[Durgical](https://durgical.com/en/) › [DurgiPedia](https://durgical.com/en/durgipedia/) › [General pathology](https://durgical.com/en/general-pathology/) › [Gastrointestinal tract](https://durgical.com/en/general-pathology/areas/gi/) › Hirschsprung disease # Hirschsprung disease - Lesion Nerve cells never reach the end of the colon, so that segment cannot relax; stool backs up and the bowel above swells. Updated Nov 12, 2026 ## Key points - The rectum is always involved; the aganglionic zone extends upward for a variable length, usually to the sigmoid (short-segment disease is commonest). - Diagnosis needs a rectal biopsy showing absent ganglion cells. - Loss-of-function RET mutations cause most familial and some sporadic cases; EDNRB and EDN3 are other genes. - Associated with Down syndrome and male sex. - Failure to pass meconium in the first 48 hours, then distension and bilious vomiting. - The dilated part is the normal bowel; the narrow part is the diseased one. ## What it is Hirschsprung disease (congenital aganglionic megacolon) is a functional obstruction of the distal colon. Neural crest cells that form the enteric nerve plexuses normally migrate from the caecum to the rectum; when migration stops early or the cells die, a distal segment lacks both the submucosal (Meissner) and myenteric (Auerbach) plexuses. That segment stays contracted, and the normal bowel above it dilates. ## Structure - Gross: a narrow or normal-looking distal segment with marked dilation of the proximal colon (megacolon). - Micro: no ganglion cells in submucosal or myenteric plexuses; often thick hypertrophic nerve fibres. - Acetylcholinesterase staining shows the thick nerve fibres; calretinin staining is lost in the aganglionic segment. - The stretched proximal wall may ulcerate or rupture, most often near the caecum. ## Step by step - Neural crest cells migrate along the gut from proximal to distal during embryonic life. - RET or endothelin signalling fails, so migration stops or the cells die early. - The distal segment has no enteric neurons and cannot relax. - Peristalsis cannot pass the segment: a functional obstruction. - Stool accumulates and the innervated colon above dilates. ## Markers - Absent ganglion cells (H&E) - Acetylcholinesterase: thick nerve fibres - Calretinin: lost ## Clinical notes - Hirschsprung-associated enterocolitis is a dangerous complication before or after surgery. - Acquired megacolon with ganglion cell loss occurs in Chagas disease (Trypanosoma cruzi), a Latin American cause to remember; other acquired megacolons (tumour, stricture, ulcerative colitis) keep their ganglia. ## Memory aid No crest, no rest: the narrow segment never relaxes, and the healthy bowel above pays for it. ## Test yourself Think of the answer, then tap the question to see it. ## Which segment of the colon is always aganglionic in Hirschsprung disease? The rectum; the disease extends proximally from there for a variable distance. ## In Hirschsprung disease, which part of the bowel is dilated? The normally innervated bowel proximal to the aganglionic segment. ## Which gene is most often mutated in familial Hirschsprung disease? RET, a receptor tyrosine kinase needed for migration of neural crest precursors. ## Which infection causes acquired megacolon with loss of ganglion cells? Chagas disease, through destruction of the myenteric plexus by Trypanosoma cruzi. [Add to my cards (4)](https://durgical.app/estudiar/?add=/en/general-pathology/hirschsprung-disease/) [More Pathology questions →](https://durgical.com/en/practice/?f=pathology) ## Elsewhere in DurgiPedia - [Hirschsprung disease (congenital aganglionic megacolon)](https://durgical.com/en/embryology/hirschsprung-disease/) - [The enteric nervous system, slow waves and GI control](https://durgical.com/en/physiology/the-enteric-nervous-system-slow-waves-and-gi-control/) ## Connections ## Related 5 - [Congenital anomalies of the gut](https://durgical.com/en/general-pathology/congenital-anomalies-of-the-gut/) - [Achalasia and other motor disorders: loss of the inhibitory neurons](https://durgical.com/en/general-pathology/achalasia-and-other-motor-disorders-loss-of-the-inhibitory-neurons/) - [Intestinal obstruction](https://durgical.com/en/general-pathology/intestinal-obstruction/) - [Immunohistochemistry: the principle and the markers to know](https://durgical.com/en/general-pathology/immunohistochemistry-the-principle-and-the-markers-to-know/) - [Trisomies 21, 18 and 13, and the 22q11.2 deletion](https://durgical.com/en/general-pathology/trisomies-21-18-and-13-and-the-22q11-2-deletion/) ## Related conditions 3 - [Hirschsprung disease](https://durgical.com/en/conditions/hirschsprung-disease/) - [Chagasic megaoesophagus and megacolon](https://durgical.com/en/conditions/chagasic-megaoesophagus-and-megacolon/) - [Constipation and faecal impaction](https://durgical.com/en/conditions/constipation-and-faecal-impaction/) [← All of general pathology](https://durgical.com/en/general-pathology/) Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given. Sources: [Hirschsprung disease: MedlinePlus Medical Encyclopedia](https://medlineplus.gov/ency/article/001140.htm) (MedlinePlus, US National Library of Medicine, 2025); [Hirschsprung disease: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/hirschsprung-disease/) (MedlinePlus, US National Library of Medicine, 2025). ## **Spotted a mistake?** We are always improving for the community. Tell us what is wrong and our team will review it. Report a mistake Representative model, for educational purposes only. --- Source: https://durgical.com/en/general-pathology/hirschsprung-disease/ License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/hirschsprung-disease/