Hirschsprung’s disease

Abstract

Hirschsprung’s disease (HD) is a relatively common cause of intestinal obstruction in the newborn. It is characterized by absence of ganglionic cells in the distal bowel beginning at the internal sphincter and extending proximally for varying distances. The aganglionosis is confined to rectosigmoid in 75% of patients, the sigmoid, splenic flexure or transverse colon in 17% and total colon along with a short segment of terminal ileum in 8% of patients.1,2 Total intestinal aganglionosis with absence of ganglionic cells from the duodenum to the rectum is the most rare form of HD.3-7 The incidence of HD is estimated to be one in 5000 live births8-10 (Table 55.1). Spouge and Baird studied the incidence of HD in 689 118 consecutive live births in British Columbia and reported an incidence rate for this disease to be one in 4417 live births.9 The disease is more common in boys, with a male-to-female ratio of 4:1.10-12 The male preponderance is less evident in long-segment HD, where the male-to-female ratio is 1.5-2:1.8-10 The enteric nervous system (ENS) is the largest and the most complex division of the peripheral nervous system.13 The ENS contains more neurons than the spinal cord and is responsible for the coordination of normal bowel motility and secretory activities. It is generally accepted that the enteric ganglion cells are derived primarily from the vagal neural crest cells.14-18 During normal development neuroblasts migrate from the vagal neural crest along the bowel wall in a craniocaudal direction from esophagus to anus. The embryonic neural crest arises in the neural tube, originating with the central nervous system, but neural crest cells detach from this tissue via reduction of cell-cell and cell-matrix adhesion. The epithelio-mesenchymal transformation allows crest cells to migrate along pathways. Pathway selection is most likely achieved by balanced combinations of molecules that promote and reduce adhesion.