Familial aspects of Hirschsprung's disease

Twenty-eight of 370 patients (14 families) treated for Hirschsprung's disease (HD) over a 34 year period had a family member with histologically proven HD. These 14 represented 4% of the 351 families: more than one affected child per family in 10 (2.8%) and both parent and child in 2 families. Neuronal intestinal dysplasia (NID) in a parent was associated with total colonic aganglionosis in two siblings of one family which suggests a similar genetic inheritance pattern to HD. Aganglionosis extended beyond the rectosigmoid in 61% of the familial group as opposed to 27% of the non-familial group. A significantly higher number of total colonic aganglionosis (TCA) was noted in those with a family history; 11 out of 28 (39%) as opposed to 19 out of 342 (5.6%) without a family history (p less than 0.001). Fifty percent of males with TCA had a family history but in only 2 cases was this transmitted through a female sibling. Although no significant difference was noted between male and female probands, a three times higher incidence of familial occurrence was noted in females with rectosigmoid disease than in males. Progression of length of segment in succeeding generations was noted in two families. Associated anomalies occurred in 16% without familial occurrence and 11% of the familial group.