Genotype-Phenotype Associations in Pediatric Cardiomyopathy (PCM GENES)
|Dilated Cardiomyopathy Hypertrophic Cardiomyopathy Restrictive Cardiomyopathy|
|Study Design:||Observational Model: Cohort
Time Perspective: Prospective
|Official Title:||Genotype-Phenotype Associations in Pediatric Cardiomyopathy|
- Time to death [ Time Frame: 2 years ]
- Time to transplant [ Time Frame: 2 years ]
- Time to normalized left ventricular size or function in dilated cardiomyopathy [ Time Frame: 2 years ]
- Septal:Posterior wall thickness ratio in hypertrophic cardiomyopathy [ Time Frame: 2 years ]
- Left ventricular outflow tract in hypertrophic cardiomyopathy [ Time Frame: 2 years ]
Biospecimen Retention: Samples With DNA
|Study Start Date:||April 2013|
|Estimated Study Completion Date:||March 2017|
|Primary Completion Date:||February 2017 (Final data collection date for primary outcome measure)|
Diagnosis of primary or idiopathic dilated, hypertrophic or restrictive cardiomyopathy. Diagnosis must have been made before the age of 18 and must be confirmed by established echocardiographic criteria or cardiac MRI (cMRI) at the time of diagnosis.
Pediatric cardiomyopathy is a heterogeneous genetic disease with high morbidity and mortality in which children often present with fulminant disease leading to death or transplant. The long-term goal of this project is to identify the genetic basis of cardiomyopathy and to correlate these findings with clinical phenotypes for risk stratification. These findings could improve disease prevention, surveillance, early management, and prognosis.
The specific aims of this study are:
- To identify the disease-causing and disease-associated genetic variants underlying pediatric cardiomyopathy in a carefully phenotyped cohort.
- To identify genotype-phenotype correlations that allow for risk stratification and improve management and therapy.
Exome sequencing will be used as part of a tiered genetic analysis in a large cohort of up to 700 pediatric cardiomyopathy subjects with systolic (dilated cardiomyopathy) or diastolic (hypertrophic or restrictive cardiomyopathy) dysfunction. The biological parent(s) of enrolled participants will also be approached about participating and providing a blood sample for genetic testing. In addition to the parent(s), the participants siblings and other relatives may also be approached regarding enrollment, based on the pedigree and family history.
This study will significantly increase our understanding of pediatric cardiomyopathy by defining the prevalence of mutations in genes known to cause cardiomyopathy as well as identifying novel disease-causing genes in the pediatric population. Genetic association tests will identify variants that modify disease. Novel bioinformatics and systems biology applications for interpretation of exome level genetic information will contribute fundamental knowledge and technical innovation to the translation of genomic data to clinical utility. These aims will provide critical genetic architecture data, identify variants with large effects, and enable genotype-phenotype correlations necessary for advancing management and therapy.
The Study will have two components: 1) clinical data collection by chart review and family interview, and 2) biospecimen collection and genetic testing.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01873963
|United States, Colorado|
|Children's Hospital Colorado|
|Aurora, Colorado, United States, 80045|
|United States, Florida|
|University of Miami, Jackson Memorial Hospital|
|Miami, Florida, United States, 33136|
|United States, Illinois|
|Ann and Robert H. Lurie Children's Hospital of Chicago|
|Chicago, Illinois, United States, 60611|
|United States, Massachusetts|
|Children's Hospital Boston|
|Boston, Massachusetts, United States, 02115|
|United States, Missouri|
|Washington University School of Medicine|
|St. Louis, Missouri, United States, 63110|
|United States, New York|
|Children's Hospital at Montefiore|
|Bronx, New York, United States, 10467|
|Children's Hospital of New York, Columbia Presbyterian Medical Center|
|New York, New York, United States, 10032|
|United States, Ohio|
|Cincinnati Children's Hospital Medical Center|
|Cincinnati, Ohio, United States, 45229|
|United States, Pennsylvania|
|Children's Hospital of Philadelphia|
|Philadelphia, Pennsylvania, United States, 19104|
|United States, Tennessee|
|Monroe Carell Jr. Children's Hospital at Vanderbilt|
|Nashville, Tennessee, United States, 37232|
|United States, Utah|
|Primary Children's Medical Center|
|Salt Lake City, Utah, United States, 84113|
|Stollery Children's Hospital|
|Edmonton, Alberta, Canada, T6G 2B7|
|Principal Investigator:||Steven E Lipshultz, MD||Wayne State University|