Indeed, to our knowledge the presence of structural variants in HSCR patients has never or rarely been reported for NRG1, SEMA3A/3D, and PHOX2B. Conversely RET involvement in HSCR does not seem to rely on the presence of CNVs but, interestingly, several gains and losses did co-occur with another RET defect in our sample, thus sustaining the hypothesis that more than one predisposing event is necessary for HSCR to develop. This evidence concerns the gene SEMA3A and Hirschsprung disease.