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Hirschsprung's Disease

Congenital Megacolon

Hirschsprung's disease (congenital megacolon, aganglionic megacolon) is characterized by an absence of ganglion cells in the colon resulting in a functional obstruction. It is named after the Danish physician Harold Hirschsprung.


Presentation

Most of the times the disease is diagnosed shortly after birth but in some patients it may be diagnosed later in childhood. The most common presenting features in infants include the following [9].

The clinical features in older children are:

Down Syndrome
  • RET acts as a modifier gene for the HSCR phenotype in patients with CCHS, BBS, and Down syndrome, but not in patients with MWS and WS4.[ncbi.nlm.nih.gov]
  • One of the children with Down's syndrome and total colonic aganglionosis died. Another had correction of a congenital heart disease, colostomy and is awaiting definitive surgery.[ncbi.nlm.nih.gov]
  • Down syndrome also predisposes to HSCR.[jci.org]
  • These findings plus the fact that 9% of these children were also diagnosed as having Down's Syndrome, were evidence that the aetiology of Hirschsprung's Disease may be partially genetic.[ncbi.nlm.nih.gov]
  • Down's Syndrome (3% of Down's syndrome have Hirschsprung's disease). Malrotation. Ileal and colonic atresias. Neurocristopathies (neuroblastoma, phaeochromocytoma, neurofibromatosis, Waardenberg's syndrome, and MEN IIA).[fetalultrasound.com]
Neonatal Intestinal Obstruction
  • HSCR (aganglionic megacolon) is a frequent diagnostic and clinical challenge in perinatology and pediatric surgery, and a major cause of neonatal intestinal obstruction.[ncbi.nlm.nih.gov]
  • Another rare cause of neonatal intestinal obstruction is the megacystis-microcolon-intestinal hypoperistalsis syndrome. 22 In this disorder, the small bowel is dilated and shortened, and the colon is a microcolon ( Figure 7 ) .[aafp.org]
  • "Failure to Pass Meconium: Diagnosing Neonatal Intestinal Obstruction". American Family Physician. 60 (7): 2043. ISSN 0002-838X. Martucciello G, Ceccherini I, Lerone M, Jasonni V (2000). "Pathogenesis of Hirschsprung's disease".[en.wikipedia.org]
Bradypnea
  • Soon after birth he started to show bradypnea, bradycardia and cyanosis, being submitted to tracheal intubation and started empiric antibiotic therapy for suspected early neonatal sepsis.[ncbi.nlm.nih.gov]
Constipation
  • However, constipation and soiling are still the main long-term complications.[ncbi.nlm.nih.gov]
  • Nine (36%) of patients in the case group required prolonged laxative use for constipation during the first year of life compared with 0 (0%) controls (P CONCLUSION: Neonatal constipation is associated with long-term GI-related disorders and should be[ncbi.nlm.nih.gov]
  • Abstract Adult Hirschsprung's disease (HD) is a rare motor disorder of the gut that is frequently misdiagnosed as refractory constipation.[ncbi.nlm.nih.gov]
  • A 24-year-old male patient presented with refractory constipation since childhood, and habituated to high-dose laxative combinations.[ncbi.nlm.nih.gov]
  • Since 3 years before her death, she had exhibited the feeling of abdominal distention, which was diagnosed as constipation. However, her constipation did not respond well to the prescribed oral administration of laxatives and enemas.[ncbi.nlm.nih.gov]
Diarrhea
  • Abstract We report the case of a 2-year-old boy with Hirschsprung's disease who developed perianal pseudoverrucous papules and nodules subsequent to persistent diarrhea and stool leakage after Giardia infection.[ncbi.nlm.nih.gov]
  • A 15-year-old female referred to Children's Medical Center with lethargy and low grade diarrhea. She had hypocalcemia and hypoalbuminemia with high PT and INR. Because of loss of conscious, she admitted at PICU.[ncbi.nlm.nih.gov]
  • Pouchitis were not found in the MLDP group, whereas 2 patients in the CLDP group (28.6%) presented with pouchitis and intractable diarrhea, requiring spur division.[ncbi.nlm.nih.gov]
  • HAEC and inflammatory bowel disease (IBD) have similar clinical presentation including diarrhea, hematochezia, and abdominal pain. In recent years, isolated cases of IBD have been reported in patients who had surgical treatment for HSCR.[ncbi.nlm.nih.gov]
  • During infancy the child has difficulty gaining weight, constipation, abdominal distension, episodes of diarrhea and vomiting.[childrens.memorialhermann.org]
Abdominal Distension
  • Clinical features of SV typically present with long-term constipation, severe abdominal pain, and progressive abdominal distension. The "coffee bean sign" could be observed in imaging examinations.[ncbi.nlm.nih.gov]
  • The child also developed abdominal distension on the second day of life with passage of scanty meconium. The diagnosis of Hirschsprung's disease (HD) was confirmed by histology. HD in association with right heterotaxy has not been reported earlier.[ncbi.nlm.nih.gov]
  • She developed severe intestinal obstruction and presented to the emergency department with significant abdominal distension. A computed tomographic scan confirmed significant fecal loading of the entire colon and rectum.[ncbi.nlm.nih.gov]
  • We report the case of a 2-week-old baby girl admitted to our clinic for abdominal distension and vomiting.[ncbi.nlm.nih.gov]
  • He had recurrent episodes of hypoglycemia, hyperglycemia, metabolic acidosis, abdominal distension, leukocytosis, increase in C-reactive protein levels, with negative blood cultures and suspected inborn error of metabolism.[ncbi.nlm.nih.gov]
Loss of Appetite
  • […] of appetite Cleveland Clinic is a non-profit academic medical center.[my.clevelandclinic.org]
  • In general, however, even children who don’t have early symptoms may experience: constipation that becomes worse with time loss of appetite delayed growth small, watery stools Diagnosing Hirschsprung disease Diagnosis begins with a thorough health history[mottchildren.org]
  • A person can experience extreme constipation, swelling of the abdomen, infections, and a loss of appetite over time. “They may also start vomiting," adds Dr. Ganjhu.[health.com]
Bilious Vomiting
  • A 2-day-old female was admitted with severe abdominal distention, bilious vomiting and failure to pass meconium. A distended abdomen accompanied by hypoactive bowel sounds was also observed.[ncbi.nlm.nih.gov]
  • Diagnosis Delay in passage of meconium, obstipation, abdominal distention, bilious vomiting, and failure to thrive may be symptoms of HD.[ipeg.org]
  • Bilious vomiting, with or without abdominal distention, is usually the first sign of small bowel obstruction.[aafp.org]
Cyanosis
  • Soon after birth he started to show bradypnea, bradycardia and cyanosis, being submitted to tracheal intubation and started empiric antibiotic therapy for suspected early neonatal sepsis.[ncbi.nlm.nih.gov]
Thrombosis
  • MTHFR C677T (methylenetetrahydrofolate) gene homozygote mutation was a risk factor for thrombosis.[ncbi.nlm.nih.gov]

