eMedicine Specialties > Pediatrics: General Medicine > Gastroenterology

Hirschsprung Disease

Author: Holly L Neville, MD, Assistant Professor of Clinical Surgery, Division of Pediatric Surgery, University of Miami Miller School of Medicine
Contributor Information and Disclosures

Updated: Nov 17, 2008

Introduction

Background

In 1886, Harold Hirschsprung first described Hirschsprung disease as a cause of constipation in early infancy. Early recognition and surgical correction of Hirschsprung disease protects affected infants from enterocolitis and debilitating constipation.

Pathophysiology

Hirschsprung disease results from the absence of enteric neurons within the myenteric and submucosal plexus of the rectum and/or colon. Enteric neurons are derived from the neural crest and migrate caudally with the vagal nerve fibers along the intestine. These ganglion cells arrive in the proximal colon by 8 weeks' gestation and in the rectum by 12 weeks' gestation. Arrest in migration leads to an aganglionic segment. This results in clinical Hirschsprung disease.

Frequency

United States

Hirschsprung disease occurs in approximately 1 per 5000 live births.

International

Prevalence may vary by region and has been shown to be as high as 1 per 3000 live births in the Federated States of Micronesia.1

Mortality/Morbidity

The overall mortality of Hirschsprung enterocolitis is 25-30%, which accounts for almost all of the mortality from Hirschsprung disease.

Sex

Hirschsprung disease is approximately 4 times more common in males than females.

Age

Nearly all children with Hirschsprung disease are diagnosed during the first 2 years of life. Approximately one half of children affected with this disease are diagnosed before they are aged 1 year. A small number of children with Hirschsprung disease are not recognized until much later in childhood or adulthood.

Clinical

History

  • During the newborn period, infants affected with Hirschsprung disease may present with abdominal distention, failure of passage of meconium within the first 48 hours of life, and repeated vomiting. A family history of a similar condition is present in about 30% of cases.
  • Nearly one half of all infants with Hirschsprung disease have a history of delayed first passage of meconium (beyond age 36 h), and nearly one half of infants with delayed first passage of meconium have Hirschsprung disease.
  • Unlike children experiencing functional constipation, children with Hirschsprung disease rarely experience soiling and overflow incontinence.
  • Children with Hirschsprung disease may be malnourished. Poor nutrition results from the early satiety, abdominal discomfort, and distention associated with chronic constipation.
  • Older infants and children typically present with chronic constipation. This constipation often is refractory to usual treatment protocols and may require daily enema therapy.
  • Hirschsprung enterocolitis can be a fatal complication of Hirschsprung disease. Enterocolitis typically presents with abdominal pain, fever, foul-smelling and/or bloody diarrhea, as well as vomiting. If not recognized early, enterocolitis may progress to sepsis, transmural intestinal necrosis, and perforation.

Physical

  • Examination of infants affected with Hirschsprung disease reveals tympanitic abdominal distention and symptoms of intestinal obstruction. Individuals in this age group may also present with acute enterocolitis or with neonatal meconium plug syndrome.
  • Children with Hirschsprung disease are usually diagnosed by age 2 years.
    • Older infants and children with Hirschsprung disease usually present with chronic constipation. Upon abdominal examination, these children may demonstrate marked abdominal distention with palpable dilated loops of colon. Rectal examination commonly reveals an empty rectal vault and may result in the forceful expulsion of fecal material upon completion of examination.
    • Less commonly, older children with Hirschsprung disease may be chronically malnourished and/or present with Hirschsprung enterocolitis.

Causes

  • Genetic causes
    • The disease is generally sporadic, although incidence of familial disease has been increasing.
    • Multiple loci appear to be involved, including chromosomes 13q22, 21q22, and 10q.
    • Mutations in the Ret proto-oncogene have been associated with multiple endocrine neoplasia (MEN) 2A or MEN 2B and familial Hirschsprung disease.2,3
    • Other genes associated with Hirschsprung disease include the glial cell-derived neurotrophic factor gene, the endothelin-B receptor gene, and the endothelin-3 gene.
  • Associated conditions
    • Hirschsprung disease is strongly associated with Down syndrome; 5-15% of patients with Hirschsprung disease also have trisomy 21.
    • Other associations include Waardenburg syndrome, congenital deafness, malrotation, gastric diverticulum, and intestinal atresia.

