GDNF and Hirschsprung disease: Hirschsprung’s disease, the main genetic cause of chronic life-endangering constipation with a frequency of 1:5000 live births, results in many cases from mutations in specific genes, such as Ret or Gdnf, implicated in differentiation or patterning of the enteric nervous system, giving rise to an aganglionic megacolon [48,49].