One might think that Hirschsprung’s disease (congenital megacolon) should be passé as a medical problem. After all, many genes, including RET, GDNF, NRTN, EDNRB, EDN3, ECE1, PHOX2b, SOX10, PAX3 and SMADIP1 (SIP1, ZBFX1B),^1–,⁷ have successfully been linked to its pathogenesis. Knowledge of the actions and interactions of these genes and their products has enabled the processes by which the bowel is colonised to be, if not completely understood, at least comprehended in general terms.^3,8,9,10 Effective treatment for Hirschsprung’s disease, moreover, exists in the surgical removal of the aganglionic segment of bowel.^11–,¹³ Unfortunately, the medical problems posed by Hirschsprung’s disease continue despite the lengthy list of genes implicated in its generation and the progress that has recently been made in understanding enteric nervous system (ENS) development. Unresolved medical problems continue because advances made in comprehending genes and pathogenesis have not been translated into new and improved methods of treatment; moreover, although surgical techniques are evolving and associated morbidity is decreasing,^12,13 the surgical treatment of Hirschsprung’s disease essentially converts an otherwise lethal defect into a chronic condition with which many, if not most, patients must learn to cope.^14,15

Hirschsprung’s disease occurs when a variable length of terminal bowel is congenitally aganglionic. Because the reflexes and behaviours mediated by the ganglionated plexuses of the ENS are essential for propulsive motility and normal secretion,¹⁶ aganglionosis results in a pseudoobstruction that, if left untreated, is incompatible with life. Reliable modern statistics on untreated Hirschsprung’s disease are not available because failure to treat it is immoral; however, aganglionosis …