Waardenburg syndrome and Hirschsprung disease: Evidence for pleiotropic effects of a single dominant gene

Segregation and linkage analysis was performed on published data on 5 families segregating for Waardenburg syndrome (WS) and Hirschsprung disease (HRSD). Two of these families demonstrated parental consanguinity. On the basis of these families, autosomal recessive inheritance of the combination WS-HRSD has been postulated. However, a single dominant gene with pleiotropic effects leading to WS and HRSD, with a more severe phenotype in homozygotes, is more plausible. A model of gene action incorporating stochastic effects is compatible with these observations.