Genetics of Congenital Heart Disease
Is the Glass Now Half-Full?
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Congenital heart defects are present in 1% of all live births and are a significant burden on the parents and family, healthcare system, and overall community. Congenital heart defects (CHD) are also identified in 10% of still births and are presumed to be a substantial cause of early fetal demise. With advances in prenatal diagnosis, corrective strategies, and longitudinal care, infant mortality has substantially declined. Today >75% of CHD children who survive the first year of live will enter into adulthood. Elucidating the cause of an offspring’s CHD is greatly valued by parents, providing comfort that the defect was because of genetic randomness beyond their control and that certain problems arise from the same underlying genetic issue and not from preventable errors.1 As Helen Taussig stated 50 years ago “Our next great step forward will come in the field of cause and prevention of malformations.”2 Causes of CHD are often divided into genetic and nongenetic influences. The advantage of contemporary genomic technologies including single-nucleotide polymorphism (SNP) arrays, next-generation sequencing, and copy-number variant platforms are accelerating the discovery of genetic causes of CHD. Importantly, these tools enable the study of sporadic cases, the most common presentation of CHD. A review article summarizing this field entitled the “Genetics of Congenital Heart Disease: The Glass Half-Empty” previously highlighted the limitations of genetic technologies for assigning causality.3 Articles such as the present one in this journal entitled “Genome-Wide Association Studies and Meta-analysis for Congenital Heart Defects”4 are important studies performed using distinct patient cohorts from multiple sites. We are now looking for the complex multigenetic explanations for CHD in a multifactorial scheme, including epigenetic and environmental factors. There is renewed optimism in the field such that today we would see the genetics of CHD but hopefully now with the …