Waardenburg syndrome (WS) is a rare autosomal dominant inherited, clinically and genetically heterogeneous disease. The four clinically defined subtypes have pigmentation disorders of the skin and hair, often with a white forelock, heterochromia iridis, and sensorineural hearing loss, in common. The frequency is reported to be 1:40,000 in the general population. Waardenburg syndrome is thought to be present in 3% of all patients with sensorineural hearing loss.
WS1 and WS2 are the most common forms. They are distinguished by telecanthus and synophris, which do not occur in WS2. WS3 is also known as Waardenburg-Klein syndrome and has upper extremity malformations as an additional main symptom. WS4 or Waardenburg-Shah syndrome shows pigmentation abnormalities and hearing loss in addition to Hirschsprung disease.
The symptoms are caused by differentiation disorders of embryonic cells of the neural crest. The genes known to be causative genes are also involved in the development of the neural crest, the inner ear and the migration of melanocytes.
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