Hirschsprung's Disease

Authored by Dr Laurence Knott, 16 Jun 2014

Reviewed by:
Prof Cathy Jackson, 16 Jun 2014

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Synonyms: congenital aganglionosis, congenital megacolon, megacolon congenitum

  • The underlying pathology is an absence of parasympathetic ganglion cells in the myenteric and submucosal plexus of the rectum, possibly extending to the colon.
  • Ganglion cells are derived from the neural crest and migrate caudally with the vagal nerve fibres along the intestine. They arrive in the proximal colon by 8 weeks of gestation and in the rectum by 12 weeks.
  • Arrest in migration leads to an aganglionic segment which is unable to relax, leading to a functional colonic obstruction.
  • The result is clinical Hirschsprung's disease.
  • The small intestine may also (very rarely) be involved.
  • A study in the North of England found a live birth prevalence of 1.65 per 10,000 live births. The male to female ratio was 2:1[2].
  • At least half of all cases are diagnosed in the first year of life and, by the age of 2, most have been diagnosed.
  • There are a few in whom diagnosis is delayed until later childhood or even adulthood.
  • Online Mendelian Inheritance in Man (OMIM) lists a number of different gene sites for Hirschsprung's disease:
    • One is on the X chromosome and could help to explain the male preponderance[3].
    • Another variation called Hirschsprung 2 is on chromosome 13[4].
    • Hirschsprung modifier 1 is on chromosome 10.
    • There is short-segment disease due to problems on chromosome 3 and 19[5, 6].
  • There are many other variants also listed in OMIM.
  • There may be an association with multiple endocrine neoplasia of the MEN2A and MEN2B varieties[7].
  • One study found that 15% of patients with Hirschsprung's disease also had Down's syndrome[8].
  • Other associations include Waardenburg's syndrome, congenital deafness, malrotation, gastric diverticulum, and intestinal atresia[9].
  • There are three variations of Waardenburg's syndrome listed in OMIM[10]. The major features are congenital deafness and partial albinism.

History

Neonatal period

  • Abdominal distention, failure of passage of meconium within the first 48 hours of life and repeated vomiting.
  • Delayed passage of meconium is very important, as nearly half of all infants with Hirschsprung's disease do not pass meconium within 36 hours and nearly half of infants with delayed first passage of meconium have Hirschsprung's disease.
Clinical Editor's notes (July 2017)
Dr Hayley Willacy draws your attention to this recent paper from the Archives of Disease in Childhood reporting that a quarter of infants with Hirschsprung's disease pass meconium within 24 hours of birth and nearly half within 48 hours of birth, limiting the validity of timing of first meconium as a screening question for Hirschsprung's disease[11] . In addition, one in three infants with Hirschsprung's disease is discharged home after birth, prior to diagnosis, placing a heavy burden on primary care to ensure timely referral.

Older infants and children

  • These present with chronic constipation that is resistant to the usual treatments and a daily enema may be required.
  • Rarely, they have soiling and overflow incontinence.
  • This is in contrast to children with functional constipation.
  • The disease causes early satiety, abdominal discomfort and distension due to the constipation and this leads to poor nutrition and poor weight gain.

Enterocolitis

  • This can develop at any age.
  • There is typically abdominal pain, fever, and foul-smelling and possibly bloody diarrhoea, with vomiting.
  • If not recognised early, this may progress to sepsis, transmural intestinal necrosis and perforation.
  • The mortality with this condition is around 30-35% and this accounts for most of the mortality associated with Hirschsprung's disease.
  • Hirschsprung patients who develop enterocolitis have a different mix of enteral organisms than those who do not[12].

Examination

Neonatal period

  • They may have abdominal distention (which is tympanic on percussion) and symptoms of intestinal obstruction.
  • They may present with acute enterocolitis in this age group and (rarely) with neonatal meconium plug syndrome or appendicitis.

Older infants and children

  • They have chronic constipation.
  • There may be marked abdominal distention with palpable dilated loops of colon.
  • Rectal examination often reveals an empty rectum and may result in the forceful expulsion of faecal material as examination is completed.
  • More rarely, older children can present with malnourishment and possibly enterocolitis.

In the neonatal period the main alternative diagnosis with delayed passage of meconium is meconium ileus which suggests cystic fibrosis. In older patients, other causes of chronic constipation and intestinal obstruction should be considered[13].

