Introduction
Background
The first report of a patient with Hirschsprung disease (HD) was made in 1691 by Frederick Ruysch, but it was Danish pediatrician Harald Hirschsprung who in 1888 published the classic description of congenital megacolon.1 HD is characterized by the absence of myenteric and submucosal ganglion cells (Auerbach and Meissner plexuses) along a variable length of the distal alimentary tract. The disease results in decreased motility in the affected bowel segment, lack of propagation of peristaltic waves into the aganglionic colon, and abnormal or absent relaxation of this segment and of the internal anal sphincter.
Hirschsprung disease. Frontal abdominal radiograph showing marked dilatation of the bowel with no gas in the rectum.
Hirschsprung disease. Lateral view from a barium enema examination depicting the reduced diameter of the rectum and sigmoid.
Hirschsprung disease. Barium enema showing reduced caliber of the rectum, followed by a transition zone to an enlarged-caliber sigmoid.
Pathophysiology
The congenital absence of ganglion cells in the distal alimentary tract is the pathologic sine qua non of Hirschsprung disease (HD). The aganglionosis present in HD results from a failure of cells derived from the neural crest to populate the embryonic colon during development. This failure results from a fundamental defect in the microenvironment of the bowel wall that prevents ingrowth of neuroblasts. So far, 10 specific genetic defects are known to be associated with HD, including mutations to the endothelin-B receptor gene (EDNRB) and to receptor tyrosine kinase (RET). RET plays a key role in HD genesis, and multiple genes may be required to modulate clinical expression. Because of the polygenic nature the disease, the penetrance of the condition is variable, leading to the variable manifestations of HD.2,3,4
Frequency
International
The incidence of Hirschsprung disease is approximately 1 case per 5,000 live births.3
Mortality/Morbidity
The polygenic nature and varied penetrance of Hirschsprung disease (HD) determine a wide range of clinical symptoms. These include obstipation immediately after birth, as well as a milder picture associated with incomplete evacuation that eventually leads to a distended abdomen, recurrent constipation, and a high diaphragm.
Better diagnostic procedures, an emphasis on early diagnosis, and improvements in surgical techniques have contributed to decreased mortality rates in individuals with HD.
The greatest morbidity and mortality is observed in children younger than 1 year of age, as a result of possible Hirschsprung-associated enterocolitis (HAEC). The mean incidence is 25%.5 HAEC can be fatal if it is not rapidly diagnosed and treated.
Race
Hirschsprung disease (HD) is estimated to occur at a rate of 1 case per 5,000 live births; however, significant variance among ethnic groups seems to exist. For example, the rate is 1 case per 10,000 live births in Hispanics; 1.5 cases per 10,000 live births in whites; 2.1 cases per 10,000 live births in African-Americans; and 2.8 cases per 10,000 live births in Asian-Americans.
Sex
The ratio of males to females affected by Hirschsprung disease (HD) is 4:1. Interestingly, the male preponderance for the disease is reduced (1.2-1.9:1) when only patients with long-segment HD are considered.
Age
As a congenital disorder, Hirschsprung disease (HD) is manifested mostly within the first several weeks of life, and it is diagnosed in persons aged 5 years or younger. Occasionally, HD is diagnosed during adulthood.
Anatomy
Hirschsprung disease (HD) is regarded as a neurocristopathy, because it involves a premature arrest of the craniocaudal migration of vagal neural crest cells in the hindgut (at weeks 5-12 of gestation) to form the enteric nervous system. As a consequence, intramural ganglion cells in the Meissner and Auerbach plexuses are absent. The anus is always involved, and a variable length of distal intestine may be involved as well. The aganglionic, aperistaltic bowel segment effectively prevents the propulsion of the fecal stream, resulting in dilation and hypertrophy of the normal proximal colon.
HD can be classified by the extension of the aganglionosis, as follows:
- Classic HD - 75-80% of cases
- The aganglionic segment does not extend beyond the upper sigmoid.
