Autonomic Dysfunction in Children with Hirschsprung's Disease

During embryogenesis, two differenttransmembrane receptors, Ret and Ednrb, together withtheir ligands, respective, GDNF and endothelin-3, areinvolved in the migration and differentiation of entericganglion cells, sympathetic neurons and melanocytes fromthe neural crest. Mutations in these genes have beenfound in a number of human and murineneurocristopathies, including Hirschsprung's disease.RET and GDNF knockouts suggest that they are involved in acorrect autonomic nervous system formation. The aim ofthis study is the evaluation of the autonomic nervoussystem in patients with Hirschsprung's disease. Seventeen children (mean age: 8.6 years) withHirschsprung's disease and 19 age- and sex-matchedcontrol children (mean age: 9.9 years) underwentpupillary and cardiovascular testing of sympatheticadrenergic and cholinergic function and cardiovagalcholinergic function. Seven of 17 patients withHirschsprung's disease were affected by autonomicdysfunction. Three of seven patients had evidence ofsympathetic denervation, two showed a parasympatheticdysfunction, whereas the remaining two had dysfunctionof both sympathetic and parasympathetic tests. Our datain a small number of patients with Hirschsprung's disease show that a subset of these patientsexhibits measurable autonomic dysfunction. A RETmutation has been found in one of them. As for theabsence of the enteric ganglion cells, autonomicdysfunction in these subjects seems to bepolygenic.