Interestingly, there is strong genetic and functional evidence for a role of type I NRG1s in the pathogenesis of HSCR (Tang et al., 2012a), a congenital disorder of the ENS, that is associated with a complete loss of enteric neurons (aganglionosis), since mutations in the NRG1 gene are associated with this disease (Garcia-Barcelo et al., 2009). This evidence concerns the gene NRG1 and Hirschsprung disease.