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Hirschsprung's Disease

The information in NORD’s Rare Disease Database is for educational purposes only. It should never be used for diagnostic or treatment purposes. If you have questions regarding a medical condition, always seek the advice of your physician or other qualified health professional. NORD’s reports provide a brief overview of rare diseases. For more specific information, we encourage you to contact your personal physician or the agencies listed as “Resources” on this report.

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Synonyms of Hirschsprung's Disease

Disorder Subdivisions

General Discussion

Hirschsprung's disease (HSCR) is characterized by the absence of particular nerve cells (ganglions) in a segment of the bowel. The absence of ganglion cells causes the muscles to lose their ability to move the stool through the intestine (peristalsis). Constipation occurs and obstruction of the colon becomes more obvious and perhaps painful. HSCR can occur as an isolated problem or as part of disorder that affects multiple organ systems.

Symptoms

Symptoms of HSCR in the newborn period include failure to pass the meconium within a short time after birth, failure to pass a first stool for 24-48 hours, watery diarrhea and vomiting of green bile. Within a few days there may be signs of constipation, watery diarrhea and possible bacterial toxin production, abdominal swelling (distension), poor weight gain and slow growth.

Initial diagnosis of HSCR is frequently made later in childhood or in adulthood. These individuals often report a lifelong history of constipation.

Causes

HSCR that occurs as an isolated problem has been associated with mutations in at least six different genes. Approximately 50% of affected individuals have one of these gene abnormalities. Inheritance can be dominant or recessive depending on the gene involved, but it is probably necessary for multiple abnormal genes to be present for the disorder to occur. The abnormal genes involved in HSCR can have different effects in members of the same family.

The genes associated with HSCR are in two major groups called RET genes and EDNRB genes. When HRSC involves a short segment of the colon, the major gene involved is the RET gene located on chromosome 10q11.2.

When HSCR occurs along with other abnormalities, the cause is frequently a chromosome abnormality or genetic syndrome.

Affected Populations

Hirschsprung's Disease affects males more often then females. It occurs in approximately one in five thousand live births. It is usually apparent at birth but may also develop in older children and adults. Hirschsprung's Disease should be considered in people with a history of severe constipation.

Related Disorders

Symptoms of the following disorders can be similar to those of Hirschsprung's disease. Comparisons may be useful for a differential diagnosis:

Chronic Intestinal pseudoobstruction is a digestive disorder that may be present at birth. The intestinal walls are unable to contract normally (hypomotility) to generate wave-like (peristaltic) motion. This condition resembles a true obstruction, but no such blockage exists. Abdominal pain, vomiting, diarrhea, constipation, malabsorption of nutrients leading to weight loss and/or failure to thrive, are signal signs. Enlargement of various parts of the small intestine or bowel also occur. (For more information on this disorder, choose " Intestinal pseudoobstruction " as your search term in the Rare Disease Database.)

Neuronal intestinal dysplasia (NID) is characterized by the reduced motility of the large intestine, caused by abnormalities of the enteric nerves. The unusually slow passage of waste through the large intestine leads to chronic problems, such as constipation and uncontrollable soiling. There is no cure. Treatment options include laxatives and surgery.

Irritable bowel disease, commonly called spastic colon or mucous colitis, is a motility disorder that involves both the small intestine and the large bowel. It is characterized by varying degrees of abdominal pain, constipation and diarrhea. Stress makes symptoms worse in affected individuals. Irritable bowel syndrome is a very common disorder. For more information on this disorder, choose "irritable bowel" as your search term in the Rare Disease Database.)

Crohn's disease, also known as ileitis, regional enteritis, or granulomatous colitis, is a form of inflammatory bowel disease characterized by severe, granulomatous, chronic inflammation of the wall of the gastrointestinal tract. In most cases, the ileum is affected. (For more information on this disorder, choose "Crohn" as your search term in the Rare Disease Database.)

Diverticulitis is a common digestive disorder characterized by inflammation of one or more of the sacs (diverticula) that can form due to protrusion of the inner lining of the colon through its wall. It results in pain near the groin in the lower part of the abdomen. Other symptoms may include pain when urinating, constipation, diarrhea or other changes in bowel movements, fever or rectal bleeding. (For more information on this disorder, choose "diverticulitis" as your search term in the Rare Disease Database.)

