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RecruitingNCT00478712Updated Jun 4, 2026

Hirschsprung Disease Genetic Study

An observational study in Hirschsprung Disease, sponsored by NYU Langone Health. Recruiting at 1 site in United States. Open to participants aged 1 Week to 100 Years, including healthy volunteers. Per ClinicalTrials.gov, last updated 2026-06-04.

Sponsored by NYU Langone Health · Observational

From the registry’s dates

  • Started Jan 2001; still recruiting 25 years 10 months later.
Study type
Observational
Model
Family-based
Time perspective
Prospective
Enrollment
3,000
Ages
1 Week to 100 Years
Sex
All
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Study 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.

Read the 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)
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Conditions studied

  • Hirschsprung Disease

Browse trials for

Keywords

  • Hirschsprung
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In context

Hirschsprung Disease

63 studies on the registry are indexed under Hirschsprung Disease; 24 are open to participants now.

This study's planned enrollment of 3,000 is above the median of 300 across 31 observational studies indexed under Hirschsprung Disease.

Browse Hirschsprung Disease studies →

Lead sponsor

NYU Langone Health is the lead sponsor of 1,430 studies on the registry; 258 are open to participants now.

Of its 235 completed or terminated interventional studies of FDA-regulated products, 197 (84%) have results posted.

Counted across the registry records on this site, refreshed daily.

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Who can participate

Ages eligible
1 Week to 100 Years
Sexes eligible
All
Accepts healthy volunteers
Yes
Sampling method
Non-probability sample

Study population

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

Go through the criteria one by one — yes, no or not sure — and take the list to your doctor or the study team. Kept in this browser only.

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

Exclusion Criteria:

  • Unable or unwilling to provide sample for genetic studies
  • Individual, parent, or guardian unable to comprehend and provide
Terms in these criteria, in plain language(1)

Underlined terms in the criteria open these too. Explained by clinicaltrials.gg, not part of the registry record. The study team decides who can take part.

Informed consent

Before you join, the study team explains what taking part involves — its purpose, what happens, the risks and possible benefits — and answers your questions, so you can decide freely. Consent is usually recorded on a form (the informed consent form, ICF) signed by you or, where the law allows, by someone legally authorised to decide for you.

You can keep asking questions during the study, you are told of new information that matters, and you can choose to leave at any time.

05

Study design

Observational model
Family-based
Time perspective
Prospective
Enrollment
3,000 participants (estimated)
Biospecimen retention
Samples with dna

Groups and cohorts

  • Families with Hirschsprung Disease

    Individuals with Hirschsprung disease and their affected and unaffected relatives.

    Other: Identification of genetic causes of Hirschsprung Disease

Interventions

  • OtherIdentification of genetic causes of Hirschsprung Disease

    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.

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What researchers measure

Primary outcomes

  1. Discovery and characterization of common genetic variation associated with Hirschsprung disease

    Genome-wide assays of common genetic variation will be assessed using single nucleotide polymorphism (SNP) arrays

    Time frame: DNA is isolated up to 1 year after enrollment

  2. Discovery and characterization of copy number variants associated with Hirschsprung disease

    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

    Time frame: DNA is isolated up to 1 year after enrollment

  3. Discovery and characterization of rare genetic variation associated with Hirschsprung disease

    Exome sequencing will be used to detect rare variation across all genes in the genome

    Time frame: DNA is isolated up to 1 year after enrollment

Secondary outcomes

  1. Correlation of genetic variants with location of transition zone in Hirschsprung disease

    Pathology records and surgical records will be used to determine transition zone

    Time frame: Baseline pathology data is obtained up to 1 year after enrollment

  2. Correlation of genetic variants with risk for enterocolitis in Hirschsprung disease

    Time frame: Baseline clinical data is obtained up to 1 year after enrollment

  3. 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

  4. 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

  5. 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

  6. Correlation of genetic variants with need for repeat pull-through surgery in Hirschsprung disease

    Assessment of complications that lead to eventual repeat 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

