Genomic Basis of Neurodevelopmental and Brain Outcomes in Congenital Heart Disease (CHD Brain and Genes)
- Conditions
- Heart Disease Congenital
- Registration Number
- NCT03070197
- Lead Sponsor
- Children's Hospital Medical Center, Cincinnati
- Brief Summary
Approximately 400 Congenital heart disease patients will participate in the research study which will include one or more research visits for neurodevelopmental testing, brain MRI, and collection of medical history including previously collected genetic sequencing results. The investigators will explore the association between genetic variants, neurodevelopmental deficits, and brain MRI endophenotype. Analyses will compare groups with and without deleterious de novo mutations.
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 196
- Subjects in whom whole exome sequencing or whole genome sequencing has already been performed, either during the CHD GENES study or, for new centers (Utah or USCF/Stanford), after trios in existing biobanks undergo analysis by whole exome sequencing or whole genome sequencing during the Pediatric Cardiac Genomic Consortium 2 grant cycle
- Presence of deleterious mutations (damaging de novo mutations or stringently defined deleterious missense mutations) identified on sequencing (Cases) OR absence of such known deleterious mutations (Controls)
- Males or females, age ≥8 years
- Diagnosis of congenital heart disease
- Informed consent obtained
- History of cardiac transplant
- A cardiac surgical procedure within 6 months of enrollment
- Known clinical genetic syndrome, characterized as a monogenic condition with an identified gene associated with abnormalities of the brain structure or function, structural heart disease, and potentially other associated features.
- Presence of CNV known to be clinically pathogenic. Variants will be classified as pathogenic using accepted types of variant evidence (e.g., population data, computational data, functional data, segregation data) as detailed in the American College of Medical Genetics and Genomics " Standards and Guidelines for the interpretation of sequence variants" (Richards et al, GIM 2015).
- Overwhelming acquired brain injury, such as a major stroke or severe ischemic injury, that would overshadow the effect of a genetic mutation on outcome in the opinion of the center investigator
- Lack of reading fluency in English or Spanish
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method Neurodevelopment and behavioral health assessment Day 1 The investigators will compare groups with respect to achievement, IQ, learning disability, specific neuropsychological domains (e.g., memory, attention, executive functions, and visual-spatial/motor integration), adaptive function, behavior, social cognition and symptoms of autism spectrum disorder, and quality of life. The primary study outcome for this aim will be the WRAT4 composite score.
- Secondary Outcome Measures
Name Time Method Abnormalities in brain structure and microstructure on MRI Day 1 The investigators will compare the groups with respect to measured and derived parameters including, but not limited to, 1) regional volumetric and cortical thickness, 2) regional surface metrics, 3) voxel-based DTI eigenvectors and apparent diffusion coefficient (ADC) values, and resting state principal component analysis
Trial Locations
- Locations (8)
Children's Hospital Philadelphia
🇺🇸Philadelphia, Pennsylvania, United States
Icahn School of Medicine at Mt. Sinai
🇺🇸New York, New York, United States
University of Rochester
🇺🇸Rochester, New York, United States
Children's Hospital Los Angeles
🇺🇸Los Angeles, California, United States
University of California, San Francisco
🇺🇸San Francisco, California, United States
Yale University
🇺🇸New Haven, Connecticut, United States
Children's Hospital Boston
🇺🇸Boston, Massachusetts, United States
University of Utah
🇺🇸Salt Lake City, Utah, United States