Hirschsprung Disease

Basics

Described in 1886 by Harold Hirschsprung as a cause of constipation in early infancy
Congenital aganglionosis megacolon
1:5,000 live births
Overall mortality of Hirschsprung enterocolitis is 35–50%

Absence of enteric ganglia in the distal bowel
Normally, ganglia are derived from neural crest and migrate along the intestine, arriving at the proximal colon by 8 wk of gestation and in the rectum by 12 wk of gestation
Failure of neural crest cells to migrate into parasympathetic Meissner (submucosal) and Auerbach (myenteric) ganglions results in an aganglionic segment and clinical disease
Affected bowel classically presents at the internal anal sphincter and involves the rectosigmoid colon (75% of cases)
May extend the entire length of the GI tract (often fatal)
Aganglionic segment chronically contracts, forming an obstruction to the passage of stool, and proximal bowel distends to hold the stool that has not passed
Stimulation of the anus allows passage of stool
Genetic and other causes
- Mutations of the ret proto-oncogene found in both familial and spontaneous forms
- Male-to-female ratio 4:1:
  - 8% with positive family history; 5–12% of siblings are affected
  - Associated chromosomal abnormality in 5–15%, most commonly trisomy 21 (Down syndrome)
  - Other congenital anomalies in 18%—GI, cardiac, craniofacial, cleft palate, congenital deafness

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