Clinical Research Studies

Hirschsprung disease (HSCR) is a neurodevelopmental defect resulting from the absence of nerve (ganglion) cells in the gastrointestinal tract. The disorder has a population incidence of 1/5,000 live births and most often occurs as an isolated phenotype. However, approximately 30% of HSCR cases are associated with other birth defects such as Down syndrome, deafness, hypopigmentation, and Congenital Central Hypoventilation syndrome (CCHS, aka Ondine’s curse). Hirschsprung disease is a genetic condition sometimes recognized with autosomal dominant and autosomal recessive inheritance, but is generally multifactorial. While several genes associated with HSCR have been identified, it is expected that additional genes play important roles 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 the diverse 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. HDRC members (surgeon champions at diverse medical centers) will collect samples and data through a multi-site study where Dr. Aravinda Chakravarti’s laboratory at NYU School of Medicine serves as the coordinating center. The data and samples collected by HDRC members will not only be available for genetic studies, but will form a biobank from which HDRC members can request access to de-identified samples and data for use in their own IRB-approved studies. The goal of the genetic studies carried out with HDRC samples is to complete the identification of HSCR susceptibility genes and to better understand the complex inheritance of HSCR in families by whole genome mapping and sequencing studies. We also intend to ascertain the frequency with which HSCR gene variants, individually and together, lead to the diverse forms of HSCR. Finally, we use these results together with the clinical information we collect to investigate possible genotype-phenotype correlations and their relationship with medical, surgical and pathological data on participants.