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Congenital aganglionic megacolon (Hirschsprung disease)

David E Wesson, MD
Section Editors
Jonathan I Singer, MD
Deputy Editor
Alison G Hoppin, MD


Hirschsprung disease (HD) is a motor disorder of the gut, which is caused by the failure of neural crest cells (precursors of enteric ganglion cells) to migrate completely during intestinal development during fetal life. The resulting aganglionic segment of the colon fails to relax, causing a functional obstruction.

In about 80 percent of patients, the disorder affects the rectosigmoid colon (known as short-segment disease) [1,2]. In 15 to 20 percent of patients, the aganglionosis extends proximal to the sigmoid colon (known as long-segment disease). In approximately 5 percent, the entire colon is affected (known as total colonic aganglionosis [TCA]), and in rare cases the small bowel may also be involved. Outcomes are generally worse for patients with long-segment as compared with short-segment disease.

The pathogenesis, diagnosis, and clinical management of HD are discussed below. The emergency complications of HD, including acute obstruction in the neonate, Hirschsprung-associated enterocolitis, and volvulus, are discussed in a separate topic review. (See "Emergency complications of Hirschsprung disease".)


Hirschsprung disease (HD) occurs in approximately 1 in 5000 live births with an overall male:female ratio of 3:1 to 4:1; when the entire colon is involved, the gender ratio more nearly approaches 1:1 [3-5]. There is familial clustering for nonsyndromic HD, with an overall recurrence risk of about 3 percent in siblings for short-segment disease, or up to 17 percent if the proband has long-segment disease [2]. This recurrence risk is higher if the proband is a female, and is also higher if multiple family members are affected.


The most accepted theory of the cause of Hirschsprung disease (HD) is that there is a defect in the craniocaudal migration of neuroblasts originating from the neural crest, a process that begins at four weeks of gestation and ends at week 7 with the arrival of neural crest-derived cells at the distal end of the colon [6]. Failure of the cells to reach the distal colon leaves that segment aganglionic and therefore nonfunctional, resulting in Hirschsprung disease. Defects in the differentiation of neuroblasts into ganglion cells and ganglion cell destruction within the intestine may also contribute to the disorder [7].


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Literature review current through: Jul 2017. | This topic last updated: Aug 04, 2017.
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