Hirschsprung’s disease

Synonyms

1

Overview

Hirschsprung's disease (HD) is a form of megacolon that occurs when part or all of the large intestine or antecedent parts of the gastrointestinal tract have no ganglion cells and therefore cannot function. 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). In Hirschsprung's disease, the migration is not complete and part of the colon lacks these nerve bodies that regulate the activity of the colon. The affected segment of the colon cannot relax and pass stool through the colon, creating an obstruction. In most affected people, the disorder affects the part of the colon that is nearest the anus. In rare cases, the lack of nerve bodies involves more of the colon. In five percent of cases, the entire colon is affected. Stomach and esophagus may be affected too.

Hirschsprung's disease occurs in about one in 5,000 of live births. It is usually diagnosed in children, and affects boys more often than girls. About 10% of cases are familial.

Symptoms

Typically, Hirschsprung's 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) within 48 hours of delivery. Normally, 90% of babies pass their first meconium within 24 hours, and 99% within 48 hours. Other symptoms include green or brown vomit, explosive stools after a doctor inserts a finger into the rectum, swelling of the abdomen, lots of gas and bloody diarrhea.

Some cases are diagnosed later, into childhood, but usually before age 10. The child may experience fecal retention, constipation, or abdominal distention. With an incidence of one in 5,000 births, the most cited feature is absence of ganglion cells: notably in males, 75 percent have none in the end of the colon (recto-sigmoid) and eight percent lack ganglion cells in the entire colon. The enlarged section of the bowel is found proximally, while the narrowed, aganglionic section is found distally, closer to the end of the bowel. The absence of ganglion cells results in a persistent over-stimulation of nerves in the affected region, resulting in contraction.

In some extremely rare cases, the absence of ganglion cells continues to spread after the corrective surgery, resulting in multiple surgeries.

Those patients that also have thyroid cancer may be able to digest food properly, but may not be able to use the nutrients properly.

Causes

Isolated Hirschsprung disease can result from mutations in one of several genes, including the RET,EDNRB, and EDN3 genes. However, the genetics of this condition appear complex and are not completely understood. While a mutation in a single gene sometimes causes the condition, mutations in multiple genes may be required in some cases. The genetic cause of the condition is unknown in approximately half of affected individuals.

Mutations in the RET gene are the most common known genetic cause of Hirschsprung disease. TheRET gene provides instructions for producing a protein that is involved in signaling within cells. This protein appears to be essential for the normal development of several kinds of nerve cells, including nerves in the intestine. Mutations in the RET gene that cause Hirschsprung disease result in a nonfunctional version of the RET protein that cannot transmit signals within cells. Without RET protein signaling, enteric nerves do not develop properly. Absence of these nerves leads to the intestinal problems characteristic of Hirschsprung disease.

The EDNRB gene provides instructions for making a protein called endothelin receptor type B. When this protein interacts with other proteins called endothelins, it transmits information from outside the cell to inside the cell, signaling for many important cellular processes. The EDN3 gene provides instructions for a protein called endothelin 3, one of the endothelins that interacts with endothelin receptor type B. Together, endothelin 3 and endothelin receptor type B play an important role in the normal formation of enteric nerves. Changes in either the EDNRB gene or the EDN3 gene disrupt the normal functioning of the endothelin receptor type B or the endothelin 3 protein, preventing them from transmitting signals important for the development of enteric nerves. As a result, these nerves do not form normally during embryonic development. A lack of enteric nerves prevents stool from being moved through the intestine, leading to severe constipation and intestinal blockage.

Read more about the EDN3, EDNRB, and RET genes.

See a list of genes associated with Hirschsprung disease.

Diagnosis

Definitive diagnosis is made by suction biopsy of the distally narrowed segment. 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 Hirschsprung's 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.

Prognosis

Symptoms improve or are eliminated in most children after surgical treatment. A better outcome is associated with early treatment and shorter bowel segment involvement.

Treatment

Treatment of Hirschsprung's 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 child’s 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.

Swenson, Soave, Duhamel, and Boley procedures

Orvar Swenson, who discovered the cause of Hirschsprung’s, 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 Hirschsprung’s in younger patients. Swenson devised the original procedure, and the pull-through surgery has been modified many times.

Currently, there are several different surgical approaches, which include the Swenson, Soave, Duhamel, and Boley procedures. The Swenson procedure leaves a small portion of the diseased bowel. The Soave procedure leaves the outer wall of the colon unaltered. The Boley procedure is a small modification of the Soave procedure, so the term "Soave-Boley" procedure is sometimes used. The Duhamel procedure uses a surgical stapler to connect the good and bad bowel.

For the 15 percent of children who do not obtain full bowel control, other treatments are available. Constipation may be remedied by laxatives or a high fiber diet. In those patients, serious dehydration can play a major factor in their lifestyle. A lack of bowel control may be addressed by a stoma, similar to a colostomy. The Malone antegrade colonic enema (ACE) is also an option. In a Malone ACE, a tube goes through the abdominal wall to the appendix or, if available, to the colon. The bowel is then flushed daily. Children as young as 6 years of age may administer this daily flush on their own.

If the affected portion of the lower intestine is restricted to the lower portion of the rectum, other surgical procedures may be performed, such as a posterior rectal myectomy.

The prognosis is good in 70 percent of cases. Chronic post-operative constipation is present in 7 to 8 percent of the operated cases. Post-operative enterocolitis is a severe manifestation that is present in the 10%–20% of operated patients.