Workup

The general physical examination of a child with Hirschsprung’s disease will show distended abdomen. Loops of bowel may be felt in the abdomen. There will be loss of muscle tone in the rectal muscles on rectal examination.
The investigations carried out to confirm the diagnosis include:

  • Plain abdominal X-ray: show distended bowel loops.
  • Barium enema: classic finding is narrowed distal colon with proximal dilatation.
  • Anorectal manometry: detects the absence of normal inhibitory reflexes in the rectum and anus.
  • Full thickness rectal biopsy: performed under general anesthesia and shows the absence of ganglion cells in the affected part.
  • Suction rectal biopsy: it is currently the gold standard test in the diagnosis of hirschsprung’s disease. It involves the immunohistochemical staining for acetylcholinesterase and calretinin.
Pneumoperitoneum
  • Rare manifestation of Hirschsprung's disease is spontaneous pneumoperitoneum which remains a surgical emergency. Delay in recognizing and treatment can significantly worsen prognosis.[ncbi.nlm.nih.gov]
  • Herein, we describe a unique case of a 2-day-old infant that presented with pneumoperitoneum, in which a perforated MD was induced by distal intestinal obstruction secondary to total colonic aganglionosis.[ncbi.nlm.nih.gov]

Treatment

The management of patients with Hirschsprung’s disease consists of supportive care and definitive treatment. Supportive or medical treatment is to treat general manifestations of the disease before definitive surgical treatment is performed and also to manage postoperative bowel function. It consists of:

  • Intravenous fluids to maintain fluid and electrolyte balance.
  • Nasogastric decompression.
  • Intravenous antibiotics both preoperatively and postoperatively.
  • Rectal and colonic lavage with a large caliber rectal tube [10].

