Diaphragmatic Hernia Research & Exploration, Advancing Molecular Science

NCT ID: NCT00950118

Last Updated: 2025-12-12

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Total Enrollment

3000 participants

Study Classification

OBSERVATIONAL

Study Start Date

2005-06-30

Study Completion Date

2026-09-30

Brief Summary

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The goal of this study is to identify genes that convey susceptibility to congenital diaphragmatic hernia in humans. The identification of such genes, and examination of their structure and function, will enable a delineation of molecular pathogenesis and, ultimately, prevention or treatment of congenital diaphragmatic hernia. There are many different possible modes of inheritance for congenital anomalies, including autosomal dominant, autosomal recessive, and multifactorial. Multi-factorial inheritance is responsible for many common medical disorders, including hypertension, myocardial infarction, diabetes and cancer. This type of inheritance pattern appears to involve environmental factors as well as a combination of genetic variations that together can predispose to or produce congenital anomalies, such as congenital diaphragmatic hernia.

Our study is designed to establish a small, well-defined genetic resource consisting of 1) Nuclear families suitable for linkage analysis by parametric,non-parametric (e.g. sib pairs, TDT) and association techniques, 2) Individuals with congenital diaphragmatic hernia who can be directly screened for allelic variation in candidate genes, and 3) Individuals who can serve as controls (are unaffected by congenital diaphragmatic hernia). Neonates and their families will be collected from homogenous and heterogeneous populations. By characterizing diverse populations, it should be possible to increase the likelihood of demonstration of genetic variation in selected candidate genes that can then be used in association and linkage studies in individual subjects with congenital diaphragmatic hernia.

Detailed Description

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Congenital diaphragmatic hernia (CDH) is a birth defect that occurs when the diaphragm (thin sheet of muscle that separates the abdomen from the chest) does not form properly. When an opening is present in the diaphragm, organs that are normally in the abdomen can be pushed (herniated) through the opening and be present in the chest. Currently little is known about why this birth defect occurs.

Through this study ""Molecular Genetic Analysis of Congenital Diaphragmatic Hernia" the investigators hope to learn more about whether certain genes contribute to CDH. Genes are the instructions or blueprints for our bodies. They tell our bodies how to grow and develop. Sometimes when a mistake occurs in one or more of our genes our body does not develop properly and this can lead to a CDH. The investigators hope that the information gained through studying the genes of children with CDH and their parents, will lead to significant advances in the diagnosis, prognosis, prevention, and treatment of this disease.

Conditions

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Congenital Diaphragmatic Hernia

Study Design

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Observational Model Type

CASE_ONLY

Study Time Perspective

PROSPECTIVE

Study Groups

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Congenital Diaphragmatic Hernia (CDH)

Humans affected with congenital diaphragmatic hernia (CDH)

No interventions assigned to this group

Unaffected

Healthy family members of individuals affected with congenital diaphragmatic hernia (CDH)

No interventions assigned to this group

Eligibility Criteria

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Inclusion Criteria

* All individuals affected with a congenital diaphragmatic hernia (CDH), or with a family history of a CDH

Exclusion Criteria

* Individuals with no personal history of a CDH or family history of a family member affected with congenital diaphragmatic hernia
Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

NIH

Sponsor Role collaborator

National Institutes of Health (NIH)

NIH

Sponsor Role collaborator

Columbia University

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Yufeng Shen, PhD

Role: PRINCIPAL_INVESTIGATOR

Columbia University

Locations

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Rush Hospital

Chicago, Illinois, United States

Site Status RECRUITING

University of Michigan/ CS Mott Children's Hospital

Ann Arbor, Michigan, United States

Site Status RECRUITING

Washington University Medical Center/ St. Louis Children's Hospital

St Louis, Missouri, United States

Site Status RECRUITING

Children's Hospital of Omaha/ University of Nebraska

Omaha, Nebraska, United States

Site Status RECRUITING

Northwell Health

Manhasset, New York, United States

Site Status RECRUITING

New York University, Hassenfeld Children's Hospital at NYU Langone Health

New York, New York, United States

Site Status RECRUITING

Morgan Stanley Children's Hospital of New York- Presbyterian (Columbia University Medical Center)

