Waardenburg syndrome - Definition and Overview

Waardenburg syndrome is an inherited disorder associated with hearing loss and changes in skin and hair pigmentation. The syndrome is named for Dutch ophthalmologist Petrus Johannes Waardenburg who first described it.

Pigmentation changes may include irises of varying color (heterochromia iridis), or a patch of white or grey hair. Hearing loss may be absent, moderate, or profound.

There are several subtypes of the syndrome, traceable to different genetic variations. Dystopia canthorum, a widened bridge of the nose because of lateral displacement of the inner canthus of each eye, is associated with type I.

• Type I is associated with mutations in the paired box gene 3 (PAX3) gene located at 2q35.
• Type IIa is associated with mutations in the microphthalmia-associated transcription factor (MITF) gene located at 3p14.1-p12.3
• Type IIb is associated with a locus designated WS2B at 1p21-p13.3
• Type IIc is associated with a locus designated WS2C at 8p23
• Type III is associated with mutations in the paired box gene 3 (PAX3) gene located at 2q35.
• Type IV, Waardenberg-Hirschsprung disease, or Waardenburg-Shah syndrome, is associated with mutations in the endothelin-B receptor gene (EDNRB), the gene for its ligand, endothelin-3 (EDN3), or in the SRY-related HMG-box gene 10 (SOX10) gene, which are located at 22q13, 20q13.2-q13.3. This subtype may include neurologic manifestations.