Hirschsprung's disease

Hirschsprungs disease (HD, HSCR) is a congenital aganglionosis of the distal gut with variable extend. The pathogenic development of HD is caused by disturbance of cell migration from the neural crest towards the distal gut. Therefore HD is a neurocristopathy. Genetic factors have been identified in about half of the familial cases and 15-35% of sporadic cases. Mutations in the RET-protooncogen appear to be present in most sporadic cases, together with other genetic defects. Multiple endokrine neoplasia type 2a (MEN 2a) is present in a small number of cases (< 5%), associated with a high risk for medullary thyroid carcinoma and pheochromocytoma. Associated syndromes include also Down-syndrome, Waardenburg-syndrome and Smith-Lemli-Opitz-syndrome. Diagnosis is based on histological demonstration of complete absence of enteric ganglion cells in deep biopsies that include sufficient submucosa, along with the demonstration of hypertrophic acetylcholinesterase-positive nerve trunks that appear to arise from extrinsic innervation. Important is the genetic detection of patients with predisposition for medullary thyroid carcinoma and pheochromocytoma. Therapeutic goal is a one-stage resection of the aganglionic segment and pull-through of the euganglionic gut with an anastomosis in the anal region. HD is still a fascinating disease and serves as a model for embryologic, genetic, oncologic, endocrine and epidemic research.