Increased Incidence of Hirschsprung's Disease in Patients with Hypoplastic Left Heart Syndrome--a Common Neural Crest-derived Etiology?

Background: The enteric ganglions and the outflow tract of the heart originate from the neural crest. Impaired migration or differentiation of the neural crest cells causes Hirschsprung's disease (HD) and results in the development of cardiac outflow tract malformations. We hypothesize that the incidence of HD and bowel disorders associated with HD are increased in patients with hypoplastic left heart syndrome (HLHS) including left cardiac outflow tract obstruction.

Methods: All consecutive patients treated for HLHS at our institution during 1969 to 2005 were retrospectively reviewed. The number of patients with histologically confirmed HD or clinical findings characteristic of HD such as constipation and delayed meconium were recorded from the patient records.

Results: A total of 113 patients (65 males) were identified. At the time of survey, 57 patients (51%) were alive. Overall, there were 26 (23%) patients with constipation, and 9/23 (39%) had delayed passage of meconium after 48 hours. Despite frequent bowel disorders only 4 (3.5%) patients had undergone histologic examination of the rectum. Hirschsprung's disease was detected in 3 patients (95% confidence interval, 0.62-8.77). The expected number of HD cases in the study population was 0.026 giving 117-fold significant increase in the incidence of HD among patients with HLHS when compared to general Finnish population.

Conclusions: The incidence of HD is increased in patients with HLHS. These results point to a common neural crest-derived embryologic origin of HD and HLHS and warrant further studies.