New York, New York, United States

Site Status RECRUITING

Cincinnati Children's Hospital and Medical Center/ University of Cincinnati

Cincinnati, Ohio, United States

Site Status RECRUITING

Oregon Health & Science University, Doernbecher Children's Hospital

Portland, Oregon, United States

Site Status RECRUITING

Children's Hospital of Pittsburgh/ University of Pittsburgh

Pittsburgh, Pennsylvania, United States

Site Status RECRUITING

Monroe Carrell Jr Children's Hospital at Vanderbilt

Nashville, Tennessee, United States

Site Status COMPLETED

UT Southwestern Medical Center, Children's Health, Dallas

Dallas, Texas, United States

Site Status RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, United States

Site Status COMPLETED

Cairo University Hospital

Cairo, , Egypt

Site Status RECRUITING

Countries

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United States Egypt

Central Contacts

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Anah Kim Hetzler

Role: CONTACT

Facility Contacts

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Mindy Li, MD

Role: primary

Alexa Hart, MS, CGC

Role: backup

George Mychalisa, MD, MS

Role: primary

734-763-2072

Jeannie Kreutzman, RN, MSN

Role: backup

734-763-2072

Jessica Conway

Role: primary

Sheila Horak, APRN

Role: primary

Samuel Soffer, MD

Role: primary

Barbara Coons

Role: primary

Anah Kim Hetzler

Role: primary

212-342-4622

Trish Burns, BSN

Role: primary

513-803-0745

Andrew Mason

Role: primary

Elizabeth Fialkowski, MD

Role: backup

Min Shi, BSN

Role: primary

412-692-7440

Paul Waltz, MD

Role: backup

David Schindel, MD

Role: primary

214-456-6040

Mahmoud Elfiky, MD

Role: primary

201001557755

References

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Wynn J, Yu L, Chung WK. Genetic causes of congenital diaphragmatic hernia. Semin Fetal Neonatal Med. 2014 Dec;19(6):324-30. doi: 10.1016/j.siny.2014.09.003. Epub 2014 Oct 28.

Reference Type BACKGROUND
PMID: 25447988 (View on PubMed)

Pierog A, Aspelund G, Farkouh-Karoleski C, Wu M, Kriger J, Wynn J, Krishnan U, Mencin A. Predictors of low weight and tube feedings in children with congenital diaphragmatic hernia at 1 year of age. J Pediatr Gastroenterol Nutr. 2014 Oct;59(4):527-30. doi: 10.1097/MPG.0000000000000454.

Reference Type BACKGROUND
PMID: 24918983 (View on PubMed)

Yu L, Bennett JT, Wynn J, Carvill GL, Cheung YH, Shen Y, Mychaliska GB, Azarow KS, Crombleholme TM, Chung DH, Potoka D, Warner BW, Bucher B, Lim FY, Pietsch J, Stolar C, Aspelund G, Arkovitz MS; University of Washington Center for Mendelian Genomics; Mefford H, Chung WK. Whole exome sequencing identifies de novo mutations in GATA6 associated with congenital diaphragmatic hernia. J Med Genet. 2014 Mar;51(3):197-202. doi: 10.1136/jmedgenet-2013-101989. Epub 2014 Jan 2.

Reference Type BACKGROUND
PMID: 24385578 (View on PubMed)

Wynn J, Aspelund G, Zygmunt A, Stolar CJ, Mychaliska G, Butcher J, Lim FY, Gratton T, Potoka D, Brennan K, Azarow K, Jackson B, Needelman H, Crombleholme T, Zhang Y, Duong J, Arkovitz MS, Chung WK, Farkouh C. Developmental outcomes of children with congenital diaphragmatic hernia: a multicenter prospective study. J Pediatr Surg. 2013 Oct;48(10):1995-2004. doi: 10.1016/j.jpedsurg.2013.02.041.

