Waardenburg syndrome

Abstract

Auditory-pigmentary syndromes are caused by physical absence of melanocytes from the skin, hair, eyes, or the stria vascularis of the cochlea. Dominantly inherited examples with patchy depigmentation are usually labelled Waardenburg syndrome (WS). Type I WS, characterised by dystopia canthorum, is caused by loss of function mutations in the PAX3 gene. Type III WS (Klein-Waardenburg syndrome, with abnormalities of the arms) is an extreme presentation of type I; some but not all patients are homozygotes. Type IV WS (Shah-Waardenburg syndrome with Hirschsprung disease) can be caused by mutations in the genes for endothelin-3 or one of its receptors, EDNRB. Type II WS is a heterogeneous group, about 15% of whom are heterozygous for mutations in the MITF (microphthalmia associated transcription factor) gene. All these forms show marked variability even within families, and at present it is not possible to predict the severity, even when a mutation is detected. Characterising the genes is helping to unravel important developmental pathways in the neural crest and its derivatives.