The FM structural rearrangement results in the duplication of a key regulator of melanoblast and melanocyte proliferation and maintenance, EDN3. Loss of function mutations in EDN3 are associated with pigmentation, auditory and gut innervation disorders in humans (Waardenburg Syndrome and Hirschsprung Disease) [35] and in the mouse (lethal spotting) [36] suggesting a crucial role for EDN3 in regulating NCC-derived lineages. This evidence concerns the gene EDN3 and Hirschsprung disease.