Hirschsprung's disease is associated with many different chromosome abnormalities and genetic syndromes including the following disorders:

Down syndrome is the most common and readily identifiable genetic condition associated with mental retardation. It is caused by an extra copy of chromosome 21. Many other medical conditions can be associated with Down's such as: congenital heart disease, leukemia, respiratory problems, eye and ear problems and Hirschsprung's Disease. (For more information on this disorder, choose "Down" as your search term in the Rare Disease Database.)

Waardenburg syndrome is a hereditary disorder characterized by facial abnormalities. The inner folds of the eyelids or the tear duct may be displaced, congenital nerve deafness may occur, and often there is abnormal pigmentation of the iris of the eye, the skin and the hair. This disorder is sometimes accompanied by Hirschsprung's disease in both the short and long segments of the large bowel. (For more information on this disorder, choose "Waardenburg" as your search term in the Rare Disease Database.)

Standard Therapies

Diagnosis
Most cases (85-90%) of HSCR are diagnosed in early infancy. The first symptom is usually failure to pass the first bowel movement (meconium). The preferred diagnostic test for HSCR is a suction biopsy of the rectum. Absence of ganglion cells confirms the diagnosis.

Molecular genetic testing for the RET gene is available, but testing for the other genes associated with HSCR is available on a research basis only.

When other abnormalities are present in addition to HSCR, it is possible that the HSCR is due to a chromosomal abnormality or genetic syndrome. Individuals with multiple anomalies should be evaluated by a clinical geneticist in order to attempt to establish an underlying diagnosis.

Treatment
In almost all cases, treatment of HSCR requires surgery to remove the part of the colon and/or rectum that lacks the normal nerve development, and to join the two healthy ends together. There are three standard surgical procedures designed to correct this disorder. The choice of procedure is a function of the training and experience of the surgeon. Each procedure removes the affected part and attaches the healthy part of the bowel to the rectum completing what is known as a "pull-through" procedure.

If the child is very, very young (perhaps less than 6 months) or if he/she is critically ill the surgeon may advise the parents to permit a temporary colostomy in which the diseased part of the colon is removed and the healthy end brought to the surface of the abdomen (stoma). Through this 'stoma' the contents of the colon and rectum are voided into a special bag and removed. After a time, the "pull through" operation is carried out and the abdominal wall opening is closed.

Genetic counseling may be of benefit for patients and their families.

Investigational Therapies

Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.

For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:

Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Organizations related to Hirschsprung's Disease

References

TEXTBOOKS
Peña A, Hong AR. Hirschsprung Disease. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:.

Beers MH, Berkow R., eds. The Merck Manual, 17th ed. Whitehouse Station, NJ: Merck Research Laboratories; 1999:2215-16.

Berkow R., ed. The Merck Manual-Home Edition.2nd ed. Whitehouse Station, NJ: Merck Research Laboratories; 2003:1231.

Yamada T, Alpers DH, Owyang C, et al. Eds. Textbook of Gastroenterology. 2nd ed. J. B. Lippincott Company. Philadephia, PA; 1995:1743-44.

Behrman RE, Kliegman RM, Arvin AM. Eds. Nelson Textbook of Pediatrics. 15th ed. W.B. Saunder Company. Philadelphia, PA; 1996:1070-72.

REVIEW ARTICLES
Teitelbaum DH, Coran AG. Primary pull-through for Hirschsprung's disease. Semin Neonatol. 2003;8:233-41.

Puri P. Intestinal neuronal dysplasia. Semin Pediatr Surg. 2003;12:259-64.

Hajivassiliou CA. Intestinal obstruction in neonatal/pediatric surgery. Semin Pediatr Surg. 2003. 12;241-53.

Stewart DR, von Allmen D. The genetics of Hirschsprung's disease. Gastroenterol Clin North Am. 2003;32:819-37.

Mowat DR, Wilson MJ, Goossens M. Mowat-Wilson syndrome. J Med Genet. 2003;40:305-10.

Teitelbaum DH, Coran AGReoperative surgery for Hirschsprung's disease. Semin Pediatr Surg. 2003;12:124-31.

