Genetic Analysis of Hirschsprung Disease

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 1/5,000 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 Congenital Central Hypoventilation syndrome (CCHS). Hirschsprung disease is a genetic condition with autosomal dominant, autosomal recessive, and multigenic patterns of inheritance described. The goal of the research study is to identify genes harboring causative HSCR mutations and to better understand the complex inheritance of HSCR in families using whole genome mapping and sequencing studies with functional follow-up of candidate genes and variants. We intend to ascertain the frequency with which mutations in any human gene lead to familial and isolated forms of HSCR. Clinical information is collected to allow investigation of possible genotype - phenotype correlations. The subject population consists of individuals diagnosed with HSCR and their unaffected relatives. Individuals/families are ascertained through support groups, web-based listings of research studies and genetic testing services, an educational study website, and referrals from genetic counselors and physicians. Blood, or tissue, samples are requested from affected individuals and their unaffected relatives.]]>
Inclusion Criteria: Individuals with Hirschsprung disease and their first degree relatives (any segment length of disease, with or without other congenital anomalies, simplex or multiplex family). Exclusion Criteria: Affected individuals unable or unwilling to provide blood or saliva sample for genetic studies. Affected individuals unable to comprehend and provide informed consent. ]]>
The Hirschsprung disease genetic study began recruiting families starting in 1989 at the University of Pittsburgh, was moved to Case Western Reserve University from 1994 - August 2000 to, and then to Johns Hopkins University since September 2000. Samples and clinical data have been collected throughout the study, though the specific clinical data collected has varied over the years as our understanding of Hirschsprung disease has changed, as have the specific consent documents. This dbGaP study includes samples collected and consented at all three locations (University of Pittsburgh, Case Western Reserve University and Johns Hopkins University). The second version of the study includes data of 145 additional subjects.]]>