Hirschsprung disease (HSCR) is a birth defect resulting from the absence of nerve (ganglion) cells in the gastrointestinal tract. Hirschsprung disease has a population incidence of 1/5000 live births and most often occurs as an isolated condition. However, approximately 30% of HSCR cases are associated with other birth defects such as Down syndrome, deafness, hypopigmentation, and Ondine's curse (Congenital Central Hypoventilation syndrome (CCHS)). Hirschsprung disease is a genetic condition with autosomal dominant, autosomal recessive, and multigenic patterns of inheritance described. While several genes associated with HSCR have been identified, it is expected that additional genes play a role in the disorder. Furthermore, much remains to be understood about the mechanisms of genetic variants involved in the disease and how variants in multiple genes interact to lead to multiigenic forms of HSCR.
The objective of the Hirschsprung Disease Research Collaborative (HDRC) is to build a large collection of data and biological samples of individuals with HSCR by which genetic data can be linked to detailed and accurate phenotypic information about study participants. The goal of the genetic studies carried out with HDRC samples is to identify genes harboring causative HSCR mutations and to better understand the complex inheritance of HSCR in families by whole genome mapping and sequencing studies. Specifically, we intend to ascertain the frequency with which mutations in any human gene lead to familial and isolated forms of HSCR. Further, clinical information will be used to investigate possible genotype – phenotype correlations and their relationship with medical, surgical and pathological data on patients.