JOURNAL ARTICLES
Minford JL, Ram A, Turnock RR, et al. Comparison of functional outcomes of Duhamel and transanal endorectal coloanal anastomosis for Hirschsprung's disease. J Pediatr Surg. 2004;39:161-65.

Elhalaby EA, Hashish A, Elbarbary MM, et al. Transanal one-stage endorectal pull-through for hirschsprung's disease: a multicenter study. J Pediatr Surg. 2004;39:345-51.

Puri P, Shinkai T. Pathogenesis of Hirschsprung's disease and its variants: recent progress. Semin Pediatr Surg. 2004;13:18-24.

Hadidi A. Transanal endorectal pull-through for hirschsprung's disease: A comparison with the open technique. Eur J Pediatr Surg. 2003;13:176-80.

Hadidi A. Transanal endorectal pull-through for Hirschsprung's disease: experience with 68 patients.
J Pediatr Surg. 2003;38:1337-40.

Tomita R, Ikeda T, Fujisaki S, et al. Upper gut motility of Hirschsprung's disease and its allied disorders in adults. Hepatogastroenterology. 2003;50:1959-62.

Shah AA, Shah AV. Staged laparoscopic-assisted pull-through for Hirschsprung's disease. J Peiatr Surg. 2003;38:1167-69.

Langer JC, Durrant AC, de la Torre L, et al. One-stage transanal Soave pull-through for Hirschsprung's disease: a multicenter experience with 141 children. Ann Surg. 2003;238:569-83; discussion 583-85.

Griseri P, Pesce B, Patrone G, et al. A rare haplotype of the RET proto-oncogene is a risk-modifying allele in hirschsprung's disease. Am J Hum Genet. 2002;71:969-74.

FROM THE INTERNET
McKusick VA, Ed. Online Mendelian Inheritance in Man(OMIM). The Johns Hopkins University. Hirschsprung Disease. Entry Number; 142623: Last Edit Date; 2/11/2004.

McKusick VA, Ed. Online Mendelian Inheritance in Man (OMIM). The Johns Hopkins University. Hirschsprung Disease 2; HSCR2. Entry Number; 142623: Last Edit Date; 8/27/2001.

What I need to know about Hirschsprung's Disease. National Digestive Disease Information Clearinghouse (NDDIC). December 2001. 13pp.
http://digestive.niddk.nih.gov/ddiseases/pubs/hirschsprungs_ez/

Parisi M, Kapur RP. Hirschsprung Disease Overview. GENEReviews. 12 July 2002. 24 pp.
www.geneclinics.org/servlet/access?id=8888891

Hirschsprung's disease. Institute of Child Health. Great Ormond Street Hospital for Children, NHS Trust. ©GOSH/ICH trust 2002. 4pp.
www.ich.ucl.ac.uk/factsheets/diseases_conditions/hirschsprungs_disease/

Hirschsprung's Disease. pull-thru network. nd. 2pp.
www.pullthrough.org/Hirschsprungs.html

Surgery for Children with Hirschsprung's Disease. A Guide for Patients & Parents. Your Health Matters. UCSF Medical Center. nd. 3pp.

Muir AJ. Hirschsprung's disease. VeriMed Healthcare Network. Review date: 1/12/2003. 3pp.
http://health.allrefer.com/health/hirschsprungs-disease-info.html

Vance A. Hirschsprung's disease. Health A to Z. (Gale Encyclopedia of Medicine). December 2002. 5pp.
www.healthatoz.com/healthatoz/Atoz/ency/hirschsprungs-disease.html

Hirschsprung's Disease (Megacolon). HealthLink. ©Medical College of Wisconsin. 1p.
www.healthlink.mcw.edu/article/930605447.html

Hirschsprung's Disease. eCureMe. ©2003. 5pp.
www.ecureme.com/emyhealth/Pediatrics/Hirschsprung’s_Disease.asp

Hirschsprung's Disease. Cincinnati Children's Hospital Medical Center. Reviewed: 7/03. 3pp.
www.cincinnatichildrens.org/health/info/abdomen/diagnose/hirschsprung.htm

Hirschsprung's Disease. Digestive and Liver Disorders. Lucile Packard Children's Hospital at Stanford. nd. 4pp.
www.lpch.org/DiseaseHealthInfo/HealthLibrary/digest/hirschpr.html

Report last updated: 2008/02/02 00:00:00 GMT+0