What is the primary cause of Hirschsprung's disease?

Hirschsprung's disease, also known as congenital aganglionic megacolon, primarily arises from a failure of neural crest cells to properly migrate during embryonic development. These neural crest cells are responsible for forming the enteric nervous system, which controls bowel movements. In Hirschsprung's disease, the absence of these ganglion cells in a segment of the colon leads to a lack of peristalsis in that area, resulting in a functional obstruction. The colonic segment proximal to the affected area becomes dilated, as stool accumulates and is unable to pass through the aganglionic segment.

While genetic mutations do play a role in the predisposition to Hirschsprung's disease, the primary underlying issue is the failure of neural crest cell migration. This cellular migration is crucial in establishing the normal architecture of the enteric nervous system. Environmental factors and infections during pregnancy can potentially influence outcomes for a wide range of conditions, but they are not considered primary causes of Hirschsprung's disease. Understanding the developmental biology of this condition is essential for identifying its causes and implications in affected individuals.