Clinical Trial: Hirschsprung Disease Genetic Study

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Observational

Official Title: Genetic Analysis of Hirschsprung Disease

Brief Summary: Hirschsprung disease is a genetic condition caused by lack of nerve cells in varying lengths of the intestines. This study will investigate the complex genetic basis of the disease, which involves multiple interacting genetic factors.

Detailed Summary:

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 congenital central hypoventilation syndrome. Hirschsprung disease is a genetic condition with autosomal dominant, autosomal recessive, and multigenic patterns of inheritance described.

Dr. Aravinda Chakravarti's laboratory at Johns Hopkins University has been investigating the genetics of Hirschsprung disease (HSCR) for more than twenty five years. The goal of this research study 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, the study aims to determine the frequency with which mutations in any human gene lead to familial and isolated forms of HSCR. Further, the study will collect clinical information and investigate possible genotype - phenotype correlations.

Molecular analysis using markers and sequencing, and statistical analysis of these data will be used to identify regions of human chromosomes where putative HSCR disease genes may be located. In addition, the DNA sequence of known and/or suspected HSCR genes will be assessed in individual patients and their family members, in search of causative HSCR susceptibility variants and variants that may affect presentation of the disease and treatment outcomes. Phenotypic information will include pathology, surgical, and other clinical outcomes related to Hirschsprung disease. This study will hopefully lead to a better understanding of the genetics of HSCR and,
Sponsor: Johns Hopkins University

Current Primary Outcome:

  • Discovery and characterization of common genetic variation associated with Hirschsprung disease [ Time Frame: DNA is isolated up to 1 year after enrollment ]
    Genome-wide assays of common genetic variation will be assessed using single nucleotide polymorphism (SNP) arrays
  • Discovery and characterization of copy number variants associated with Hirschsprung disease [ Time Frame: DNA is isolated up to 1 year after enrollment ]
    Copy number variation will be detected using next generation sequencing data and high resolution microarrays that allow for detection of copy number variants across the genome
  • Discovery and characterization of rare genetic variation associated with Hirschsprung disease [ Time Frame: DNA is isolated up to 1 year after enrollment ]
    Exome sequencing will be used to detect rare variation across all genes in the genome


Original Primary Outcome:

Current Secondary Outcome:

  • Correlation of genetic variants with location of transition zone in Hirschsprung disease [ Time Frame: Baseline pathology data is obtained up to 1 year after enrollment ]
    Pathology records and surgical records will be used to determine transition zone
  • Correlation of genetic variants with risk for enterocolitis in Hirschsprung disease [ Time Frame: Baseline clinical data is obtained up to 1 year after enrollment ]
  • Characterization of Hirschsprung disease that co-occurs with a known chromosomal disorder [ Time Frame: Baseline clinical data is obtained up to 1 year after enrollment ]
  • Characterization of Hirschsprung disease that co-occurs with a known single gene syndrome [ Time Frame: Baseline clinical data is obtained up to 1 year after enrollment ]
  • Characterization of Hirschsprung disease that co-occurs with other congenital anomalies without a known diagnosis [ Time Frame: Baseline clinical data is obtained up to 1 year after enrollment ]
  • Correlation of genetic variants with need for repeat pull-through surgery in Hirschsprung disease [ Time Frame: Baseline clinical data is obtained up to 1 year after enrollment and follow up data is obtained up to 100 years after enrollment ]
    Assessment of complications that lead to eventual repeat pull-through surgery
  • Correlation of genetic variants with difficulty controlling stools after pull-through surgery [ Time Frame: Baseline clinical data is obtained up to 1 year after enrollment and follow up data is obtained up to 100 years after enrollment ]
  • Correlation of genetic variants with chronic constipation after pull-through surgery [ Time Frame: Baseline clinical data is obtained up to 1 year after enrollment and follow up data is obtained up to 100 years after enrollment ]


Original Secondary Outcome:

Information By: Johns Hopkins University

Dates:
Date Received: May 24, 2007
Date Started: January 2001
Date Completion: March 2025
Last Updated: February 23, 2017
Last Verified: February 2017