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- Congenital motor disorder of the gut characterized by lack of ganglion cells in the distal bowel beginning at the anal verge and extending proximally to varying lengths
- Lack of internal anal sphincter (IAS) relaxation and failure of relaxation of the aganglionic segment during peristalsis, producing a functional obstruction.
- Most common cause of lower intestinal obstruction in neonates: 1 in 5,000 births
- Involves the rectum and sigmoid in 75%, descending colon in 14%, whole colon in 8%, and, rarely, small bowel in 3%
- There is familial incidence in total colonic (15–21%) and total intestinal aganglionosis (50%).
- Male predominance with short segment disease ranging from 3:1 to 4:1
- Gender predominance <1:1 in long segment disease.
- Syndromic and nonsyndromic Hirschsprung disease (HD): In the former, there are other congenital anomalies (30% of cases), whereas in the latter, it occurs as an isolated trait.
- Loci implicated include those at chromosomes 3p21, 10q11, 5p13, 22q13, 1p36, and19q12.
- RET proto-oncogene is the major susceptibility gene; mutations of RET account for 50% of familial and 20% of sporadic cases.
- ∼5% of patients with HD have mutations in endothelin signaling pathways
- Defects in and failure of caudal migration of the neural crest cells result in congenital absence of distal enteric nervous system (ENS).
- Basic histologic findings are the absence of ganglion cells in the Meissner and Auerbach plexuses as well as hypertrophied nerve bundles between the circular and the longitudinal muscles and in the submucosa.
Commonly Associated Conditions
- Isolated trait in 70% (nonsyndromic HD)
- Associated malformations in 30% (syndromic HD)
- Chromosomal abnormalities (12%): the most common is trisomy 21 (2–10% of trisomy 21 have HD)
- Congenital birth anomalies (18%): cardiac, limb, sensorineural deafness, central nervous system, genitourinary, and gastrointestinal malformations (anal stenosis, imperforate anus, and small/large bowel atresias)
- Other syndromes associated with HD: Waardenburg syndrome type 4, congenital central hypoventilation syndrome, MEN2, and Smith-Lemli Opitz; dysautonomias