Hirschsprung's disease (HD or HSCR) is a birth defect in which nerves are missing from parts of the intestine.

[1] The condition is believed to have first been described in 1691 by Dutch anatomist Frederik Ruysch[6] and is named after Danish physician Harald Hirschsprung following his description in 1888.

[7][8] Typically, Hirschsprung disease is diagnosed shortly after birth, although it may develop well into adulthood, because of the presence of megacolon, or because the baby fails to pass the first stool (meconium)[9] within 48 hours of delivery.

In older children, some other signs and symptoms include chronic constipation, flatulence, swollen belly, fatigue, and failure to thrive.

[2] Several genes and specific regions on chromosomes (loci) have been shown or suggested to be associated with Hirschsprung's disease[citation needed] The RET proto-oncogene accounts for the highest proportion of both familial and sporadic cases, with a wide range of mutations scattered along its entire coding region.

[21] RET is a gene that codes for proteins that assist cells of the neural crest in their movement through the digestive tract during the development of the embryo.

[22] Also, new research suggests that mutations in genomic sequences involved in regulating EDNRB have a bigger impact on Hirschsprung's disease than previously thought.

One function that RET controls is the travel of the neural crest cells through the intestines in the developing fetus.

[citation needed] Common and rare DNA variations in the neuregulin 1 (NRG1) and NRG3 (NRG3) were first shown to be associated with the disease in Chinese patients through a Genome Wide Association Study by the Hong Kong team in 2009 [23] and 2012, respectively[24] Subsequent studies in both Asian and Caucasian patients confirmed the initial findings by the University of Hong Kong.

Both rare and common variants in these two genes have been identified in additional Chinese,[25] Thai, Korean, Indonesian, and Spanish patients.

These two genes are known to play a role in the formation of the enteric nervous system; thus, they are likely to be involved in the pathology of Hirschsprung's disease, at least in some cases.

[citation needed] Another gene associated with this condition is NADPH oxidase, EF-hand calcium binding domain 5 (NOX5).

[27] The most accepted theory of the cause of Hirschsprung is a defect in the craniocaudal migration of neuroblasts originating from the neural crest that occurs during the first 12 weeks of gestation.

[9] With Hirschsprung's disease, the segment lacking neurons (aganglionic) becomes constricted, causing the normal, proximal section of bowel to become distended with feces.

This narrowing of the distal colon and the failure of relaxation in the aganglionic segment are thought to be caused by the lack of neurons containing nitric oxide synthase.

The suction rectal biopsy is considered the current international gold standard in the diagnosis of Hirschsprung's disease.

[34] Cineanography (fluoroscopy of contrast medium passing anorectal region) assists in determining the level of the affected intestines.

[35] Treatment of Hirschsprung's disease consists of surgical removal (resection) of the abnormal section of the colon, followed by reanastomosis.

In this approach, the healthy end of the large intestine is cut and attached to an opening created on the front of the abdomen.

[citation needed] The Swedish-American surgeon Orvar Swenson (1909–2012), who discovered the cause of Hirschsprung's, first performed its surgical treatment, the pull-through surgery, in 1948.

[37]' Currently, several different surgical approaches are used, which include the Swenson, Soave, Duhamel, and Boley procedures.

A lack of bowel control may be addressed by an ileostomy – similar to a colostomy, but uses the end of the small intestine rather than the colon.

[citation needed] The first publication on an important genetic discovery of the disease was from Martucciello Giuseppe et al. in 1992.

However, in August 1993, two articles by independent groups in Nature Genetics said that Hirschsprung's disease could be mapped to a stretch of chromosome 10.