyes with one iris having different colors (sectoral heterochromia irides), very pale or striking blue eyes

    • skin: patchy hypopigmented lesions

  • telecanthus (lateral displacement of the inner canthi of the eyes) secondary to a prominent nasal root.

  • varying degrees of congenital sensorineural deafness (occurs in one in five patients)

  • neurologic manifestations

    • peripheral neuropathy

    • cerebellar ataxia

    • intellectual disability

Findings can also include:

  • upper limb contractures (type III, Klein-Waardenburg syndrome)

  • Hirschsprung's disease (type IV, Waardenburg-Shah syndrome)

  • anosmia due to arhinencephaly 7

  • parotid and lacrimal gland hypoplasia 7

Waardenburg syndrome is due to an abnormal distribution of neural crest-derived melanocytes during embryogenesis. There are at least four subtypes, with varying physical manifestations and genetic profiles.

It is usually inherited in an autosomal dominant pattern, involving PAX3 or MITF 3. However, some cases can have an autosomal recessive inheritance pattern (usually type IV, Waardenburg-Shah syndrome). A small percentage of cases have been reported in patients with no family history of the disease due to spontaneous mutations.

  • inner ear abnormalities, including aplasia of the posterior semicircular canal 6,7

Treatment of hearing loss includes:

  • hearing augmentation

  • cochlear implantation for severe hearing loss

It is named after P J Waardenburg, a Dutch ophthalmologist and geneticist, who first described the condition in 1951 3.

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