Diaphragmatic Hernia Research & Exploration, Advancing Molecular Science

NCT00950118 | Recruiting

• 2 other identifiers: AAAB2063R01HD057036
• Study Type: observational
• Target: 3,000
• Locations: 2 countries
• Sites: 14

Brief Summary

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.

Conditions

Congenital Diaphragmatic Hernia

Keywords

Congenital Diaphragmatic Hernia (CDH); Genes; Genetic; Genetic testing; exome sequencing; genome sequencing; RNAseq

Outcome Measures

Primary Outcomes (1)

• Percentage of patients with a genetic diagnosis

  DNA samples from patients will be analyzed for underlying genetic causes.

  5 years

Secondary Outcomes (2)

• Developmental outcomes at 2 and 5 years of age

  1 exam at 2 year and 1 exam at 5 years

• Percentage of patients with pulmonary hypertension

  5 years

Study Arms (2)

Congenital Diaphragmatic Hernia (CDH)

Humans affected with congenital diaphragmatic hernia (CDH)

Unaffected

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

Eligibility Criteria

• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Probability Sample

Study Population

Children/neonates with an unrepaired congenital diaphragmatic hernia Children/neonates with a reparied congenital diaphragmatic hernia Women who are pregnant with a fetus diagnosed with congenital diaphragmatic hernia Individuals with a family history of congenital diaphragmatic hernia

You may qualify if:

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

You may not qualify if:

• Individuals with no personal history of a CDH or family history of a family member affected with congenital diaphragmatic hernia

Sponsors & Collaborators

• Columbia University: lead
• Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD): collaborator
• National Institutes of Health (NIH): collaborator

Study Sites (14)

Rush Hospital

Chicago, Illinois, 60612, United States

RECRUITING

University of Michigan/ CS Mott Children's Hospital

Ann Arbor, Michigan, 48167-5245, United States

RECRUITING

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

St Louis, Missouri, 63110, United States

RECRUITING

Children's Hospital of Omaha/ University of Nebraska

Omaha, Nebraska, 68114, United States

RECRUITING

Northwell Health

Manhasset, New York, 11030, United States

RECRUITING

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

New York, New York, 10016, United States

RECRUITING

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

New York, New York, 10032, United States

RECRUITING

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

Cincinnati, Ohio, 45229, United States

RECRUITING

Oregon Health & Science University, Doernbecher Children's Hospital

Portland, Oregon, 97239, United States

RECRUITING

Children's Hospital of Pittsburgh/ University of Pittsburgh

Pittsburgh, Pennsylvania, 15213, United States

RECRUITING

Monroe Carrell Jr Children's Hospital at Vanderbilt

Nashville, Tennessee, 37232, United States

COMPLETED

UT Southwestern Medical Center, Children's Health, Dallas

Dallas, Texas, 75235, United States

RECRUITING

Medical College of Wisconsin

Milwaukee, Wisconsin, 53226, United States

COMPLETED

Cairo University Hospital

Cairo, Egypt

RECRUITING

Related Publications (17)

• 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.

  PMID: 25447988 BACKGROUND

• 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.

  PMID: 24918983 BACKGROUND

• 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.

  PMID: 24385578 BACKGROUND

• 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.

  PMID: 24094947 BACKGROUND

• 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.

  PMID: 23375362 BACKGROUND

• 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.

  PMID: 23138528 BACKGROUND

• 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.

  PMID: 23054247 BACKGROUND

• 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.

  PMID: 26034137 BACKGROUND

• 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.

  PMID: 25783379 BACKGROUND

• 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.

  PMID: 28768736 BACKGROUND

• 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.

  PMID: 28592524 BACKGROUND

• 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.

  PMID: 28303347 BACKGROUND

• 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.

  PMID: 28162765 BACKGROUND

• 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.

  PMID: 28130958 BACKGROUND

• 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.

  PMID: 31677822 BACKGROUND

• 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.

  PMID: 32719394 BACKGROUND

• 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.

  PMID: 31443905 BACKGROUND

Related Links

• Study Website

Biospecimen

Retention: SAMPLES WITH DNA

whole blood, tissue, saliva

MeSH Terms

Conditions

Hernias, Diaphragmatic, Congenital

Condition Hierarchy (Ancestors)

Congenital Abnormalities; Congenital, Hereditary, and Neonatal Diseases and Abnormalities; Hernia, Diaphragmatic; Internal Hernia; Hernia; Pathological Conditions, Anatomical; Pathological Conditions, Signs and Symptoms

Study Officials

• Yufeng Shen, PhD

  Columbia University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Anah Kim Hetzler

CONTACT

ak3578@columbia.edu

Study Design

• Study Type: observational
• Observational Model: CASE ONLY
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 29, 2009
• First Posted: July 31, 2009
• Study Start: June 1, 2005
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: December 12, 2025

Record last verified: 2025-12

Locations

US (13); EG (1)