Hirschsprung's disease (congenital aganglionic megacolon) results from failure of which embryological cell migration, and at what embryological week does this migration normally complete?
- A Lateral plate mesoderm fails to surround the gut to form smooth muscle by week 8
- B Entoderm-derived cells fail to differentiate into goblet cells in the rectum
- C Neural crest cells (from vagal and sacral neural crest) fail to migrate caudally into the gut wall to form the myenteric and submucosal plexuses; migration normally completed by week 12 ✓
- D Paraxial mesoderm fails to segment to form the enteric ganglia
Explanation
The enteric nervous system ganglia (myenteric/Auerbach's plexus and submucosal/Meissner's plexus) are derived from neural crest cells. Vagal neural crest cells migrate cranio-caudally, and sacral neural crest cells migrate in the opposite direction, to populate the enteric plexuses by approximately week 12 of embryonic life. In Hirschsprung's disease, neural crest migration arrests before reaching the distal rectum (the most common affected segment), leaving an aganglionic segment that cannot relax (functional obstruction). The RET proto-oncogene mutation is the most common genetic cause. The aganglionic bowel is always the distal-most segment.
Reference: BD Chaurasia's Human Anatomy, 8th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.