The recent identification of a deletion encompassing the SOX10 regulatory elements U1 and U3 in a patient with WS4 [24], as well as their functional importance during enteric nervous system development ([22] and our unpublished observations), opens the possibility that variations within regulatory sequences could be at the origin of other phenotypes, or play a role in phenotypic variability. This evidence concerns the gene SOX10 and Waardenburg-Shah syndrome.