[Increased expression of HOXA9 gene in Hirschsprung disease]

Hirschsprung disease is characterized by segmental aganglionosis of the terminal bowel. Neurons of the enteric nervous system arise from neural crest, migrate and colonize intestinal muscle coat where they proliferate and differentiate. The first pathophysiologic hypothesis suggests an absence of neural cell migration. The most recent hypothesis involves disorders of their homing and/or their differentiation due to an altered intestinal microenvironment.

We analyzed the expression of muscle markers and laminin isoforms by immunocytochemistry and of homeotic genes involved in the regionalization of the intestinal mesenchyme during development (HOXA4, HOXA9, HOXD9) by RT-PCR, in colon specimens from two children with Hirschsprung disease (pathological and transition regions) and from healthy adult controls.

We showed an increase in HOXA9 gene expression in Hirschsprung disease specimens while HOXA4 and HOXD9 mRNA expressions were unchanged. No significant differences in the muscle markers nor in the laminin isoforms were noted.

These data suggest that intrinsic dysregulation of the intestinal wall microenvironment could account for the pathophysiology of Hirschsprung disease.