Diaphragmatic Hernia Research & Exploration, Advancing Molecular Science

Study Overview
=================
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.

Official Title
-----------------
Diaphragmatic Hernia Research & Exploration, Advancing Molecular Science

Conditions
-----------------
Congenital Diaphragmatic Hernia

Participation Criteria
=================
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
Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Congenital Diaphragmatic Hernia (CDH)<br>Humans affected with congenital diaphragmatic hernia (CDH) | |
| Unaffected<br>Healthy family members of individuals affected with congenital diaphragmatic hernia (CDH) | |

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of patients with a genetic diagnosis | DNA samples from patients will be analyzed for underlying genetic causes. | 5 years | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Developmental outcomes at 2 and 5 years of age | Formal Developmental outcome measures | 1 exam at 2 year and 1 exam at 5 years | 
| Percentage of patients with pulmonary hypertension | pulmonary hypertension measured by echocardiogram | 5 years | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Congenital Diaphragmatic Hernia (CDH), Genes, Genetic, Genetic testing, exome sequencing, genome sequencing, RNAseq