  • Raised white blood cell count - possibility of enterocolitis.
  • Imaging - plain abdominal X-ray may show obstruction (usually a dilated lower bowel). Contrast imaging may be normal in the first three months of life and in patients with total colon involvement[14]. Double-contrast barium enema may show a markedly dilated proximal colonic segment with a transition zone and a narrowed distal colonic segment. Similar findings may be demonstrated by CT scanning. These appearances in an adult with chronic constipation should suggest a diagnosis of Hirschsprung's disease[15].
  • Anorectal manometry - in older children with chronic constipation and an atypical history for either Hirschsprung's disease or functional constipation, anorectal manometry can be helpful in making or excluding the diagnosis. In Hirschsprung's disease there is failure of reflex relaxation of the internal anal sphincter in response to inflation of a rectal balloon. One study found that anorectal manometry was a more accurate diagnostic tool than barium enema[16]. It should not, however, replace rectal suction biopsy[17].
  • Rectal biopsy - the definitive diagnosis rests on histology of a rectal biopsy. Tissue is obtained either by suction anal biopsy or by transanal wedge resection. Suction biopsy is best performed 2-2.5 cm above the dentate line, on the posterior wall to reduce the risk of perforation. The specimen is examined for the presence or absence of ganglion cells in the myenteric plexus. This may be difficult in short segments or with skip lesions and acetylcholine staining may be helpful[9].
  • Detection of serum proteins - the detection of serum proteins to aid early screening and diagnosis of Hirschsprung's disease looks promising[18].

Acute problems

  • Presence of intestinal obstruction - intravenous rehydration, gastric and intestinal decompression and cessation of oral feeding are required. Decompression may be achieved by a nasogastric tube from above and digital rectal examination or normal saline enemas once or twice a day from below[19, 20].
  • Presence of enterocolitis - requires broad-spectrum antibiotics and aggressive intravenous rehydration[21].

Surgical options

  • The surgical options are limited by the patient's age, mental status, ability to perform activities of daily living, length of the aganglionic segment, degree of colonic dilation, and any enterocolitis.
  • Swenson's procedure was the original procedure performed for Hirschsprung's disease.  It involves releasing the defective distal colon to just above the anal canal and performing an end-to-end anastomosis. Thus, the aganglionic segment is removed[22].
  • More recently, a transanal approach has been used. A full-thickness incision is made on the rectal wall posteriorly, 0.5 cm above the dentate line. The mobilised segment is resected about 5 cm above the transition zone. Frozen sections are performed whenever the transition zone is not clearly seen intra-operatively. The operation is completed by full thickness colo-anal anastomosis[23].
  • Various modifications concerning the length of the dissected rectum and the shape and length of the anastamosis continue to be developed[24].

No special diet is required in patients with Hirschsprung's disease (unless they have acute obstruction or enterocolitis) and correction of the defect usually results in a normally functioning gastrointestinal tract.

Future therapy

There is some hope that the use of autologous neural crest-derived enteric stem cells may be a treatment for Hirschsprung's disease. This would mean avoidance of surgery which has the risks of faecal incontinence[25].

Complications can include:

  • Soiling and incontinence (<1%)[14].
  • Persisting constipation (~ 10%)[14].
  • Leakage of the anastomosis.
  • Enterocolitis - one study reported an incidence of 12%[26].
  • Stricture of the resected segment - a late complication.
  • Late intestinal obstruction - possibly due to adhesions.
  • Most children acquire faecal continence and normal bowel habits but a number of older children still have ongoing continence problems[27]. Unsurprisingly, acquirement of faecal continence is associated with an improvement in quality of life[28].
  • A study followed over 300 patients after surgery for Hirschsprung's disease, over 8-20 years. Although satisfactory results were achieved in most, some continued to have abnormal colonic motility and problems with the internal anal sphincter[29].
  • The prognosis with Down's syndrome is less favourable and some people recommend permanent colostomy.
  • The first report of a patient with Hirschsprung's disease was made in 1691 by Frederik Ruysch. He was a Dutch anatomist and botanist who lived from 1638 to 1731. He studied medicine in Leiden and was awarded MD in 1664. He had a passion for anatomy and would ask grave diggers to open graves so that he could study the corpses.
  • Harald Hirschsprung was a Danish paediatrician who was born in 1830 and died in 1916. His father founded a tobacco factory but he refused to join the business. He published the classical description of congenital megacolon in 1886.

Further reading and references

  1. Burkardt DD, Graham JM Jr, Short SS, et al; Advances in Hirschsprung disease genetics and treatment strategies: an update for the primary care pediatrician. Clin Pediatr (Phila). 2014 Jan53(1):71-81. doi: 10.1177/0009922813500846. Epub 2013 Sep 3.

  2. Best KE, Glinianaia SV, Bythell M, et al; Hirschsprung's disease in the North of England: prevalence, associated anomalies, and survival. Birth Defects Res A Clin Mol Teratol. 2012 Jun94(6):477-80. doi: 10.1002/bdra.23016. Epub 2012 Apr 18.

  3. Hirschsprung disease, HSCR1; Online Mendelian Inheritance in Man (OMIM)

  4. Hirschsprung disease, HSCR2; Online Mendelian Inheritance in Man (OMIM)

  5. Hirschsprung disease, HSCR6; Online Mendelian Inheritance in Man (OMIM)

  6. Hirschsprung disease, HSCR7; Online Mendelian Inheritance in Man (OMIM)

  7. Moore SW, Zaahl MG; Multiple endocrine neoplasia syndromes, children, Hirschsprung's disease and RET. Pediatr Surg Int. 2008 May24(5):521-30. doi: 10.1007/s00383-008-2137-5. Epub 2008 Mar 26.

