Synonyms: congenital aganglionosis, congenital megacolon, megacolon congenitum

Description

• 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.¹
• The result is clinical Hirschsprung's disease.
• Very rarely the small intestine may also be involved.

Epidemiology

• The incidence is around 1 in 5,000 births but it affects boys 4 times as often as girls.¹
• 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.

Genetics

• About 30% give a family history of the disease.
• 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.²
  • Another variation called Hirschsprung 2 is on chromosome 13.³
  • Hirschsprung modifier 1 is on chromosome 10.
  • There is short-segment disease due to problems on chromosome 3 and 19.^4,5
• There are many other variants also listed in OMIM.

Associated diseases

• There may be an association with multiple endocrine neoplasia of the MEN2A and MEN2B varieties.
• Between 5% and 15% of patients with Hirschsprung's disease may also have Down's syndrome.
• Other associations include Waardenburg's syndrome, congenital deafness, malrotation, gastric diverticulum, and intestinal atresia.
• There are 3 variations of Waardenburg's syndrome listed in OMIM.⁶ The major features are congenital deafness and partial albinism.

Presentation

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.

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, 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.

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.

Differential diagnosis

In the neonatal period the main alternative diagnosis with delayed passage of meconium is meconium ileus which suggests cystic fibrosis.

Investigations

• Raised white blood cell count - possibility of enterocolitis.
• Plain abdominal X-ray - looking for obstruction (usually a dilated lower bowel).
• Single-contrast barium enema - if there is no suspicion of perforation of the bowel, an unprepared single-contrast barium enema may demonstrate the transition from the normal-sized bowel to the dilated segment. The abnormally innervated segment is of normal size and it is the normal segment proximal to it that is dilated. Neonates may not have had time for this dilated normally innervated segment to have developed. The transition zone may be quite obvious in adult patients with untreated disease.⁷
• 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. It is also a very useful tool in the neonatal period but it is not a substitute for rectal biopsy.⁸
• 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 to 2½ cms 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.
• Detection of serum proteins - although at an early stage of research, the detection of serum proteins to aid early screening and diagnosis of Hirschsprung's disease looks promising.⁹

Management

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.
• Presence of enterocolitis - requires broad-spectrum antibiotics and aggressive intravenous rehydration.

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.
• The Swenson 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.¹⁰
• Surgery will also be dictated by success of decompression:
  • Unsuccessful preoperative decompression - a colostomy may be required whilst the dilated bowel returns to its normal size. This may be followed by a diverting colostomy and eventual closure.
  • Successful preoperative decompression - if there are no complications and dilatation has been adequately reversed by preoperative decompression, then a one-stage procedure may be performed but the pathologist is extremely important in this. Segments of abnormal bowel are sent for immediate histological analysis to ascertain if normal bowel has yet been reached. On the one hand the surgeon does not wish to excise more bowel than is necessary but, if he should leave behind an aganglionic segment, the condition will recur.

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 normal 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.¹¹ This would mean avoidance of surgery which has the risks of faecal incontinence.

Complications

Complications can include:

• Soiling and incontinence (<1%).¹
• Persisting constipation (~ 10%).¹
• Leakage of the anastomosis.
• Enterocolitis - postoperatively this may affect as many as a third.¹²
• Stricture of the resected segment - a late complication.
• Late intestinal obstruction - possibly due to adhesions.

Prognosis

• Most children acquire faecal continence and normal bowel habits but it does tend to be poorer than in normal controls.¹³ However, some children may not acquire full faecal continence until late adolescence and the psychological affects of this should not be underestimated.¹⁴ Unsurprisingly, acquirement of faecal continence is associated with an improvement in quality of life.¹⁵
• A recent study has 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.¹⁶
• The prognosis with Down's syndrome is less favourable and some people recommend permanent colostomy.

History

• 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 corpse.
• 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.

Document references

1. Kessmann J; Hirschsprung's disease: diagnosis and management. Am Fam Physician. 2006 Oct 15;74(8):1319-22. [abstract]
2. Hirschsprung disease; HSCR1, Online Mendelian Inheritance in Man (OMIM)
3. Hirschsprung disease; HSCR2, Online Mendelian Inheritance in Man (OMIM)
4. Hirschsprung disease; HSCR6, Online Mendelian Inheritance in Man (OMIM)
5. Hirschsprung disease; HSCR7, Online Mendelian Inheritance in Man (OMIM)
6. Waardenburg syndrome, Online Mendelian Inheritance in Man (OMIM).
7. Mindelzun RE, Hicks SM; Adult Hirschprung disease: radiographic findings. Radiology. 1986 Sep;160(3):623-5. [abstract]
8. 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. 1999 Apr;9(2):101-3. [abstract]
9. Wang JX, Qin P, Liu QL, et al; Detection and significance of serum protein marker of Hirschsprung disease. Pediatrics. 2007 Jul;120(1):e56-60. Epub 2007 Jun 4. [abstract]
10. Swenson O; Hirschsprung's disease: a review. Pediatrics. 2002 May;109(5):914-8.
11. Gershon MD; Transplanting the enteric nervous system: a step closer to treatment for aganglionosis. Gut. 2007 Apr;56(4):459-61.
12. Hackam DJ, Filler RM, Pearl RH; Enterocolitis after the surgical treatment of Hirschsprung's disease: risk factors and financial impact. J Pediatr Surg. 1998 Jun;33(6):830-3. [abstract]
13. Reding R, de Ville de Goyet J, Gosseye S, et al; Hirschsprung's disease: a 20-year experience. J Pediatr Surg. 1997 Aug;32(8):1221-5. [abstract]
14. Yanchar NL, Soucy P; Long-term outcome after Hirschsprung's disease: patients' perspectives. J Pediatr Surg. 1999 Jul;34(7):1152-60. [abstract]
15. 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 Feb;119(2):e374-83. [abstract]
16. 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 Jul;194(1):40-7. [abstract]

Internet and further reading

• Surgical Tutor; Hirschsprung's Disease 2010
• National Digestive Diseases Information Clearinghouse; What I need to know about Hirschsprung's disease

Acknowledgements