Etiology

• Incidence: 1 in 5000 live births

• Sex: ♂ > ♀ (4:1)

• RET gene mutations associated with multiple endocrine neoplasia type 2 (MEN2) and familial Hirschsprung disease

• Endothelin receptor B (EDNRB) gene mutations associated with Waardenburg syndrome

• Trisomy 21

• Multiple endocrine neoplasia type 2 (MEN2)

• Waardenburg syndrome

• Neuroblastoma

• Other conditions: congenital deafness, malrotation, gastric diverticulum, and intestinal atresia

Hirschsprung disease always involves the REcTum and is often associated with RET mutations.

• Hirschsprung disease is caused by defective caudal migration of parasympathetic neuroblasts (precursors of ganglion cells) from the neural crest to the distal colon. This process takes place between the 4th and 7th week of development.

• Affected segments are histologically characterized by the absence of the Meissner plexus and Auerbach plexus (submucosal and myenteric plexus ganglion) beginning at the anorectal line, leading to: [3]

  • Inability of the myenteric plexus to control the intestinal wall muscles → uncoordinated peristalsis and slowed motility

  • Spastic contraction of intestinal muscles → stenosis and functional obstruction

  • Expansion of the colon segment proximal to the aganglionic section (possible megacolon)

• Extent of the disease [2]

  • Ultra-short segment: limited to the distal rectum below the pelvic floor and the anus

  • Short-segment: limited to the rectosigmoid region (approx. 80% of cases)

  • Long-segment: involvement of the distal colon up to the splenic flexure (approx. 10% of cases)

  • Total colonic: entire colon (3–8% of cases)