eMedicine Specialties > Radiology > Pediatrics

Hirschsprung Disease

Ciro Yoshida, Jr, MD, Staff Physician, Department of Diagnostic Imaging, Federal University of São Paulo (UNIFESP)
Salomao Faintuch, MD, Clinical Fellow, Department of Vascular and Interventional Radiology, Beth Israel Deaconess Medical Center; Henrique M Lederman, MD, PhD, Consulting Staff, Department of Radiology, LeBonheur Children's Medical Center and St Jude Children's Research Hospital; Professor of Radiology and Pediatric Radiology, Chief, Division of Diagnostic Imaging in Pediatrics, Federal University of Sao Paulo, Brazil

Updated: Sep 17, 2008

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

Radiography

Findings

Hirschsprung disease. Frontal abdominal radiograph showing marked dilatation of the bowel with no gas in the rectum. In the sitting position, air-fluid levels in the large bowel are seen.

Hirschsprung disease. Lateral abdominal radiograph shows a very enlarged, stool-filled sigmoid. No air or stool content is seen in the rectum.

Hirschsprung disease. Lateral view from a barium enema examination depicting the reduced diameter of the rectum and sigmoid.

Hirschsprung disease. A 24-hour-delayed radiograph obtained after a barium enema examination shows retention of barium and stool in the rectum. This is associated with a dilated stool-filled sigmoid.

Hirschsprung disease. Barium enema showing reduced caliber and length of the large bowel, with no clear transition zone (total colonic aganglionosis).

Hirschsprung disease (HD) is more definitively diagnosed by means of contrast enema examination, which can show the presence of a transition zone, irregular contractions, mucosal irregularity, and delayed evacuation of contrast material, among other findings.⁸

Transition zone is the term applied to the region in which a marked change in caliber occurs, with the dilated, normal colon above and the narrowed, aganglionic colon below; although this is a highly reliable sign of HD, failure to visualize a transition zone does not rule out the presence of the disease.⁹

The hallmark of the diagnosis is demonstration of the transition zone from the dilated bowel to the reduced-caliber bowel. Obviously, finding more than 1 sign increases the accuracy in diagnosis. Signs of HD after barium enema administration include the following:

• Transition zone (often subtle during the first week of life)
• Abnormal, irregular contractions of aganglionic segment (rare)
• Thickening and nodularity of colonic mucosa proximal to transition zone (rare)
• Delayed evacuation of barium
• Mixed barium-stool pattern on delayed radiographs
• Distended bowel loops on plain radiographs that almost fill after contrast enema
• Question mark–shaped colon in total colonic aganglionosis

Degree of Confidence

Contrast enema examination is not as sensitive or reliable as rectal suction biopsy in ruling out Hirschsprung disease (HD).¹¹ It has a sensitivity and specificity of 70% and 83%, respectively.

False Positives/Negatives

The false-negative rate of barium enema examination is about 24%. The presence of a transition zone on barium enema examination is falsely positive in 42-48.5% of children with suspected Hirschsprung disease (HD).⁷  

Computed Tomography

Findings

A CT scan is not normally indicated.

Magnetic Resonance Imaging

Findings

An MRI scan is not normally indicated.

Ultrasonography

Findings

Although ultrasonography is not the first imaging tool for diagnosing Hirschsprung disease (HD), diagnosis is possible with real-time ultrasonography.¹² Oestreich reported a case of unsuspected HD in a 1-month-old baby who was taken to a pediatrician for a check-up.¹³ A distended abdomen was noted.¹³ Ultrasonography revealed the same pattern that is observed in a barium enema examination, that is, a dilated sigmoid narrowing to a narrow rectum.

Ultrasonography may also help in determining the dynamic or adynamic state of fluid-filled or solid-filled bowel loops.

Degree of Confidence

The degree of confidence is low, because gas-filled bowel loops can complicate the diagnosis.

Intervention

The treatment for Hirschsprung disease (HD) is surgical and is based on the removal or bypass of the poorly functioning, aganglionic bowel, with anastomosis of normally innervated intestine to the distal rectum. This can be performed by means of a preliminary colostomy followed by a definitive pull-through procedure or an immediate definitive procedure.⁵ Examples of the latter include the Swenson procedure, the Soave pull-through procedure, and the Duhamel procedure. Treatment innovations are the transanal endorectal pull-through and the laparoscopic approach to the 3 techniques.^6,14

In general, the treatment plan varies according to the extent of aganglionosis and the age of the patient. A 1-stage procedure is possible when diagnosis is made early, before colonic dilatation, in short-segment disease. Otherwise, a primary colostomy is required. For long-segment disease and total colonic aganglionosis, temporary enterostomy is often the first step in management before definitive surgery. In most cases, treatment restores nearly normal motility and enables most affected individuals to have normal bowel function.

