Waardenburg syndrome

Waardenburg syndrome was first reported by van der Hoeve in 1916. In 1951, Waardenburg defined 6 main features: (1) dystopia canthorum, (2) prominent broad nasal root, (3) synophrys, (4) white forelock, (5) heterochromia iridis, and (6) congenital deaf-mutism. Four types of Waardenburg syndrome have now been delineated on the basis of clinical and genetic criteria. The molecular defective gene has been identified in all 4 forms. Patients with Waardenburg syndrome (WS) 1 have a characteristic pleasant feline appearance. In WS2, dystopia canthorum is absent. Deafness and all the facial and hypopigmentation features are due to a disturbance in the neural crest, the origin of melanocytes. The neurosensorial deafness and other neurologic manifestations observed in WS3 and WS4 justify the inclusion of Waardenburg syndrome as a neurocutaneous syndrome. SOX10 mutations in WS4 are associated with a more severe neurologic phenotype: peripheral demyelinating neuropathy, central dysmyelinating leukodystrophy, Waardenburg syndrome, and Hirschsprung disease (PCWH). It has been demonstrated that the same deletions at the SOX10 gene locus may cause WS2 and WS4.