Both of these disorders are more common in Hirschsprungs patients than in the general population. One function that RET controls is the travel of the neural crest cells through the intestines in the developing fetus. The earlier the RET mutation occurs in Hirschsprungs disease, the more severe the disorder becomes. Other genes
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  and 2012, respectively 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, 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 Hirschsprungs disease, at least in some cases.Another gene associated with this condition is NADPH oxidase, EF-hand calcium binding domain 5 (NOX5). This gene is located on the long arm of chromosome 15 (15q23). Pathophysiology
During normal prenatal development, cells from the neural crest migrate into the large intestine (colon) to form the networks of nerves called the myenteric plexus (Auerbach plexus) (between the smooth muscle layers of the gastrointestinal tract wall) and the submucosal plexus (Meissner plexus) (within the submucosa of the gastrointestinal tract wall).
A histologic examination of the tissue would show a lack of ganglionic nerve cells. Diagnostic techniques involve anorectal manometry, barium enema, and rectal biopsy. The suction rectal biopsy is considered the current international gold standard in the diagnosis of Hirschsprungs disease.Radiologic findings may also assist with diagnosis. Cineanography (fluoroscopy of contrast medium passing anorectal region) assists in determining the level of the affected intestines. Treatment
Treatment of Hirschsprungs disease consists of surgical removal (resection) of the abnormal section of the colon, followed by reanastomosis. Colostomy
The first stage of treatment used to be a reversible colostomy. In this approach, the healthy end of the large intestine is cut and attached to an opening created on the front of the abdomen. The contents of the bowel are discharged through the hole in the abdomen and into a bag. Later, when the patients weight, age, and condition are right, the "new" functional end of the bowel is connected with the anus. The first surgical treatment involving surgical resection followed by reanastomosis without a colostomy occurred as early as 1933 by Doctor Baird in Birmingham on a one-year-old boy. Other procedures
The Swedish-American surgeon Orvar Swenson (1909–2012), who discovered the cause of Hirschsprungs, first performed its surgical treatment, the pull-through surgery, in 1948. The pull-through procedure repairs the colon by connecting the functioning portion of the bowel to the anus. The pull-through procedure is the typical method for treating Hirschsprungs in younger patients. Swenson devised the original procedure, and the pull-through surgery has been modified many times.