Recent dramatic improvements in the survival of patients with congenital heart disease (CHD) have been accompanied by the recognition that this population manifests a high prevalence of neurologic and developmental abnormalities. Tetralogy of Fallot (TOF) comprises approximately 8 to 10% of all congenital heart lesions. This lesion alone presents a population of over 50,000 children who are at risk for neurocognitive and mental health deficits. We propose to evaluate a cohort with TOF at ages 13 through 17 years, compared to a group of adolescents in the general population frequency matched for age and gender.
Aim 1 is to compare TOF and control groups on academic achievement, cognition and behavior. The primary outcome will be Total Composite Score on the Wechsler Individual Achievement Test. Secondary outcomes will include measures of ability (IQ), learning disability, neuropsychologic function (i.e., language, memory, attention, executive functions, and visual-spatial/motor integration) and mental health, including quality-of-life and global emotional functioning, as well as specific psychiatric diagnoses, including mood, anxiety, attention-deficit/disruptive behavior and psychotic disorders.
Aim 2 is to compare TOF and control groups on measures of brain structure. The primary outcome using quantitative volumetric MRI imaging and seqmentation will be total brain tissue volume. Secondary outcomes will be volumes of gray matter (total, cortical, and subcortical gray matter), white matter (myelinated and unmyelinated white matter), and cerebrospinal fluid. The primary outcome using diffusion tensor MRI imaging will be reqional white matter microstructure, as measured by relative anisotropy (RA). Secondary outcomes will include regional apparent diffusion coefficients.
Aim 3 is to compare TOF and control groups on measures of brain function. The primary outcome will be the activation map derived from performance of a visuospatial working memory task by using functional MRI.
Aim 4 examines the relationship of TOF disease genes, both known and newly-discovered in Project 3, to development, brain structure, and brain function (i.e., genotype-phenotype correlation). These studies will establish, with greater clarity and specificity, the nature and basis of neurodevelopmental sequelae of TOF.
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