Multimedia

Media file 1: Hirschsprung disease. Frontal abdominal radiograph showing marked dilatation of the bowel with no gas in the rectum.

Media file 2: Hirschsprung disease. Frontal abdominal radiograph showing marked dilatation of the small bowel with no gas in the rectum.

Media file 3: Hirschsprung disease. Frontal abdominal radiograph showing marked dilatation of the bowel with no gas in the rectum. In the sitting position, air-fluid levels in the large bowel are seen.

Media file 4: Hirschsprung disease. Lateral abdominal radiograph shows a very enlarged, stool-filled sigmoid. No air or stool content is seen in the rectum.

Media file 5: Hirschsprung disease. Barium enema technique shows slow contrast-material infusion.

Media file 6: Hirschsprung disease. Lateral view from a barium enema examination depicting the reduced diameter of the rectum and sigmoid.

Media file 7: Hirschsprung disease. Barium enema showing reduced caliber of the rectum, followed by a transition zone to an enlarged-caliber sigmoid.

Media file 8: Hirschsprung disease. Barium enema showing reduced caliber of the rectum, followed by a transition zone to an enlarged-caliber sigmoid.

Media file 9: Hirschsprung disease. A 24-hour-delayed radiograph obtained after a barium enema examination shows retention of barium and stool in the rectum. This is associated with a dilated stool-filled sigmoid.

Media file 10: Hirschsprung disease. Barium enema showing reduced caliber and length of the large bowel, with no clear transition zone (total colonic aganglionosis).

Media file 11: Hirschsprung disease. Barium enema showing a reduced-caliber rectum and dilated large-bowel loops with an irregular mucosal contour (dyskinesia).

Media file 12: Hirschsprung disease. Plain abdominal radiograph showing dilatation of the transverse colon and mucosal edema (toxic megacolon).

References

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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 

Contributor Information and Disclosures

Author

Ciro Yoshida, Jr, MD, Staff Physician, Department of Diagnostic Imaging, Federal University of São Paulo (UNIFESP)
Disclosure: Nothing to disclose.

Coauthor(s)

Salomao Faintuch, MD, Clinical Fellow, Department of Vascular and Interventional Radiology, Beth Israel Deaconess Medical Center
Salomao Faintuch, MD is a member of the following medical societies: American Roentgen Ray Society, Radiological Society of North America, and Society of Cardiovascular and Interventional Radiology
Disclosure: Nothing to disclose.

Henrique M Lederman, MD, PhD, Consulting Staff, Department of Radiology, LeBonheur Children's Medical Center and St Jude Children's Research Hospital; Professor of Radiology and Pediatric Radiology, Chief, Division of Diagnostic Imaging in Pediatrics, Federal University of Sao Paulo, Brazil
Henrique M Lederman, MD, PhD is a member of the following medical societies: Society for Pediatric Radiology
Disclosure: Nothing to disclose.

Medical Editor

Robert J Starshak, MD, Medical Director, Assistant Clinical Professor, Department of Radiology, Medical College of Wisconsin, Falls Medical Group
Disclosure: Nothing to disclose.

Pharmacy Editor

Bernard D Coombs, MB, ChB, PhD, Consulting Staff, Department of Specialist Rehabilitation Services, Hutt Valley District Health Board, New Zealand
Disclosure: Nothing to disclose.

Managing Editor

David A Stringer, BSc, MBBS, FRCR, FRCPC, Professor, National University of Singapore; Head, Diagnostic Imaging, KK Women's and Children's Hospital, Singapore
David A Stringer, BSc, MBBS, FRCR, FRCPC is a member of the following medical societies: British Columbia Medical Association, Canadian Association of Radiologists, European Society of Paediatric Radiology, Ontario Medical Association, Radiological Society of North America, Royal College of Physicians and Surgeons of Canada, Royal College of Radiologists, and Society for Pediatric Radiology
Disclosure: Sirius d'innovation None Board membership

CME Editor

Robert M Krasny, MD, Consulting Staff, Department of Radiology, The Angeles Clinic and Research Institute
Robert M Krasny, MD is a member of the following medical societies: American Roentgen Ray Society and Radiological Society of North America
Disclosure: Nothing to disclose.

Chief Editor

Eugene C Lin, MD, Consulting Radiologist, Virginia Mason Medical Center; Clinical Assistant Professor of Radiology, University of Washington School of Medicine
Eugene C Lin, MD is a member of the following medical societies: American College of Nuclear Medicine, American College of Radiology, Radiological Society of North America, and Society of Nuclear Medicine
Disclosure: Nothing to disclose.

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

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