  8. Menezes M, Puri P; Long-term clinical outcome in patients with Hirschsprung's disease and associated Down's syndrome. J Pediatr Surg. 2005 May40(5):810-2.

  9. Parisi M; Hirschsprung Disease Overview, Gene Reviews, 2011.

  10. Waardenburg Syndrome - Type 4A, WS4A; Online Mendelian Inheritance in Man (OMIM)

  11. Bradnock TJ, Knight M, Kenny S, et al; Hirschsprung's disease in the UK and Ireland: incidence and anomalies. Arch Dis Child. 2017 Aug102(8):722-727. doi: 10.1136/archdischild-2016-311872. Epub 2017 Mar 9.

  12. Yan Z, Poroyko V, Gu S, et al; Characterization of the intestinal microbiome of Hirschsprung's disease with and without enterocolitis. Biochem Biophys Res Commun. 2014 Mar 7445(2):269-74. doi: 10.1016/j.bbrc.2014.01.104. Epub 2014 Feb 10.

  13. Khan AR, Vujanic GM, Huddart S; The constipated child: how likely is Hirschsprung's disease? Pediatr Surg Int. 2003 Aug19(6):439-42. Epub 2003 Apr 16.

  14. Kessmann J; Hirschsprung's disease: diagnosis and management. Am Fam Physician. 2006 Oct 1574(8):1319-22.

  15. Kim HJ, Kim AY, Lee CW, et al; Hirschsprung disease and hypoganglionosis in adults: radiologic findings and differentiation. Radiology. 2008 May247(2):428-34. doi: 10.1148/radiol.2472070182.

  16. Huang Y, Zheng S, Xiao X; Preliminary evaluation of anorectal manometry in diagnosing Hirschsprung's disease in neonates. Pediatr Surg Int. 2009 Jan25(1):41-5. doi: 10.1007/s00383-008-2293-7. Epub 2008 Nov 28.

  17. De Lorijn F, Reitsma JB, Voskuijl WP, et al; Diagnosis of Hirschsprung's disease: a prospective, comparative accuracy study of common tests. J Pediatr. 2005 Jun146(6):787-92.

  18. Zhang SC, Chen F, Jiang KL, et al; Comparative proteomic profiles of the normal and aganglionic hindgut in human Hirschsprung disease. Pediatr Res. 2014 Jun75(6):754-61. doi: 10.1038/pr.2014.33. Epub 2014 Apr 7.

  19. Juang D, Snyder CL; Neonatal bowel obstruction. Surg Clin North Am. 2012 Jun92(3):685-711, ix-x. doi: 10.1016/j.suc.2012.03.008. Epub 2012 Apr 17.

  20. Pashankar DS; Childhood constipation: evaluation and management. Clin Colon Rectal Surg. 2005 May18(2):120-7. doi: 10.1055/s-2005-870894.

  21. Demehri FR, Halaweish IF, Coran AG, et al; Hirschsprung-associated enterocolitis: pathogenesis, treatment and prevention. Pediatr Surg Int. 2013 Sep29(9):873-81. doi: 10.1007/s00383-013-3353-1.

  22. Swenson O; Hirschsprung's disease: a review. Pediatrics. 2002 May109(5):914-8.

  23. Mahajan JK, Rathod KK, Bawa M, et al; Transanal Swenson's operation for recto-sigmoid Hirschsprung's disease. Afr J Paediatr Surg. 2011 Sep-Dec8(3):301-5. doi: 10.4103/0189-6725.91678.

  24. Yang L, Tang ST, Cao GQ, et al; Transanal endorectal pull-through for Hirschsprung's disease using long cuff dissection and short V-shaped partially resected cuff anastomosis: early and late outcomes. Pediatr Surg Int. 2012 May28(5):515-21. doi: 10.1007/s00383-012-3071-0. Epub 2012 Mar 20.

  25. Hagl CI, Heumuller S, Klotz M, et al; Smooth muscle proteins from Hirschsprung's disease facilitates stem cell differentiation. Pediatr Surg Int. 2012 Feb28(2):135-42. doi: 10.1007/s00383-011-3010-5.

  26. Singh R, Cameron BH, Walton JM, et al; Postoperative Hirschsprung's enterocolitis after minimally invasive Swenson's procedure. J Pediatr Surg. 2007 May42(5):885-9.

  27. Mills JL, Konkin DE, Milner R, et al; Long-term bowel function and quality of life in children with Hirschsprung's disease. J Pediatr Surg. 2008 May43(5):899-905. doi: 10.1016/j.jpedsurg.2007.12.038.

  28. Hartman EE, Oort FJ, Aronson DC, et al; Explaining change in quality of life of children and adolescents with anorectal malformations or Hirschsprung disease. Pediatrics. 2007 Feb119(2):e374-83.

  29. Zhang SC, Bai YZ, Wang W, et al; Long-term outcome, colonic motility, and sphincter performance after Swenson's procedure for Hirschsprung's disease: a single-center 2-decade experience with 346 cases. Am J Surg. 2007 Jul194(1):40-7.

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