Current Environment:


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.


Heart Disease Congenital

Recruitment Status


Eligibility Criteria

Inclusion Criteria:

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

Exclusion Criteria:

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


Intervention Type

Intervention Name


Exposure of interest: Brain MRI


Exposure of interest: neurodevelopmental assessments



Min Age

8 Years

Max Age


Download Date

August 13, 2020

Principal Investigator


Primary Contact Information

For more information on this trial, visit


For more information and to contact the study team:

Genomic Basis of Neurodevelopmental and Brain Outcomes in Congenital Heart Disease (CHD Brain and Genes) NCT03070197