Post operatively, antibiotics are given to prevent enterocolitis. If enterocolitis develops, then resuscitation along with antibiotics and mast cell stabilizer drugs are helpful. Injection of botulinum toxin within the contracted internal sphincter may help in inducing normal bowel movements in postoperative patients.

The definitive treatment for Hirschsprung’s disease is surgery. The affected part of the colon is resected and an end to end anastomosis is made between the normal bowel loops. There are a number of procedures to repair the aganglionic colon.

  • Swenson procedure: The affected segment is resected up to the sigmoid colon and an anastomosis is created between the normal colon and low rectum.
  • Duhamel procedure: The whole of the aganglionic bowel is resected and anastomosis is performed by bringing the proximal colon to the remaining rectum through the retro rectal space.
  • Soave (endorectal) procedure: In this technique, rectal mucosa and submucosa are resected and the normal bowel is pulled through the affected muscular cut off of the rectum.
  • Anorectal myomectomy: It is performed in case of extremely short segment disease.
  • Laproscopic approach: The unaffected bowel is joined with the rectal cut off after delivering the rectum and aganglionic bowel through the anus.
  • Transanal pull through procedures: This procedure in carried out through the anus without any intra-abdominal dissection.

Prognosis

Mortality rates in untreated Hirschsprung’s disease are approximately 80%. The prognosis of Hirschsprung’s disease is generally good after surgery. Some of the patients may develop complications like constipation, fecal incontinence or enterocolitis which may lead to mortality rates as high as 30%. Patients who suffer from an associated syndrome or have long-segment disease have a much poorer prognosis [7] [8].

Etiology

Hirschsprung’s disease is known to be caused by mutations in the RET-proto oncogene on chromosome 10q11.2. Family history of the disease is positive in about 30% of cases. In addition, there are several syndromes associated with the occurrence of Hirschsprung’s disease - the most common of which is Down syndrome. Other less common syndromes are Waardenburg-Shah syndrome, Goldburg-Shpritzen megacolon syndrome and congenital central hypoventilation syndrome.

Epidemiology

Hirschsprung’s disease is a congenital disorder that may be familial or acquired. The condition is more common among white males. The male to female ratio is 4.32:1. The disease affects 1 in 5400 to 7200 newborns in the United States annually. It is more common in Asian-Americans. According to international data, the annual incidence rate of the disease is estimated to be 1 case in around 1500 to 7000 newborns [1] [2]. The condition is found to be present in about 9% of patients with Down syndrome [3].

Sex distribution
Age distribution

Pathophysiology

The enteric nervous system supplying the intestines consists of submucosal (Meissner’s) plexus, myenteric (Auerbach’s) plexus and the smaller mucosal plexus. The absorption, secretion, motility and blood flow of the gut is under the control of enteric nervous system. The normal intestinal motility is under the control of the enteric ganglia. The intrinsic neurons cause relaxation of the intestinal smooth muscles while extrinsic neurons containing cholinergic and adrenergic fibers cause contraction and inhibition respectively.

In Hirschsprung’s disease, the myenteric and submucosal plexuses are absent and the control of intestinal smooth muscles is predominantly extrinsic. This leads to increased smooth muscle tone in the intestine which in turn causes uncoordinated peristalsis and functional obstruction.

The ganglions in the enteric nervous system are derived from the neural crest cells which migrate to the intestine during the twelfth week of development. One of the most accepted causes of aganglionosis in Hirschsprung’s disease is the failure of migration of the neural crest cells. In other cases, there might be apoptosis, failure of proliferation or improper differentiation of the neuroblasts despite their normal migration to the colon. Alternatively, there may be some dysfunction or absence of the factors like laminin, fibronectin, neural cell adhesion molecule and neurotropic factors, which are responsible for normal enteric ganglion development.

