The Evolving Landscape of CHD Genetics: A Contemporary Guide to Genetic Testing and Management.

Abstract

Congenital heart disease (CHD) is the most common birth defect, affecting an estimated 9.4/1000 infants globally. The genetics of CHD is complex, with most cases thought to have multifactorial aetiology, implicating both genetic and environmental factors. Over the last decade, advances in genomic technologies have enabled significant discoveries in the field, with over 170 genes associated with human CHD to date. Further, the diagnostic yield in some patient subgroups is now comparable with other monogenic diseases such that genetic testing is increasingly part of routine CHD care with greater clinical utility. In line with these advances, genetic testing recommendations have been developed to inform and facilitate appropriate genetic testing in CHD patients, including who, when, why, and how to test. In this review, we explore the current understanding of the CHD genetics landscape and how this has evolved, also with respect to the often-evidenced comorbidities present in many patients, including those with syndromic presentations. We discuss practical considerations of genetic testing in CHD, including the type and timing of the testing, diagnostic yields across specific patient groups, patients most likely to benefit from the testing, psychosocial impacts, and the broader implications on clinical care and management. Further, we outline the value and utility of genetic testing for patients and families in line with our experience at the first paediatric CHD genetic clinic in Australia. Finally, we explore future directions for genetic testing in CHD, including the applicability and appropriateness of universal genetic testing in the prenatal and neonatal setting.