WAARDENBURG-HIRSCHSPRUNG DISEASE IN 2 SISTERS - A POSSIBLE CLUE TO THE GENETICS OF THIS ASSOCIATION

A Tunisian infant of consanguineous parents had pigmentary disorders, congenital deafness and long-segment Hirschsprung disease. Her elder s ister had the same disorders but with short-segment aganglionosis. The ir father mother and two brothers are healthy without history of deafn ess, constipation or pigmentary disorder. We confirm that this Waarden burg-Hirschsprung association seems to be a distinct clinical entity w ith a possible autosomal recessive mode of inheritance. Linkage analys es performed in this family support the view that neither the RET locu s (candidate for familial dominant Hirschsprung disease) nor the HuP(2 ) locus (candidate for Waardenburg syndrome type I) are involved in th e disease phenotype. We suggest that Waardenburg-Hirschsprung complex is a distinct genetic entity and at least one additional locus alterin g cranial neural crest cell development is responsible for pleiotropic features observed in this association.