Clinical trial NCT00950118: Diaphragmatic Hernia Research & Exploration, Advancing Molecular Science
Official title: Diaphragmatic Hernia Research & Exploration, Advancing Molecular Science
Study type: OBSERVATIONAL
Overall status: RECRUITING
Conditions: Congenital Diaphragmatic Hernia
Keywords: Congenital Diaphragmatic Hernia (CDH)
Genes
Genetic
Genetic testing
exome sequencing
genome sequencing
RNAseq
Lead sponsor: Columbia University
Sponsor class: OTHER
Collaborators: name: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
name: National Institutes of Health (NIH)
First posted: 2009-07-31
Enrollment: 3000
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Observational model: CASE_ONLY
Time perspective: PROSPECTIVE
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

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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Percentage of patients with a genetic diagnosis
timeFrame: 5 years
Secondary outcomes:
measure: Developmental outcomes at 2 and 5 years of age
timeFrame: 1 exam at 2 year and 1 exam at 5 years
measure: Percentage of patients with pulmonary hypertension
timeFrame: 5 years
Other outcomes:
Locations:
city: Chicago
country: United States
facility: Rush Hospital
state: Illinois
city: Ann Arbor
country: United States
facility: University of Michigan/ CS Mott Children's Hospital
state: Michigan
city: Saint Louis
country: United States
facility: Washington University Medical Center/ St. Louis Children's Hospital
state: Missouri
city: Omaha
country: United States
facility: Children's Hospital of Omaha/ University of Nebraska
state: Nebraska
city: Manhasset
country: United States
facility: Northwell Health
state: New York
city: New York
country: United States
facility: New York University, Hassenfeld Children's Hospital at NYU Langone Health
state: New York
city: New York
country: United States
facility: Morgan Stanley Children's Hospital of New York- Presbyterian (Columbia University Medical Center)
state: New York
city: Cincinnati
country: United States
facility: Cincinnati Children's Hospital and Medical Center/ University of Cincinnati
state: Ohio
city: Portland
country: United States
facility: Oregon Health & Science University, Doernbecher Children's Hospital
state: Oregon
city: Pittsburgh
country: United States
facility: Children's Hospital of Pittsburgh/ University of Pittsburgh
state: Pennsylvania
city: Nashville
country: United States
facility: Monroe Carrell Jr Children's Hospital at Vanderbilt
state: Tennessee
city: Dallas
country: United States
facility: UT Southwestern Medical Center, Children's Health, Dallas
state: Texas
city: Milwaukee
country: United States
facility: Medical College of Wisconsin
state: Wisconsin
city: Cairo
country: Egypt
facility: Cairo University Hospital
Study officials:
affiliation: Columbia University
name: Yufeng Shen, PhD
role: PRINCIPAL_INVESTIGATOR
References:
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