Discrepancy between macroscopic and microscopic transitional zones in Hirschsprung's disease with reference to the type of RET/GDNF/SOX10 gene mutation

Abstract

Background/purpose: Recent studies have found that Hirschsrung's disease is caused by diverse genomic abnormalities. To clarify whether these pathogenic variations influence the distribution and function of enteric ganglia, the authors studied the morphology of the macroscopic and microscopic transitional zone in Hirschsprung's disease with reference to the type of genetic mutation.

Methods: In 120 patients with Hirschsprung's disease, the location and morphology of the gut caliber change were recorded, and the enteric nervous system was investigated histologically using biopsy specimens. The DNA sequences of all the RET/GDNF/NTN and SOX10 coding regions were determined using the direct DyeDeoxy Terminator Cycle method.

Results: In RET mutation carriers, the gut caliber change was almost identical to the histologic transition in cases of short segment aganglionosis, whereas these were markedly dissociated in cases exhibiting extensive aganglionosis. In contrast, SOX10 mutation carriers had a very long histologic transition and exhibited no caliber change.

Conclusions: The type of genetic mutation responsible for Hirschsprung's disease influences the postnatal distribution and function of enteric ganglia. The data on discrepancy between macroscopic and microscopic transitions may enable us to concentrate the sites of the leveling biopsy more accurately especially in cases of long type intestinal aganglionosis carrying RET gene mutation.