Hirschsprung disease

DEFINITION & EPIDEMIOLOGY

Definition: Congenital aganglionic megacolon; developmental disorder of enteric nervous system (neurocristopathy).
Pathology: Characterized by complete absence of parasympathetic intrinsic ganglion cells in submucosal (Meissner) and myenteric (Auerbach) plexuses.
Incidence: 1 in 5000 live births.
Demographics: Male predominance (4:1) in short-segment disease; equal gender distribution in long-segment disease. Rare in premature infants.
Associated Syndromes: Trisomy 21 (most common), Multiple Endocrine Neoplasia (MEN) type 2A, Congenital Central Hypoventilation Syndrome (Ondine’s curse), Waardenburg syndrome, Mowat-Wilson syndrome, and cardiovascular/urogenital anomalies.

Embryology: Premature arrest of craniocaudal migration of vagal neural crest cells in hindgut between 5th and 12th weeks of gestation.
Motility Defect: Aganglionic segment permanently contracted due to lack of non-adrenergic-non-cholinergic inhibitory innervation. Interstitial cells of Cajal network disrupted. Causes functional obstruction and progressive proximal bowel dilation.
Genetics: Multigenic/multifactorial with low, sex-dependent penetrance. Associated with mutations in RET (most common), GDNF, EDNRB, EDN3, and SOX10 genes.

Type	Extent of Aganglionosis	Frequency
Short Segment (Classic)	Limited to rectum and sigmoid colon.	70–80%.
Long Segment	Extends proximal to sigmoid colon (typically up to splenic flexure).	10–20%.
Total Colonic Aganglionosis	Involves entire colon and <50 cm of distal ileum.	3–6%.
Total Intestinal Aganglionosis	Involves longer segments of small bowel; rare.	<1%.

Failure to pass meconium within first 24–48 hours of life (seen in 60-90% of patients).
Abdominal distension, bilious emesis, feeding intolerance.
Hirschsprung-Associated Enterocolitis (HAEC): Life-threatening presentation with lethargy, fever, severe abdominal distension, and explosive foul-smelling or bloody diarrhea. Leads to toxic megacolon, sepsis, and high mortality.

Chronic, severe, refractory constipation; ribbon-like stools.
Failure to thrive; hypoproteinemia (protein-losing enteropathy).
Physical Examination: Distended abdomen; tight anal sphincter. Empty rectal vault.
“Squirt Sign”: Explosive discharge of foul-smelling liquid stool and gas upon withdrawal of examining finger.

Modality	Key Findings & Utility
Unprepared Contrast Enema	Identifies “transition zone”: funnel-shaped narrowing between normal dilated proximal colon and smaller-caliber obstructed distal aganglionic segment. Rectosigmoid ratio <1. Contrast retention on 24-hour delayed films.
Anorectal Manometry	Absence of Rectoanal Inhibitory Reflex (RAIR) (failure of internal anal sphincter to relax upon rectal balloon distension). Highly sensitive in children >3 months; normal study excludes disease.
Rectal Suction Biopsy	Gold Standard. Must be taken 2-3 cm above dentate line to avoid physiological hypoganglionic zone.
Histopathology	Total absence of ganglion cells in submucosal/myenteric plexuses. Increased thick, knotted acetylcholinesterase (AChE)-positive hypertrophied nerve fibers in muscularis mucosae and lamina propria. Loss of calretinin immunoreactivity.

Feature	Functional Constipation	Hirschsprung Disease
Onset	Beyond 1 year of age; acquired	Within infancy/at birth; congenital.
Meconium Passage	Normal	Delayed (>24-48 hours).
Encopresis/Soiling	Common	Rare/Absent.
Stool Withholding Behavior	Common	Rare.
Failure to Thrive	No	Possible/Common.
Rectal Examination	Ampulla enlarged and filled with stool	Ampulla empty; “squirt sign” on finger withdrawal.
Anorectal Manometry	RAIR present	RAIR absent.

Definitive Treatment: Resection of aganglionic segment, pull-through of normally innervated proximal bowel, and anastomosis to anal margin (preserving sphincter mechanism).
Techniques: Single-stage transanal endorectal pull-through (Soave procedure) often performed laparoscopically.
Staged Approach: Initial decompressive colostomy with delayed pull-through; reserved for unstable neonates, severe enterocolitis, or massive proximal dilation. Total colonic aganglionosis requires ileal-anal anastomosis.

Early postoperative complications: Anastomotic leak, stricture.
Long-term sequelae: Recurrent constipation (8%), fecal incontinence, and recurrent episodes of Hirschsprung-associated enterocolitis (HAEC) (10-20% postoperatively). Symptoms generally improve with age.