Hirschsprung's disease in a kindred: a possible clue to the genetics of the disease

J Pediatr Surg. 1982 Oct;17(5):632-4. doi: 10.1016/s0022-3468(82)80124-3.


A nine generation kindred, the first generation dating back to the early 18th century, existing in the Mennonite population of central Pennsylvania is described in terms of the incidence of documented and presumptive Hirschsprung's disease. This kindred was developed by tracing back family lines, by the use of the "circle letter" and three family history books, and by personal interviews with key family members. In the ninth (current) generation, involving at least 5 families, 8 out of 14 children (57%) have documented evidence of Hirschsprung's disease; 4 out of 14 had congenital deafness (29%); 2 had Waardenburg's syndrome (14%); and 1 had Down's syndrome (7%). Only 1 out of the 14 had total colonic involvement. Investigation of the sixth-ninth (last 4) generations shows 22 out of 100 (22%) to have definite or strongly presumptive evidence of Hirschsprung's disease. The opportunity to study this unique kindred, which can be traced back to a single source, exhibiting a very high incidence of Hirschsprung's disease with an unusually high incidence of associated congenital anomalies and without significant association of total colonic disease has provided us with a better understanding of the genetics underlying this disease.

MeSH terms

  • Consanguinity
  • Down Syndrome / complications
  • Female
  • Hirschsprung Disease / complications
  • Hirschsprung Disease / genetics*
  • Humans
  • Male
  • Pedigree