Hirschsprung Disease



  • 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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