GDNF and Hirschsprung disease: In recent years, more than a dozen genes related to the pathogenesis of HSCR were confirmed, including RET [12], EDNRB [13], SOX10 [14], GDNF [15], EDN3 [16], PHOX2B [17,18], etc. However, these gene mutations associated with the onset of HSCR are only half of current HSCR cases [6].