Hirschsprung’s disease is caused by failure of the myentric and submucosal nerve plexuses to migrate craniocaudally into the distal parts of the bowel.

• Normally, the myenteric and submucosal nerve plexuses regulate motility by allowing relaxation of bowel muscles. When the migration of the myenteric and submucosal nerve plexuses to the distal bowel fails, there may be overcontraction, preventing passage of stool.^[1]
• The absence of the myenteric and submucosal nerve plexuses causes overcontraction of rectum smooth muscles, leading to functional obstruction and chronic constipation.
• Absence of these cells in the distal colon is believed to be due to a genetic mutation which may lead to a failure of these cells to migrate craniocaudally.
• Defective differentiation of neuroblasts into neural crest cells is another suggested hypothesis explaining the cause of the disease.^[2]