Hirschsprung disease

Definition And Epidemiology

Definition: A congenital developmental disorder of the enteric nervous system (neurocristopathy) resulting in an aganglionic megacolon.
Pathology: Characterized by the complete absence of parasympathetic intrinsic ganglion cells in the submucosal (Meissner) and myenteric (Auerbach) plexuses.
Incidence And Demographics: Occurs in 1 in 5000 live births. There is a 4:1 male predominance in short-segment disease, whereas long-segment disease exhibits an equal gender distribution.
Associated Syndromes: Frequently associated with Trisomy 21 (most common), Multiple Endocrine Neoplasia (MEN) type 2A, Congenital Central Hypoventilation Syndrome (Ondine's curse), Waardenburg syndrome, and Mowat-Wilson syndrome.

Embryologic Arrest: Pathogenesis involves the premature arrest of craniocaudal migration of vagal neural crest cells in the hindgut between the 5th and 12th weeks of gestation.
Motility Defect: The aganglionic segment remains permanently contracted due to the absence of non-adrenergic, non-cholinergic inhibitory innervation. This causes a functional intestinal obstruction, leading to progressive secondary dilation of the proximal, normally-innervated bowel.
Genetics: It is a multigenic and multifactorial disorder associated with mutations in the RET (most common), GDNF, EDNRB, EDN3, and SOX10 genes.

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

Classic Triad: Failure to pass meconium within the first 24–48 hours of life, bilious emesis, and progressive abdominal distension.
Hirschsprung-Associated Enterocolitis (HAEC): A life-threatening presentation characterized by lethargy, fever, severe abdominal distension, and explosive foul-smelling or bloody diarrhea. It can rapidly progress to toxic megacolon and sepsis.

Symptomatology: Presents with chronic, severe, refractory constipation, passage of ribbon-like or pellet stools, and failure to thrive.
Physical Examination: Reveals a markedly distended, tympanitic abdomen and a tight anal sphincter with an empty rectal vault.
Squirt Sign: Explosive discharge of foul-smelling liquid stool and gas occurs upon withdrawal of the examining finger during a digital rectal examination.

Diagnostic Modality	Key Findings And Utility
Unprepared Contrast Enema	Identifies a radiographic "transition zone" (funnel-shaped narrowing between the dilated proximal colon and the smaller aganglionic distal segment). Demonstrates a rectosigmoid ratio <1 and delayed contrast retention on 24-hour films.
Anorectal Manometry	Demonstrates the absence of the Rectoanal Inhibitory Reflex (RAIR), meaning the internal anal sphincter fails to relax upon rectal balloon distension.
Rectal Suction Biopsy	Gold Standard. Must be obtained 2-3 cm above the dentate line. Confirms the total absence of ganglion cells.
Histochemical Staining	Reveals increased thick, knotted acetylcholinesterase (AChE)-positive hypertrophied nerve fibers and a loss of calretinin immunoreactivity in the aganglionic segment.

Clinical Feature	Hirschsprung Disease	Functional Constipation
Onset Of Symptoms	Neonatal period or infancy.	Toddler or preschool age (acquired).
Meconium Passage	Delayed (>48 hours).	Normal (<48 hours).
Encopresis / Soiling	Rare or completely absent.	Extremely common (overflow incontinence).
Withholding Behavior	Rare or absent.	Common (retentive posturing).
Digital Rectal Exam	Empty ampulla, tight sphincter, squirt sign present.	Enlarged ampulla filled with hard stool.

Immediate bowel decompression utilizing rectal irrigations and nasogastric tube decompression.
Provide rigorous intravenous fluid resuscitation and initiate broad-spectrum antibiotics if enterocolitis (HAEC) is suspected.

Primary Pull-Through: The definitive treatment involves resection of the aganglionic segment followed by a pull-through of normally innervated proximal bowel and end-to-end anastomosis to the anal margin (e.g., Soave procedure).
Staged Procedure: An initial decompressive diverting colostomy followed by a delayed pull-through is strictly reserved for unstable neonates, active severe enterocolitis, massive proximal dilation, or extreme prematurity.

Early Complications: Anastomotic leaks and stricture formation.
Late Complications: Recurrent constipation occurs in up to 8% of patients, and recurrent episodes of Hirschsprung-associated enterocolitis (HAEC) occur in 10-20% of cases postoperatively. Fecal incontinence is also a potential long-term sequela, though symptoms generally improve with age.