A newborn presents with failure to pass meconium in the first 48 hours. Contrast enema shows a 'transition zone' at the rectosigmoid junction with a dilated proximal colon. Suction rectal biopsy confirms absence of ganglion cells in the submucosal and myenteric plexuses. What embryological failure underlies Hirschsprung's disease?

• A Failure of mesoderm to differentiate into smooth muscle
• B Over-expression of RET proto-oncogene
• C Abnormal endodermal signalling disrupting gut rotation
• D Failure of neural crest cells to migrate caudally to colonise the hindgut ✓

Explanation

Hirschsprung's disease results from failure of neural crest-derived ganglion cell precursors to migrate craniocaudally along the hindgut to reach the rectum by 12 weeks of gestation. The aganglionic segment (always starts at the internal anal sphincter and extends proximally) is tonically contracted because of the absence of the inhibitory myenteric plexus. Loss-of-function mutations in the RET proto-oncogene and its co-receptor GDNF are the most common genetic causes; RET is not over-expressed but rather lost.

Reference: Bailey & Love's Short Practice of Surgery, 27th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.