Introduction and historical aspects

Hirschsprung's disease (HD) is characterized by an absence of ganglion cells in the nerve plexuses of the distal large bowel. The lack of ganglion cells produces a functional obstruction and leads to dilatation of the bowel that is proximal to the aganglionic zone. The commonly quoted incidence of HD is 1:5000. The classic description of HD was first presented in detail by a Danish pediatrician, Harald Hirschsprung in 1886. The absence of ganglion cells in the distal large bowel was first reported by Tittel, but the crucial role of this finding as the primary pathology was not appreciated until the late 1940s. In 1948 the first successful operation for HD was performed by Swenson and Bill. This was a rectosigmoidectomy and later became known as the Swenson operation.

The functional obstruction caused by a lack of enteric ganglion cells in the distal bowel results in severe constipation and failure to thrive and may be fatal because of enterocolitis. The exact embryologic mechanism of the development of HD is controversial but the most favored theory is defective neuronal migration. Several genes (RET, GDNF, EDN3, ETRB) have been shown to cause HD both in humans and animal models. However, single gene defects explain only a minority of HD cases; in the majority, the cause of HD is probably multifactorial and multigenic.

In its classic form HD is restricted to the rectosigmoid region. Classic HD comprises 75–80% of all patients.