DESCRIPTION

Developmental disorder of the enteric nervous system characterized by the absence of ganglion cells in the distal bowel beginning at the anorectal junction and extending proximally to varying lengths, which results in a functional intestinal obstruction

EPIDEMIOLOGY

• Most common cause of distal intestinal obstruction in neonates: 1 in 5,000 births
• Aganglionosis extends to the rectum and sigmoid colon in 80% of cases, descending colon in 10%, total colon in 8%, and into the small bowel in 3%.
• There is familial incidence in total colonic (15–21%) and total intestinal aganglionosis (50%).
• Male-to-female ratio of Hirschsprung disease (HD) is 4:1 for short segment disease.
• Syndromic and nonsyndromic HD: In the former, there are other congenital anomalies (30% of cases), whereas in the latter, it occurs as an isolated trait.

RISK FACTORS

PATHOPHYSIOLOGY

• Normal development of the enteric nervous system requires a proximal to distal migration of neural crest cells through the gastrointestinal tract, after which they differentiate into mature ganglion cells.
• Incomplete caudal migration, differentiation, or survival of the neural crest cells result in the absence of distal intestinal ganglion cells and a functional intestinal obstruction due to the lack of peristalsis.
• Basic histologic findings are the absence of ganglion cells and the presence of hypertrophied nerve bundles in the submucosal or myenteric plexuses of the intestine.

COMMONLY ASSOCIATED CONDITIONS

• Isolated trait in 70% (nonsyndromic HD)
• Associated malformations in 30% (syndromic HD)
• Syndromes associated with HD:
  • Down syndrome (trisomy 21)
  • Waardenburg syndrome type 4
  • Congenital central hypoventilation syndrome (Ondine’s curse)
  • Multiple endocrine neoplasia type 2
  • Smith-Lemli-Opitz syndrome
  • Goldberg-Shprintzen syndrome
  • Cartilage-hair hypoplasia syndrome
  • Familial dysautonomia