Genetic studies suggest that the most common gene mutation associated with Hirschsprung’s disease is the RET proto-oncogene [4] [5]. Overexpression of DVL1 and DVL3 gene has also been found to be present in Hirschsprung’s disease. In addition to mutation in the RET proto-oncogene, about 50% of the patients with this disorder have got mutations in several other genes; GDNF, GFR alpha1, NRTN, EDNRB, ET3, ZFHX1B, PHOX2b, SOX10 and SHH [6].

Prevention

There is no preventive measure against Hirschsprung disease as it is a developmental disorder.

Summary

Hirschsprung’s disease, also known as congenital aganglionic megacolon, is a developmental disorder characterized by inability of the distal colon to relax due to the failure of migration of neural crest cells into the colon to form the enteric nerve plexuses. There is absence of ganglion cells in the affected segment due to which the affected part of the colon remains contracted and the proximal segment becomes dilated. This results in functional intestinal obstruction.

About 90% of the patients are diagnosed in the new born period. Hirschsprung’s disease is suspected in any neonate who does not pass meconium within 24 to 48 hours of birth. The condition is diagnosed with barium enema and rectal biopsy and is treated by surgically removing the affected portion of intestine.

Patient Information

Hirschsprung’s disease is a congenital anomaly of the colon in which the normal peristaltic movements in a portion of gut are absent leading to functional obstruction of the intestine. The infants with this disease are unable to pass meconium after birth. Some patients may present in childhood with symptoms of chronic constipation, distended abdomen and malnutrition etc. if diagnosed timely, it is not a life threatening condition and is treated successfully by surgery.

References

Article

  1. Meza-Valencia BE, de Lorimier AJ, Person DA. Hirschsprung disease in the U.S. associated Pacific Islands: more common than expected. Hawaii medical journal. Apr 2005;64(4):96-98, 100-101.
  2. Russell MB, Russell CA, Niebuhr E. An epidemiological study of Hirschsprung's disease and additional anomalies. Acta paediatrica. Jan 1994;83(1):68-71.
  3. Pini Prato A, Rossi V, Mosconi M, et al. A prospective observational study of associated anomalies in Hirschsprung's disease. Orphanet journal of rare diseases. 2013;8:184.
  4. Leon TY, So MT, Lui VC, et al. Functional analyses of RET mutations in Chinese Hirschsprung disease patients. Birth defects research. Part A, Clinical and molecular teratology. Jan 2012;94(1):47-51.
  5. So MT, Leon TY, Cheng G, et al. RET mutational spectrum in Hirschsprung disease: evaluation of 601 Chinese patients. PloS one. 2011;6(12):e28986.
  6. Butler Tjaden NE, Trainor PA. The developmental etiology and pathogenesis of Hirschsprung disease. Translational research : the journal of laboratory and clinical medicine. Jul 2013;162(1):1-15.
  7. Hackam DJ, Reblock K, Barksdale EM, Redlinger R, Lynch J, Gaines BA. The influence of Down's syndrome on the management and outcome of children with Hirschsprung's disease. Journal of pediatric surgery. Jun 2003;38(6):946-949.
  8. Caniano DA, Teitelbaum DH, Qualman SJ. Management of Hirschsprung's disease in children with trisomy 21. American journal of surgery. Apr 1990;159(4):402-404.
  9. Vorobyov GI, Achkasov SI, Biryukov OM. Clinical features' diagnostics and treatment of Hirschsprung's disease in adults. Colorectal disease : the official journal of the Association of Coloproctology of Great Britain and Ireland. Dec 2010;12(12):1242-1248.
  10. Marty TL, Seo T, Sullivan JJ, Matlak ME, Black RE, Johnson DG. Rectal irrigations for the prevention of postoperative enterocolitis in Hirschsprung's disease. Journal of pediatric surgery. May 1995;30(5):652-654.

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Last updated: 2018-06-22 01:29