Autonomic dysfunction in children with Hirschsprung's disease

During embryogenesis, two different transmembrane receptors, Ret and Ednrb, together with their ligands, respective, GDNF and endothelin-3, are involv ed in the migration and differentiation of enteric ganglion cells, sympathe tic neurons and melanocytes from the neural crest. Mutations in these genes have been found in a number of human and murine neurocristopathies, includ ing Hirschsprung's disease. RET and GDNF knockouts suggest that they are in volved in a correct autonomic nervous system formation. The aim of this stu dy is the evaluation of the autonomic nervous system in patients with Hirsc hsprung's disease. Seventeen children (mean age: 8.6 years) with Hirschspru ng's disease and 19 age- and sex-matched control children (mean age: 9.9 ye ars) underwent pupillary and cardiovascular testing of sympathetic adrenerg ic and cholinergic function and cardiovagal cholinergic function. Seven of 17 patients with Hirschsprung's disease were affected by autonomic dysfunct ion. Three of seven patients had evidence of sympathetic denervation, two s howed a parasympathetic dysfunction, whereas the remaining two had dysfunct ion of both sympathetic and parasympathetic tests. Our data in a small numb er of patients with Kirschsprung's disease show that a subset of these pati ents exhibits measurable autonomic dysfunction. A RET mutation has been fou nd in one of them. As for the absence of the enteric ganglion cells, autono mic dysfunction in these subjects seems to be polygenic.