Familial Hirschsprung's disease: study of a Texas cohort.

OBJECTIVE

To better define the types of transmission of Hirschsprung's disease (HD) in order to allow for earlier diagnosis and treatment and reduction of attendant morbidity.

METHODS

A proband with HD was identified. A detailed family history was obtained and a 54-member, five-generation family pedigree constructed and analyzed.

RESULTS

Six members of the kindred presented with classic biopsy-proven HD. Two of the six members were a pair of dizygotic twins. Three additional members had symptoms reminiscent of HD or HD variant (neuronal intestinal dysplasia) and were managed nonoperatively. There was one death related to HD. Hirschsprung's disease was manifested in offspring of both affected parent(s) and unaffected parents. Symptom manifestation was noted to skip generations.

CONCLUSIONS

Analysis of this kindred lends strong evidence to the possibility of autosomal dominant inheritance. This inheritance has a variable penetrance (expression) that may be a factor of mutation or of a spectrum of the disease, ie a type of neural crestopathy. Kindreds of this sort need to be identified to allow for a complete data collection and understanding of the vagaries of HD transmission. This detailed documentation will allow for earlier diagnosis and effective treatment and possible gene localization of the specific defect.