Variants of at least eleven genes to date have been implicated in Hirschsprung disease including the two major ones, RET (receptor tyrosine kinase) and EDNRB (endothelin receptor type B), whereas these mutations account for only 50% of familial and up to 20% sporadic subjects with HSCR, and cumulatively explain a small proportion of the heritability [5]. This evidence concerns the gene RET and Hirschsprung disease.