Reference Type BACKGROUND
PMID: 24094947 (View on PubMed)

Wynn J, Krishnan U, Aspelund G, Zhang Y, Duong J, Stolar CJ, Hahn E, Pietsch J, Chung D, Moore D, Austin E, Mychaliska G, Gajarski R, Foong YL, Michelfelder E, Potolka D, Bucher B, Warner B, Grady M, Azarow K, Fletcher SE, Kutty S, Delaney J, Crombleholme T, Rosenzweig E, Chung W, Arkovitz MS. Outcomes of congenital diaphragmatic hernia in the modern era of management. J Pediatr. 2013 Jul;163(1):114-9.e1. doi: 10.1016/j.jpeds.2012.12.036. Epub 2013 Jan 30.

Reference Type BACKGROUND
PMID: 23375362 (View on PubMed)

Yu L, Wynn J, Cheung YH, Shen Y, Mychaliska GB, Crombleholme TM, Azarow KS, Lim FY, Chung DH, Potoka D, Warner BW, Bucher B, Stolar C, Aspelund G, Arkovitz MS, Chung WK. Variants in GATA4 are a rare cause of familial and sporadic congenital diaphragmatic hernia. Hum Genet. 2013 Mar;132(3):285-92. doi: 10.1007/s00439-012-1249-0. Epub 2012 Nov 9.

Reference Type BACKGROUND
PMID: 23138528 (View on PubMed)

Yu L, Wynn J, Ma L, Guha S, Mychaliska GB, Crombleholme TM, Azarow KS, Lim FY, Chung DH, Potoka D, Warner BW, Bucher B, LeDuc CA, Costa K, Stolar C, Aspelund G, Arkovitz MS, Chung WK. De novo copy number variants are associated with congenital diaphragmatic hernia. J Med Genet. 2012 Oct;49(10):650-9. doi: 10.1136/jmedgenet-2012-101135.

Reference Type BACKGROUND
PMID: 23054247 (View on PubMed)

Yu L, Sawle AD, Wynn J, Aspelund G, Stolar CJ, Arkovitz MS, Potoka D, Azarow KS, Mychaliska GB, Shen Y, Chung WK. Increased burden of de novo predicted deleterious variants in complex congenital diaphragmatic hernia. Hum Mol Genet. 2015 Aug 15;24(16):4764-73. doi: 10.1093/hmg/ddv196. Epub 2015 Jun 1.

Reference Type BACKGROUND
PMID: 26034137 (View on PubMed)

Azarow KS, Cusick R, Wynn J, Chung W, Mychaliska GB, Crombleholme TM, Chung DH, Lim FY, Potoka D, Warner BW, Aspelund G, Arkovitz MS. The association between congenital diaphragmatic hernia and undescended testes. J Pediatr Surg. 2015 May;50(5):744-5. doi: 10.1016/j.jpedsurg.2015.02.025. Epub 2015 Feb 19.

Reference Type BACKGROUND
PMID: 25783379 (View on PubMed)

Kardon G, Ackerman KG, McCulley DJ, Shen Y, Wynn J, Shang L, Bogenschutz E, Sun X, Chung WK. Congenital diaphragmatic hernias: from genes to mechanisms to therapies. Dis Model Mech. 2017 Aug 1;10(8):955-970. doi: 10.1242/dmm.028365.

Reference Type BACKGROUND
PMID: 28768736 (View on PubMed)

Kruszka P, Tanpaiboon P, Neas K, Crosby K, Berger SI, Martinez AF, Addissie YA, Pongprot Y, Sittiwangkul R, Silvilairat S, Makonkawkeyoon K, Yu L, Wynn J, Bennett JT, Mefford HC, Reynolds WT, Liu X, Mommersteeg MTM, Chung WK, Lo CW, Muenke M. Loss of function in ROBO1 is associated with tetralogy of Fallot and septal defects. J Med Genet. 2017 Dec;54(12):825-829. doi: 10.1136/jmedgenet-2017-104611. Epub 2017 Jun 7.

