The authors declare no conflict of interest.
DEVELOPMENTAL BIOLOGY: FRONTIERS FOR CLINICAL GENETICS
The developmental genetics of Hirschsprung's disease
Version of Record online: 7 NOV 2012
© 2012 John Wiley & Sons A/S. Published by Blackwell Publishing Ltd
Volume 83, Issue 1, pages 15–22, January 2013
How to Cite
The developmental genetics of Hirschsprung's disease., , .
- Issue online: 17 DEC 2012
- Version of Record online: 7 NOV 2012
- Accepted manuscript online: 8 OCT 2012 12:28PM EST
- Manuscript Revised: 3 OCT 2012
- Manuscript Accepted: 3 OCT 2012
- Manuscript Received: 2 OCT 2012
- Canadian Institutes for Health Research (CIHR)
- Natural Sciences and Engineering Research Council of Canada (NSERC)
- Fonds de la Recherche du Québec-Santé (FRQS)
- Fonds de la Recherche du Québec-Nature et Technologie (FRQNT)
- aganglionic megacolon;
- enteric nervous system;
- Hirschsprung's disease;
- intestinal motility;
- neural crest cells;
Hirschsprung's disease (HSCR), also known as aganglionic megacolon, derives from a congenital malformation of the enteric nervous system (ENS). It displays an incidence of 1 in 5000 live births with a 4:1 male to female sex ratio. Clinical signs include severe constipation and distended bowel due to a non-motile colon. If left untreated, aganglionic megacolon is lethal. This severe congenital condition is caused by the absence of colonic neural ganglia and thus lack of intrinsic innervation of the colon due in turn to improper colonization of the developing intestines by ENS progenitor cells. These progenitor cells are derived from a transient stem cell population called neural crest cells (NCC). The genetics of HSCR is complex and can involve mutations in multiple genes. However, it is estimated that mutations in known genes account for less than half of the cases of HSCR observed clinically. The male sex bias is currently unexplained. The objective of this review is to provide an overview of the pathophysiology and genetics of HSCR, within the context of our current knowledge of NCC development, sex chromosome genetics and laboratory models.