Hirschsprung disease (HSCR) is a frequent congenital malformation (1/5000 live births) ascribed to the absence of parasympathetic intrinsic ganglion cells in the submucosal and myenteric plexuses of the hindgut (1-2). HSCR results in intestinal obstruction in neonates and infants, and severe constipation in adult patients. Various mutations of the RET proto-oncogene have been identified in both familial and sporadic HSCR (3-5). Yet, a body of clinical, genetic and molecular data support the genetic heterogeneity of the disease (2, 6).

On the other hand, Waardenburg syndrome (WS, MIM 193500) is an autosomal dominant malformation syndrome (1/50 000 live births), characterized by congenital deafness, dysmorphic features and pigmentary anomalies of hair, irides and skin (7). Two types of WS have been recognized, based on the presence (WS1) or absence of dystopia canthorum (WS2)(8). Mutations of the Pax 3 gene mapping to the distal long arm of chromosome 2 (2q35-q37)(9) have been found in the majority of WS1 patients (10, 11). Both HSCR and WS are regarded as neurocristopathies (12) related to an abnormal migration of neural crest cells towards either the enteric nervous system (HSCR) or the skin and craniofacial fields (WS). Moreover, the previously described WS/HSCR association (Shah-Waardenburg syndrome or WS 4, MIM 277580)(13-17) is regarded as an autosomal recessive condition, although its mode of inheritance remains debatable (18).