EDN3 and Hirschsprung disease: Sánchez-Mejías et al. (2009) reported a Hirschsprung disease family in which mutations in three different genes (RET, NTRK3 and EDN3) contributed to the disease phenotype; the RET and NTRK3 mutations were both necessary and sufficient to give rise to the clinical phenotype, whereas the EDN3 mutation appeared to act as a modifier.