Description

• A disease of the colon characterized by functional obstruction, fecal accumulation, and colonic dilation:
  • 74–80% of cases involve rectosigmoid colon, 12–22% involve long segment of the colon (splenic flexure or transverse colon), and 4–13% of cases with total colonic involvement (to terminal ileum).
• System(s) affected: gastrointestinal, nervous
• Synonym(s): aganglionic megacolon; Hirschsprung disease; Zuelzer-Wilson disease (total colonic aganglionosis)

Pediatric Considerations
Some infants have only mild or intermittent constipation with intervening bouts of diarrhea. These patients typically have aganglionosis of a short segment of distal rectum. These cases may not be diagnosed until later in infancy or childhood.

Epidemiology

• Predominant age: infancy
• Predominant sex: males > females for short segment (4:1); males > females for long segment (5:4)

Incidence

• 1/2,000 to 5,000 births in the United States (white 91%, black 8%, Asian 0.5%)
• 2.8/10,000 live births in Asians (1)

Etiology and Pathophysiology

• Congenital absence of Auerbach and Meissner autonomic plexuses in bowel wall (usually limited to the colon)
• Aganglionosis results in the lack of propagation of propulsive waves of muscle contraction and absence of relaxation of the internal anal sphincter.
• Obstruction may begin at anus and extend proximally to varying portions of the colon and small bowel.

Genetics

• Familial inheritance: 50-fold increase in prevalence
• Associated with Down syndrome
• Dominant mutations in the RET gene are found in 50% of familial patients with Hirschsprung disease and in 15–35% of patients with sporadic Hirschsprung disease (10q11.2 locus) (1).

Risk Factors

• Family history of Hirschsprung disease
• Offspring risk if parent has short segment is 2%; if parent has long segment, risk is up to 50%.
• Sibling risk if male affected: Female has 0.6% risk (short segment).
• Sibling risk if female affected: Male has 18% risk (long segment).

Commonly Associated Conditions

• Associated neurologic, cardiovascular, urologic, and gastrointestinal anomalies in 11–30% of patients (1)
• Secondary aganglionic megacolon may be a late complication of Chagas disease.
• Down syndrome (4-fold increase in incidence)
• Cardiovascular defects (6%)
• Urogenital anomalies (11%)
• Dandy-Walker; Waardenburg; Ondine; Sipple syndromes
• Cleft palate
• Congenital small or large bowel atresia
• Multiple endocrine neoplasia (MEN)-2B syndrome
• Prematurity