Hirschsprung disease

Pathophysiology: During normal development, neural crest cells migrate craniocaudally to form the enteric nervous system. In Hirschsprung disease, this migration arrests prematurely, resulting in an aganglionic segment that always includes the rectum and extends proximally for a variable distance (most commonly rectosigmoid). The affected segment lacks both the submucosal (Meissner's) and myenteric (Auerbach's) plexuses, causing failure of relaxation and peristalsis in that segment. This creates a functional obstruction, with the normally innervated proximal colon becoming massively dilated (megacolon) as it tries to push stool through the narrowed, non-relaxing distal segment.

Clinical presentation: Classically presents in a newborn with failure to pass meconium within 48 hours of birth, bilious vomiting, and abdominal distension. Digital rectal exam may produce explosive expulsion of stool and gas ('squirt sign'). Older children may present with chronic constipation, failure to thrive, and a history of delayed meconium passage.

Associations: Strongly associated with Down syndrome (Trisomy 21) - occurs in up to 10% of Down syndrome patients. Also associated with RET proto-oncogene mutations (same gene implicated in MEN 2A/2B), and other genetic syndromes.

Diagnosis: Rectal suction biopsy is the gold standard, showing absence of ganglion cells and hypertrophied nerve fibers. Contrast enema may show a 'transition zone' between the narrow aganglionic segment and dilated proximal normal colon.

Treatment: Surgical resection of the aganglionic segment with pull-through procedure to connect normal bowel to the anus.

Complications: Hirschsprung-associated enterocolitis (HAEC) is a serious, potentially life-threatening complication that can occur before or after surgery, presenting with fever, abdominal distension, and diarrhea.