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A. Definition navigator

  1. Functional obstruction of rectum or colon
  2. Results from variable length of colonic aganglionosis

B. Epidemiologynavigator

  1. Occurs in 1 in 5000 births
  2. Approximately 3:1 male to female
  3. 15 % diagnosed by 1 month and 60 % by 3 months
  4. No racial predilection
  5. Increased incidence with Down's Syndrome and chromosome 13q deletion

C. Pathophysiologynavigator

  1. Failure of the migration of neuroblasts along the GI tract
    1. Absent myenteric plexi in distal colon and rectum
    2. Aganglionic gut loses tonic neural inhibition and remains contracted
    3. Absence of neurons containing vasoactive intestinal polypeptide and nitric oxide
  2. Development anomaly occurs between the 7th and 12th week of gestation
    1. Results in an absence of ganglion cells in the myenteric plexus of colon
    2. Abnormally innervated distal colon
    3. Remains tonically contracted
    4. Obstructs the flow of feces
  3. Bowel proximal to the agangionic zone becomes dilated with stool
    1. 80% of cases occur in distal sigmoid and rectum
    2. 15% may affect colon distal to hepatic flexure
  4. Etiology [3]
    1. Congenital disease with autosomal recessive (AR) and autosomal dominant (AD) forms
    2. Interactions between several pathways including RET, EDNRB, SOX10, SIP1
  5. RET [4]
    1. Receptor tyrosine kinase involved in development and oncogenesis
    2. Some patients with AD Hirschprung Disease have loss-of-function mutations in RET gene
    3. Specific mutations in RET may modulate short- versus long-form of Hirschprung
    4. RET alleles on both chromosomes contribute to phenotype in Hirschprung
    5. RET mutations also cause MEN2 syndrome (these are usually gain-of-function)
    6. Screen for MEN2 in patients with HD
  6. EDNRB
    1. EDNRB is Endothelin B receptor
    2. Many patients with AR form have mutations in gene for

D. Symptomsnavigator

  1. Failure to pass meconium within 48 hours
  2. Neonates at higher risk for necrotizing enterocolitis
    1. Increased intraluminal pressure compromises intestinal blood flow
    2. This leads to ischemic bowel with necrosis and perforation
  3. Abdominal obstruction with poor feeding, bilious vomiting and abdominal distention
  4. Constipation prior to introduction of solid foods
  5. Patients with milder forms present later with chronic constipation
  6. Chronic stasis and bacterial overgrowth in the distended, functionally obstructed colon
    1. About 15% develop severe complications due to bacterial overgrowth
    2. C. difficile colitis
    3. Frank sepsis

E. Physical Examinationnavigator

  1. Rectal exam may reveal narrow high pressure area
  2. Absence of feces in the ampulla or rectal vault

F. Diagnosis navigator

  1. Abdominal Radiograph ("KUB")
    1. Changes typical of low obstruction
    2. Abundant stool in distended colon
    3. Paucity of rectal air
  2. Barium Enema: dilation of normal proximal colon and constriction of aganglionic regions
  3. Anal Manometry
    1. Measures response of spincters to inflation of a balloon
    2. Shows lack of reflex relaxation in the internal anal spincter upon rectal distention
  4. Rectal biopsy 2-4 cm from anal verge
    1. Absence of rectal Meissner and Auerbach's plexuses (ganglionic cells)
    2. Hypertrophied nerve bundles between circular and longitudinal muscles in submucosa
    3. Gold standard for diagnosis

G. Treatmentnavigator

  1. Prevention of enterocolitis and relief of intestinal obstruction
  2. Staged surgical repair
  3. Initially diverting colostomy
  4. Removal of aganglionic segment colon
  5. Secondary re-anastomosis with ileal pull through
  6. Complications include anastomotic leaks and strictures

References navigator

  1. Rudolph C and Benaroch L. 1995. Pediat in Rev. 16(1):5 abstract
  2. Goyal RK and Hirano I. 1996. NEJM. 334(17):1106 abstract
  3. McCabe ERB. 2002. Lancet. 359(9313):1170
  4. Fitze G, Cramer J, Ziegler A, et al. 2002. Lancet. 359(9313):1200 abstract