Reference Type BACKGROUND
PMID: 28592524 (View on PubMed)

Longoni M, High FA, Qi H, Joy MP, Hila R, Coletti CM, Wynn J, Loscertales M, Shan L, Bult CJ, Wilson JM, Shen Y, Chung WK, Donahoe PK. Genome-wide enrichment of damaging de novo variants in patients with isolated and complex congenital diaphragmatic hernia. Hum Genet. 2017 Jun;136(6):679-691. doi: 10.1007/s00439-017-1774-y. Epub 2017 Mar 16.

Reference Type BACKGROUND
PMID: 28303347 (View on PubMed)

Chiu JS, Ma L, Wynn J, Krishnan U, Rosenzweig EB, Aspelund G, Arkovitz M, Warner BW, Lim FY, Mychaliska GB, Azarow K, Cusick RA, Chung DH, Chung WK. Mutations in BMPR2 are not present in patients with pulmonary hypertension associated with congenital diaphragmatic hernia. J Pediatr Surg. 2017 Nov;52(11):1747-1750. doi: 10.1016/j.jpedsurg.2017.01.007. Epub 2017 Jan 26.

Reference Type BACKGROUND
PMID: 28162765 (View on PubMed)

Farkouh-Karoleski C, Najaf T, Wynn J, Aspelund G, Chung WK, Stolar CJ, Mychaliska GB, Warner BW, Wagner AJ, Cusick RA, Lim FY, Schindel DT, Potoka D, Azarow K, Cotten CM, Hesketh A, Soffer S, Crombleholme T, Needelman H. A definition of gentle ventilation in congenital diaphragmatic hernia: a survey of neonatologists and pediatric surgeons. J Perinat Med. 2017 Dec 20;45(9):1031-1038. doi: 10.1515/jpm-2016-0271.

Reference Type BACKGROUND
PMID: 28130958 (View on PubMed)

Abramov A, Fan W, Hernan R, Zenilman AL, Wynn J, Aspelund G, Khlevner J, Krishnan U, Lim FY, Mychaliska GB, Warner BW, Cusick R, Crombleholme T, Chung D, Danko ME, Wagner AJ, Azarow K, Schindel D, Potoka D, Soffer S, Fisher J, McCulley D, Farkouh-Karoleski C, Chung WK, Duron V. Comparative outcomes of right versus left congenital diaphragmatic hernia: A multicenter analysis. J Pediatr Surg. 2020 Jan;55(1):33-38. doi: 10.1016/j.jpedsurg.2019.09.046. Epub 2019 Oct 26.

Reference Type BACKGROUND
PMID: 31677822 (View on PubMed)

Qiao L, Wynn J, Yu L, Hernan R, Zhou X, Duron V, Aspelund G, Farkouh-Karoleski C, Zygumunt A, Krishnan US, Nees S, Khlevner J, Lim FY, Crombleholme T, Cusick R, Azarow K, Danko ME, Chung D, Warner BW, Mychaliska GB, Potoka D, Wagner AJ, Soffer S, Schindel D, McCulley DJ, Shen Y, Chung WK. Likely damaging de novo variants in congenital diaphragmatic hernia patients are associated with worse clinical outcomes. Genet Med. 2020 Dec;22(12):2020-2028. doi: 10.1038/s41436-020-0908-0. Epub 2020 Jul 28.

Reference Type BACKGROUND
PMID: 32719394 (View on PubMed)

Yu L, Hernan RR, Wynn J, Chung WK. The influence of genetics in congenital diaphragmatic hernia. Semin Perinatol. 2020 Feb;44(1):151169. doi: 10.1053/j.semperi.2019.07.008. Epub 2019 Aug 1.

Reference Type BACKGROUND
PMID: 31443905 (View on PubMed)

Related Links

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Other Identifiers

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R01HD057036

Identifier Type: NIH

Identifier Source: secondary_id

View Link

AAAB2063

Identifier Type: -

Identifier Source: org_study_id

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