- Long-segment HD - 20% of cases
- Total colonic aganglionosis - 3-8% of cases
Some rare variants include the following:
- Total intestinal aganglionosis - Involves the entire bowel
- Ultra–short-segment HD - Involves the distal rectum below the pelvic floor and the anus
Presentation
Newborns with Hirschsprung disease (HD) come to medical attention with the following symptoms:
- Failure to pass meconium within the first 24 hours of life (>90% of patients with HD)
- Abdominal distension that is relieved by rectal stimulation or enemas
- Vomiting
- Neonatal enterocolitis
Symptoms in older children and adults include the following:
- Severe constipation
- Abdominal distension
- Bilious vomiting
- Failure to thrive
Children presenting with abdominal distension, explosive diarrhea, vomiting, fever, lethargy, rectal bleeding, or shock may possibly have HAEC. The risk for HAEC is greatest before HD is diagnosed or after the definitive pull-through operation.6 Also, children with Down syndrome have an increased risk for HAEC.
HD occurs as an isolated trait in 70% of patients; it is associated with a chromosomal abnormality in 12% of cases (>90% of which involve trisomy 21) and with additional congenital anomalies (gastrointestinal malformation, cleft palate, polydactyly, cardiac septal defects, and craniofacial anomalies) in 18% of cases.
Some associated syndromes include the following:
- Down syndrome
- Multiple endocrine neoplasia type 2 (MEN2)
- Cat's-eye syndrome
- Waardenburg syndrome
- Bardet-Biedl syndrome
Preferred Examination
A diagnostic evaluation should begin with plain abdominal radiography followed by a contrast enema examination of the colon to confirm the diagnosis of Hirschsprung disease (HD).7,8 Occasionally, ultrasonographic findings may also suggest the diagnosis.
Manometry
Rectal manometry is complementary to contrast enema examination. Its sensitivity and specificity on systematic review are excellent, being 91% and 93%, respectively; the modality has an accuracy of 75%. Rectal manometry shows an absence of normal relaxation of the internal sphincter (rectal inhibitory reflex) and the reduction in the intraluminal pressure in the anal canal when the rectum is distended with a balloon. This technique is more reliable from day 12 after birth, when the normal recto-enteric reflex is present.
Biopsy
If ganglion cells are present, the predictive value of the biopsy in excluding HD is essentially 100%. A rectal suction biopsy or a full-thickness rectal biopsy can be performed. The first procedure eliminates the need for general anesthesia; however, the latter provides bigger fragments of the submucosal neural plexus for histologic examination.
In HD, the biopsy reveals an absence of ganglion cells, hypertrophy and hyperplasia of nerve fibers, and an increase in acetylcholinesterase-positive nerve fibers in the lamina propria and the muscularis mucosa. Samples must be obtained well above the anal valves, because ganglion cells are normally absent in the anal canal.
Limitations of Techniques
A radiologic or ultrasonographic study alone is not a sensitive enough to exclude Hirschsprung disease (HD). Manometry and/or rectal mucosal biopsy are required for accurate diagnosis.8
Differential Diagnoses
Constipation
Meconium Ileus
Meconium Plug Syndrome
Small Left Colon Syndrome
Other Problems to Be Considered
Intestinal neuronal dysplasia
More on Hirschsprung Disease |
 Overview: Hirschsprung Disease |
| Imaging: Hirschsprung Disease |
| Follow-up: Hirschsprung Disease |
| Multimedia: Hirschsprung Disease |
| References |
| Further Reading |
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References
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Further Reading
Evaluation and treatment of constipation in infants and children: recommendations of the North American Society for Pediatric Gastroenterology, Hepatology and Nutrition. North American Society for Pediatric Gastroenterology, Hepatology, and Nutrition. 1999 Nov (revised 2006 Sep). 13 pages. NGC:005245
ASGE guideline: guideline on the use of endoscopy in the management of constipation. American Society for Gastrointestinal Endoscopy. 2005 Aug. 3 pages. NGC:004485
Keywords
Hirschsprung disease, congenital megacolon, aganglionic megacolon, aganglionosis, HD, Hirschsprung's disease, transition zone, Swenson procedure, Soave pull-through procedure, Duhamel procedure, Hirschsprung-associated enterocolitis, Hirschsprung's-associated enterocolitis, HAEC, neurocristopathy
