A family study of Hirschsprung's disease

SUMMARY Family data are reported on 207 index cases, in 203 families, attending The Hospital for Sick Children from July 1948 to December 1959 with Hirschsprung's disease. Of these 82% were of the ‘short‐segment’ variety, 17 % of the ‘long‐segment’ variety and 2 (1 %) were of the very long‐segment variety extending to the duodenojejunal junction. The incidence of all varieties in the general population is estimated to be between 1 in 2000 and 1 in 10,000 total births. The overall sex ratio is 3–6 but this decreases with the length of aganglionic segment, being 1–5 for long‐segment cases and 4–7 for short‐segment cases. There is no effect of maternal age and birth order. The only associated malformation is Down's syndrome, which was present in 3 of the 207 index patients. Parental consanguinity was found only once in the series. A male monozygotic twin pair were both index patients. Three surviving dizygotic co‐twins of index patients were unaffected. Thirteen sib pairs were concordant for the length of aganglionic segment. The proportion affected of sibs of short‐segment cases was 9 in 173 brothers, and 1 in 145 sisters, and of long‐segment index cases 5 in 35 brothers and 3 in 28 sisters. Two children of index patients were both unaffected. One uncle, two nephews, and five first cousins were affected. The two nephews were exceptional in that they were long‐segment cases while the index patient was a short‐segment case. It is suggested on the analogy of the experimental work of Yntema & Hammond with the chick embryos, that the development of Hirschsprung's disease is due to a partial interference with the migration of neuroblasts from the lower cranial‐upper cervical neural crest to the gut wall. No simple hypothesis may yet be put forward as to the nature of the genetic factors predisposing to Hirschsprung's disease. We wish to thank the consultant staff of The Hospital for Sick Children for access to their patients, the staffs of the hospitals mentioned in Appendix B, for supplying information about, and sending histological material from, patients* relatives, and Dr J. A. Fraser Roberts for helpful criticism. We are greatly indebted to Miss A. R. Buck for most of the home‐visiting of the families and her help with the analysis.