  7. 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

  8. 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

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Study locations

1 of 1 sites recruiting
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References and documents

Publications

  • Badner JA, Sieber WK, Garver KL, Chakravarti A. A genetic study of Hirschsprung disease. Am J Hum Genet. 1990 Mar;46(3):568-80. PubMed 2309705 ↗
  • Emison ES, McCallion AS, Kashuk CS, Bush RT, Grice E, Lin S, Portnoy ME, Cutler DJ, Green ED, Chakravarti A. A common sex-dependent mutation in a RET enhancer underlies Hirschsprung disease risk. Nature. 2005 Apr 14;434(7035):857-63. doi: 10.1038/nature03467. PubMed 15829955 ↗
  • Gabriel SB, Salomon R, Pelet A, Angrist M, Amiel J, Fornage M, Attie-Bitach T, Olson JM, Hofstra R, Buys C, Steffann J, Munnich A, Lyonnet S, Chakravarti A. Segregation at three loci explains familial and population risk in Hirschsprung disease. Nat Genet. 2002 May;31(1):89-93. doi: 10.1038/ng868. Epub 2002 Apr 15. PubMed 11953745 ↗
  • Arnold S, Pelet A, Amiel J, Borrego S, Hofstra R, Tam P, Ceccherini I, Lyonnet S, Sherman S, Chakravarti A. Interaction between a chromosome 10 RET enhancer and chromosome 21 in the Down syndrome-Hirschsprung disease association. Hum Mutat. 2009 May;30(5):771-5. doi: 10.1002/humu.20944. PubMed 19306335 ↗
  • Emison ES, Garcia-Barcelo M, Grice EA, Lantieri F, Amiel J, Burzynski G, Fernandez RM, Hao L, Kashuk C, West K, Miao X, Tam PK, Griseri P, Ceccherini I, Pelet A, Jannot AS, de Pontual L, Henrion-Caude A, Lyonnet S, Verheij JB, Hofstra RM, Antinolo G, Borrego S, McCallion AS, Chakravarti A. Differential contributions of rare and common, coding and noncoding Ret mutations to multifactorial Hirschsprung disease liability. Am J Hum Genet. 2010 Jul 9;87(1):60-74. doi: 10.1016/j.ajhg.2010.06.007. PubMed 20598273 ↗
  • Kapoor A, Jiang Q, Chatterjee S, Chakraborty P, Sosa MX, Berrios C, Chakravarti A. Population variation in total genetic risk of Hirschsprung disease from common RET, SEMA3 and NRG1 susceptibility polymorphisms. Hum Mol Genet. 2015 May 15;24(10):2997-3003. doi: 10.1093/hmg/ddv051. Epub 2015 Feb 9. PubMed 25666438 ↗
  • Chatterjee S, Kapoor A, Akiyama JA, Auer DR, Lee D, Gabriel S, Berrios C, Pennacchio LA, Chakravarti A. Enhancer Variants Synergistically Drive Dysfunction of a Gene Regulatory Network In Hirschsprung Disease. Cell. 2016 Oct 6;167(2):355-368.e10. doi: 10.1016/j.cell.2016.09.005. Epub 2016 Sep 29. PubMed 27693352 ↗
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Updates

Tracking since Sep 25, 2026
No changes since tracking began. The registry record was last updated on Jun 4, 2026, before this site started recording changes on Sep 25, 2026. Its history is on ClinicalTrials.gov ↗
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Registry details

Key details

Study ID
NCT00478712
Lead sponsor
NYU Langone Health
Collaborators
New York University
Responsible party
Sponsor
First posted
May 25, 2007
Start date
Jan 2001
Primary completion
Dec 2028 (estimated)
Completion
Dec 2028 (estimated)
Last update
Jun 4, 2026

Study contacts

Jenna Pucel, MS, CGC
Contact
jenna.pucel@nyulangone.org
212-263-8069
Aravinda Chakravarti, PhD
principal investigator · NYU Langone Health

Oversight

Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No
View the source record on ClinicalTrials.gov ↗

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