Hirschsprung disease; congenital megacolon; colonic aganglionosis; aganglionic megacolon

Etiology

• disorders in which congenital intestinal aganglionosis is seen include:
  • trisomy 21
  • Waardenburg syndrome
  • cartilage-hair hypoplasia
  • Smith-Lemli-Opitz syndrome type II
  • MEN2A & MEN2B
  • primary central hypoventilation syndrome (Ondine-Hirschsprung disease)
  • ABCD syndrome

Epidemiology

• generally presents in infants
• uncommonly presents in adults, generally in males

Pathology

• congenital absence of parasympathetic innervation of the lower intestinal tract, resulting in congenital megacolon
• absence of enteric neurons in the colonic submucosa & myenteric plexus
• heterogeneous disorder

Genetics

• associated with defects in:
  • RET
  • endothelin B receptor
  • endothelin-3 (type 4)
  • GDNF (type 3)
  • endothelin converting enzyme-1
  • neural cell adhesion molecule L1 (L1CAM) may modify effects of another Hirschsprung disease-associated gene
• genetic variations in NRTN may contribute to Hirschsprung disease, in association with mutations of RET gene, & possibly mutations in other loci

Clinical manifestations

• occurs as an isolated trait in 70% of patients
• occurs with additional congenital anomalies in 18% of cases

Laboratory

• colonoscopy with full-thickness biopsy of affected mucosa

Radiology

• barium enema may show narrow segment of colon with proximal dilation

Management

• Botox injection into the internal rectal sphincter
• anorectal myomectomy

More general terms

• aganglionosis
• icolonic motility disorder
• genetic disease of the gastrointestinal tract

More specific terms

• Hirschsprung disease with microcephaly & iris coloboma
• Hirschsprung disease, cardiac defects & autonomic dysfunction

Additional terms

• megacolon

Patient information

Hirschsprung disease patient information

Database

• OMIM: https://mirror.omim.org/entry/142623
• OMIM: https://mirror.omim.org/entry/164761
• OMIM: https://mirror.omim.org/entry/613712