Hirschsprung Disease Genetic Study

November 28, 2023 updated by: NYU Langone Health

Genetic Analysis of Hirschsprung Disease

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.

Study Overview

Detailed Description

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 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, further down the road, improved diagnosis, treatment, and genetic counseling.

This study asks volunteers to:

  1. Complete a medical/family history questionnaire
  2. Provide access to some medical records
  3. Submit blood samples from the individual(s) affected with Hirschsprung disease and his/her parents (if available)

Study Type

Observational

Enrollment (Estimated)

3000

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • New York
      • New York, New York, United States, 10016
        • Recruiting
        • New York University School of Medicine
        • Contact:
        • Principal Investigator:
          • Aravinda Chakravarti, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

1 week to 100 years (Child, Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Sampling Method

Non-Probability Sample

Study Population

The study population includes individuals with Hirschsprung disease and their family members.

Description

Inclusion Criteria:

- Individuals with Hirschsprung disease and their first degree relatives (any segment length of disease, with or without other congenital anomalies or health problems, single or multiple affected individuals in family)

Exclusion Criteria:

  • Unable or unwilling to provide sample for genetic studies
  • Individual, parent, or guardian unable to comprehend and provide informed consent

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Observational Models: Family-Based
  • Time Perspectives: Prospective

Cohorts and Interventions

Group / Cohort
Intervention / Treatment
Families with Hirschsprung Disease
Individuals with Hirschsprung disease and their affected and unaffected relatives.
Blood, saliva, or DNA samples are requested from all study participants. The blood or saliva samples are used to isolate DNA in all participants. Blood samples are also used to establish cell lines in some participants.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
DNA is isolated up to 1 year after enrollment
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
DNA is isolated up to 1 year after enrollment
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
DNA is isolated up to 1 year after enrollment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
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
Baseline pathology data is obtained up to 1 year after enrollment
Correlation of genetic variants with risk for enterocolitis in Hirschsprung disease
Time Frame: Baseline clinical data is obtained up to 1 year after enrollment
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
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
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
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
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 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
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
Baseline clinical data is obtained up to 1 year after enrollment and follow up data is obtained up to 100 years after enrollment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Collaborators

Investigators

  • Principal Investigator: Aravinda Chakravarti, PhD, NYU Langone Health

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 1, 2001

Primary Completion (Estimated)

December 1, 2028

Study Completion (Estimated)

December 1, 2028

Study Registration Dates

First Submitted

May 24, 2007

First Submitted That Met QC Criteria

May 24, 2007

First Posted (Estimated)

May 25, 2007

Study Record Updates

Last Update Posted (Actual)

November 29, 2023

Last Update Submitted That Met QC Criteria

November 28, 2023

Last Verified

November 1, 2023

More Information

Terms related to this study

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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