More on Hirschsprung Disease

Overview: Hirschsprung Disease
Differential Diagnoses & Workup: Hirschsprung Disease
Treatment & Medication: Hirschsprung Disease
Follow-up: Hirschsprung Disease
Multimedia: Hirschsprung Disease
References
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References

  1. Meza-Valencia BE, de Lorimier AJ, Person DA. Hirschsprung disease in the U.S. associated Pacific Islands: more common than expected. Hawaii Med J. Apr 2005;64(4):96-8, 100-1. [Medline].

  2. Machens A, Hauptmann S, Dralle H. Modification of multiple endocrine neoplasia 2A phenotype by cell membrane proximity of RET mutations in exon 10. Endocr Relat Cancer. Oct 20 2008;[Medline].

  3. Edery P, Lyonnet S, Mulligan LM, et al. Mutations of the RET proto-oncogene in Hirschsprung's disease. Nature. Jan 27 1994;367(6461):378-80. [Medline].

  4. Emir H, Akman M, Sarimurat N, et al. Anorectal manometry during the neonatal period: its specificity in the diagnosis of Hirschsprung's disease. Eur J Pediatr Surg. Apr 1999;9(2):101-3. [Medline].

  5. Wildhaber BE, Pakarinen M, Rintala RJ, Coran AG, Teitelbaum DH. Posterior myotomy/myectomy for persistent stooling problems in Hirschsprung's disease. J Pediatr Surg. Jun 2004;39(6):920-6; discussion 920-6. [Medline].

  6. Minkes RK, Langer JC. A prospective study of botulinum toxin for internal anal sphincter hypertonicity in children with Hirschsprung's disease. J Pediatr Surg. Dec 2000;35(12):1733-6. [Medline].

  7. Belknap WM. Hirschsprung's Disease. Curr Treat Options Gastroenterol. Jun 2003;6(3):247-256. [Medline].

  8. Fujimoto T, Hata J, Yokoyama S, Mitomi T. A study of the extracellular matrix protein as the migration pathway of neural crest cells in the gut: analysis in human embryos with special reference to the pathogenesis of Hirschsprung's disease. J Pediatr Surg. Jun 1989;24(6):550-6. [Medline].

  9. Hackam DJ, Filler RM, Pearl RH. Enterocolitis after the surgical treatment of Hirschsprung's disease: risk factors and financial impact. J Pediatr Surg. Jun 1998;33(6):830-3. [Medline].

  10. Ikeda K, Goto S. Diagnosis and treatment of Hirschsprung's disease in Japan. An analysis of 1628 patients. Ann Surg. Apr 1984;199(4):400-5. [Medline].

  11. Kaplan P, de Chaderevian JP. Piebaldism-Waardenburg syndrome: histopathologic evidence for a neural crest syndrome. Am J Med Genet. Nov 1988;31(3):679-88. [Medline].

  12. Langer JC. Persistent obstructive symptoms after surgery for Hirschsprung's disease: development of a diagnostic and therapeutic algorithm. J Pediatr Surg. Oct 2004;39(10):1458-62. [Medline].

  13. Polley TZ, Coran, AG. Hirschsprung's disease in the newborn. Pediatric Surg. 1986;1:80-3.

  14. Puffenberger EG, Kauffman ER, Bolk S, et al. Identity-by-descent and association mapping of a recessive gene for Hirschsprung disease on human chromosome 13q22. Hum Mol Genet. Aug 1994;3(8):1217-25. [Medline].

  15. Reding R, de Ville de Goyet J, Gosseye S, et al. Hirschsprung's disease: a 20-year experience. J Pediatr Surg. Aug 1997;32(8):1221-5. [Medline].

