A study by Watanabe in 1998 showed that PAX3 transactivates the MITF promotor. Mutations in the PAX3 gene, therefore, could affect regulation of the MITF gene, leading to abnormalities of melanocyte differentiation. Heterozygous mutations in either gene cause isolated Hirschsprung disease. Heterozygous mutations in the SOX10 gene also reportedly cause WS4. The SOX10 gene interacts with PAX3 in regulating the MITF gene.
Mortality is comparable to unaffected individuals.
WS has no known racial or ethnic predilection. Males and females are affected equally. In 1992, the Waardenburg Syndrome Consortium proposed diagnostic criteria for WS1. Individuals should be considered affected with WS1 if they have 2 major or 1 major plus 2 minor criteria from the list below. In 1995, Lui et al used the same list to define WS2 as individuals with 2 major features who do not have dystopia canthorum.