Hirschsprung DiseaseNCT00478712
Hirschsprung Disease Genetic Study
An observational study of Hirschsprung Disease, run by NYU Langone Health at 1 site in United States.
Trial 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 more about this study
- Who is it for?
- Ages 1 week to 100 yearsHealthy volunteers can take part
- Conditions the study is for
- Hirschsprung Disease
- What is being tested?
- Identification of genetic causes of Hirschsprung Disease
- How many people
- 3,000 participants
- Where
- 1 siteUnited States
- Study dates
- Jan 2001to Dec 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 1 week to 100 years
- All sexes
- Healthy volunteers accepted
- Child, Adult, Older adult
Study population: The study population includes individuals with Hirschsprung disease and their family members.
Who may be able to join
- 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)
Who cannot join
- Unable or unwilling to provide sample for genetic studies
- Individual, parent, or guardian unable to comprehend and provide informed consent
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
United States1 site, 1 recruiting
- Recruiting
New York University School of Medicine
New York, New York, 10016
Monica Erazo, MS, 212-263-8069, Monica.Erazo@nyulangone.org
Aravinda Chakravarti, PhD
About this study
Official title: 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.
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:
- Complete a medical/family history questionnaire
- Provide access to some medical records
- Submit blood samples from the individual(s) affected with Hirschsprung disease and his/her parents (if available)
- Conditions
- Hirschsprung Disease
- Being tested
- Identification of genetic causes of Hirschsprung Disease
- Keywords
- Hirschsprung
- Medical subject headings
- Hirschsprung Disease
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Identification of genetic causes of Hirschsprung DiseaseOther
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.
| Study group | Role | What they receive |
|---|---|---|
| Families with Hirschsprung Disease | Individuals with Hirschsprung disease and their affected and unaffected relatives. Receives: Other: Identification of genetic causes of Hirschsprung Disease |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: DNA is isolated up to 1 year after enrollment
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
Measured: DNA is isolated up to 1 year after enrollment
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
Measured: DNA is isolated up to 1 year after enrollment
Secondary outcomes (8)
Correlation of genetic variants with location of transition zone in Hirschsprung disease
Pathology records and surgical records will be used to determine transition zone
Measured: Baseline pathology data is obtained up to 1 year after enrollment
Correlation of genetic variants with risk for enterocolitis in Hirschsprung disease
Measured: Baseline clinical data is obtained up to 1 year after enrollment
Characterization of Hirschsprung disease that co-occurs with a known chromosomal disorder
Measured: Baseline clinical data is obtained up to 1 year after enrollment
Characterization of Hirschsprung disease that co-occurs with a known single gene syndrome
Measured: 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
Measured: 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
Assessment of complications that lead to eventual repeat pull-through surgery
Measured: 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
Measured: 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
Measured: Baseline clinical data is obtained up to 1 year after enrollment and follow up data is obtained up to 100 years after enrollment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 May 2007 (estimated)
- Study startJan 2001
- Primary completionDec 2028 (estimated)
- Study completionDec 2028 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Hirschsprung DiseaseStudies of the same condition, open and under way.
- More trials run by NYU Langone HealthThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Family based
- Time perspective
- Prospective
- Enrolment
- 3,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- NYU Langone Health
- Sponsor type
- University, hospital or other
- Collaborators
- New York University
- Responsible party
- Sponsor
- Investigators
- Aravinda Chakravarti, PhD, Principal investigator, NYU Langone Health
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00478712
- Sponsor's protocol ID
- 17-01813
- Status last verified
- Jun 2026
- First submitted
- 24 May 2007
- Last updated
- 4 Jun 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
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 2309705Emison 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 15829955Gabriel 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 11953745Arnold 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 19306335Emison 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 20598273Kapoor 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 25666438Chatterjee 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
Study at a glance
From the registry record, last updated by the sponsor on 4 Jun 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Genetic Analysis of Hirschsprung Disease
- ClinicalTrials.gov ID
- NCT00478712
- Acronym / sponsor ID
- 17-01813
- Conditions
- Hirschsprung Disease
- Keywords
- Hirschsprung
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 3,000 participants (estimated)
- Lead sponsor
- NYU Langone HealthUniversity, hospital or other
- Collaborators
- New York University
- Study start
- Jan 2001 (actual)
- Primary completion
- Dec 2028 (estimated)
- Study completion
- Dec 2028 (estimated)
- First posted
- 25 May 2007 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 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:
- Complete a medical/family history questionnaire
- Provide access to some medical records
- Submit blood samples from the individual(s) affected with Hirschsprung disease and his/her parents (if available)
Study design
- Observational model
- Family based
- Time perspective
- Prospective
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Families with Hirschsprung Disease | – | Other: Identification of genetic causes of Hirschsprung DiseaseIndividuals with Hirschsprung disease and their affected and unaffected relatives. |
Who may qualify
- Ages
- 1 week to 100 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Child, Adult, Older adult
- Study population
- The study population includes individuals with Hirschsprung disease and their family members.
Key inclusion criteria (1 listed)
- 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)
Key exclusion criteria (2 listed)
- Unable or unwilling to provide sample for genetic studies
- Individual, parent, or guardian unable to comprehend and provide informed consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Identification of genetic causes of Hirschsprung DiseaseBlood, 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. | Other | Families with Hirschsprung Disease |
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
8 secondary outcomes
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
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
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
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 4 Jun 2026.
- Background: PubMed 2309705Badner JA, Sieber WK, Garver KL, Chakravarti A. A genetic study of Hirschsprung disease. Am J Hum Genet. 1990 Mar;46(3):568-80.
- Results publication: PubMed 15829955Emison 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.
- Results publication: PubMed 11953745Gabriel 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.
- Results publication: PubMed 19306335Arnold 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.
- Results publication: PubMed 20598273Emison 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.
- Results publication: PubMed 25666438Kapoor 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.
- Results publication: PubMed 27693352Chatterjee 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.
- Chakravarti, Johns Hopkins Medical Institution (JHMI) Faculty Biography PageLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Aravinda Chakravarti, PhD principal investigator
NYU Langone Health
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Hirschsprung Disease, run by NYU Langone Health at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 2 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 4 Jun 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jenna Pucel, MS, CGC (212-263-8069, jenna.pucel@nyulangone.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Discovery and characterization of common genetic variation associated with Hirschsprung disease (time frame: DNA is isolated up to 1 year after enrollment). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00478712, which also lists 7 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 4 Jun 2026.