EDNRB and Hirschsprung disease: Collectively, genetic studies of patients with HSCR [32–34] and in vivo transgenic animal models [35–37] have identified multiple genes involved in the development of the ENS, including the receptor tyrosine kinase (RET) [38, 39] and endothelin receptor type B (EDNRB) [40] and their family members as major players for the HSCR phenotype, together with mutations in SOX10 [41, 42], PHOX2B [43], semaphorins [44, 45], among other genes [46].