Hirschsprung’s Disease: Two Cases of Total Intestinal Aganglionosis

Introduction/Objective Hirschsprung’s disease is a disorder associated with an absence of ganglion cells in a segment of the bowel. Total colonic and small bowel aganglionosis occurs in less than 1% of all Hirschsprung’s disease patients. Even rarer is the finding of Haddad syndrome, the coexistence of congenital central hypoventilation syndrome and Hirschsprung’s disease. Congenital central hypoventilation syndrome has approximately 1,000 reported cases, with colonic aganglionosis being associated with 15-20% of those cases. The prevalence of Hirschsprung’s disease with congenital renal anomalies may be another underreported finding. Methods Here, we report two rare cases of Hirschsprung’s disease with significant extension in the small bowel. One case involves a 38-week gestational age male infant admitted for apnea and another case involves 39-week gestational age female infant admitted for vomiting. Results Both infants had rectal suction biopsies confirming the absence of ganglion cells. The male infant had mapping biopsies which histologically showed hypertrophic nerve fibers and an absence of ganglion cells in the colon extending up to 70 cm proximal to the ileocecal valve. Calretinin immunostaining confirmed aganglionsis. Genetic testing showed a PHOX2B gene mutation carrying 32 polyalanine repeat mutations, confirming a diagnosis of congenital central hypoventilation syndrome coexisting with Hirschsprung’s disease. The female infant had intraoperative frozen sections that identified ganglion cells throughout the colon. On permanent sections, there was an absence of ganglion cells in the upper rectum extending up to 65 cm proximal to the ileocecal valve. She also was noted to have agenesis of the left kidney and a urachal remnant. Genetic testing was negative for RET mutations. Conclusion Overall, these cases provide further information on a rare variant of Hirschsprung’s disease that includes significant portions of the small bowel. Additionally, this study adds to the documented reports of Haddad syndrome and the connections between renal anomalies with Hirschsprung’s disease. Last, this series alludes to the difficulties of frozen section diagnosis of this disease.