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

  • Study HIC#:2000020449
  • Last Updated:07/15/2021

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.

  • Age8 years and older
  • GenderBoth
  • Start Date10/23/2017
  • End Date12/31/2027

Trial Purpose and Description

Approximately 400 CHD patients will participate in the research study which will include 1 or more research visits for neurodevelopmental testing, brain MRI, and collection of medical history including previously collected genetic sequencing results. Administrative and Data Coordinating Center (ACC/DCC): Cincinnati Children’s Hospital Medical Center (CCHMC). 1. To compare neurodevelopmental and behavioral health outcomes in individuals with CHD who have deleterious mutations (damaging de novo mutations or stringently defined deleterious missense mutations) on whole exome sequencing (WES) or whole genome sequencing (WGS) vs. those without such variants. 2. To compare abnormalities in brain structure and microstructure on MRI in individuals with CHD who have deleterious mutations on WES or WGS vs. those without any variants

Eligibility Criteria

Study Population Congenital heart disease patients aged 8 years and older with prior whole exome sequencing or whole genome sequencing results 


Inclusion Criteria: 

1.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 

2.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) 

3.Males or females  age 8 years and older  

4.Diagnosis of congenital heart disease 5.Informed consent obtained 


Exclusion Criteria: 

1.History of cardiac transplant 

2.A cardiac surgical procedure within 6 months of enrollment 

3.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. 

4.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 6.Lack of reading fluency in English or Spanish 

Sub-Investigators

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