Genetics of Hirschsprung disease and anorectal malformations

Semin Pediatr Surg. 2010 May;19(2):107-17. doi: 10.1053/j.sempedsurg.2009.11.015.


Hirschsprung disease (HD) and anorectal malformations (ARMs) result from alterations in hindgut development. It has long been recognized that both recur in families and thus result, at least in part, from genetic factors. Progress in the understanding of the genetic basis of HD has been made by the application of findings from genetic animal models of altered enteric nervous system development to human beings. Several genes have been shown to be important for human enteric nervous system development, and current work is progressing to identify genetic interactions that may explain the variable phenotype of HD. By contrast, understanding of the genetic factors underlying ARMs is much less developed. We and others have shown that genetic factors play an important role in the pathogenesis of ARMs, and many mouse genetic models suggest molecular pathways that may be altered in ARMs.

Publication types

  • Review

MeSH terms

  • Anal Canal / abnormalities
  • Animals
  • Digestive System Abnormalities / genetics*
  • Disease Models, Animal
  • Genetic Predisposition to Disease / genetics
  • Glial Cell Line-Derived Neurotrophic Factor / genetics
  • Hirschsprung Disease / genetics*
  • Hirschsprung Disease / physiopathology
  • Humans
  • Pedigree
  • Proto-Oncogene Proteins c-ret / genetics
  • Rectum / abnormalities
  • Signal Transduction / genetics


  • Glial Cell Line-Derived Neurotrophic Factor
  • Proto-Oncogene Proteins c-ret