  16. Roed-Petersen K, Erichsen G. The Danish pediatrician Harald Hirschsprung. Surg Gynecol Obstet. Feb 1988;166(2):181-5. [Medline].

  17. Swenson O, Sherman JO, Fisher JH. Diagnosis of congenital megacolon: An analysis of 501 patients. J Pediatr Surg. 1973;8:587-594. [Medline].

  18. Tiryaki T, Demirbag S, Atayurt H, Cetinkursun S. Topical nitric oxide treatment after pull through operations for Hirschsprung disease. J Pediatr Gastroenterol Nutr. Mar 2005;40(3):390-2. [Medline].

  19. Wartiovaara K, Salo M, Sariola H. Hirschsprung's disease genes and the development of the enteric nervous system. Ann Med. Feb 1998;30(1):66-74. [Medline].

  20. Yanchar NL, Soucy P. Long-term outcome after Hirschsprung's disease: patients' perspectives. J Pediatr Surg. Jul 1999;34(7):1152-60. [Medline].

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Further Reading

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Keywords

Hirschsprung disease, Hirschsprung's disease, Hirschsprung enterocolitis, Hirschsprung's enterocolitis, congenital aganglionosis, congenital megacolon, megacolon congenitum, Hirschsprung's disease, enterocolitis, abdominal distention, outflow incontinence, transmural intestinal necrosis, intestinal perforation, neonatal meconium plug syndrome, multiple endocrine neoplasia, MEN, Waardenburg syndrome, congenital deafness, malrotation, gastric diverticulum, intestinal atresia

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Contributor Information and Disclosures

Author

Holly L Neville, MD, Assistant Professor of Clinical Surgery, Division of Pediatric Surgery, University of Miami Miller School of Medicine
Holly L Neville, MD is a member of the following medical societies: American Academy of Pediatrics, American College of Surgeons, American Pediatric Surgical Association, and Association of Women Surgeons
Disclosure: Nothing to disclose.

Medical Editor

Hisham Nazer, MB, BCh, FRCP, DCh, DTM&H, Professor of Pediatrics, Consultant in Pediatric Gastroenterology, Hepatology and Clinical Nutrition, Bushnaq Medical Centre, University of Jordan
Hisham Nazer, MB, BCh, FRCP, DCh, DTM&H is a member of the following medical societies: Royal College of Paediatrics and Child Health, Royal College of Physicians, Royal College of Surgeons in Ireland, Royal College of Surgeons of Edinburgh, and Royal Society of Tropical Medicine and Hygiene
Disclosure: Nothing to disclose.

Pharmacy Editor

Mary L Windle, PharmD, Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy, Pharmacy Editor, eMedicine
Disclosure: Pfizer Inc Stock Investment from broker recommendation; Avanir Pharma Stock Investment from broker recommendation

CME Editor

Steven M Schwarz, MD, FAAP, FACN, AGAF, Professor of Pediatrics, State University of New York, Downstate Medical Center College of Medicine; Distinguished Lecturer, New York Medical College, School of Public Health
Steven M Schwarz, MD, FAAP, FACN, AGAF is a member of the following medical societies: American Academy of Pediatrics, American College of Nutrition, American College of Physician Executives, American Gastroenterological Association, American Pediatric Society, Gastroenterology Research Group, New York Academy of Medicine, North American Society for Pediatric Gastroenterology and Nutrition, and Society for Pediatric Research
Disclosure: TAP Pharmaceuticals Honoraria Speaking and teaching; Curemark, LLC Consulting fee Board membership

Chief Editor

Carmen Cuffari, MD, Associate Professor, Department of Pediatrics, Division of Gastroenterology/Nutrition, Johns Hopkins University School of Medicine
Carmen Cuffari, MD is a member of the following medical societies: American College of Gastroenterology, American Gastroenterological Association, North American Society for Pediatric Gastroenterology, Hepatology and Nutrition, and Royal College of Physicians and Surgeons of Canada
Disclosure: Nothing to disclose.

 
 
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