Genetic Basis for Congenital Heart Defects: Current Knowledge

Abstract

Abstract-The intent of this review is to provide the clinician with a summary of what is currently known about the contribution of genetics to the origin of congenital heart disease. Techniques are discussed to evaluate children with heart disease for genetic alterations. Many of these techniques are now available on a clinical basis. Information on the genetic and clinical evaluation of children with cardiac disease is presented, and several tables have been constructed to aid the clinician in the assessment of children with different types of heart disease. Genetic algorithms for cardiac defects have been constructed and are available in an appendix. It is anticipated that this summary will update a wide range of medical personnel, including pediatric cardiologists and pediatricians, adult cardiologists, internists, obstetricians, nurses, and thoracic surgeons, about the genetic aspects of congenital heart disease and will encourage an interdisciplinary approach to the child and adult with congenital heart disease. (Circulation. 2007;115:3015-3038.)

Down-Klinefelter syndrome (48,XXY,+21) in a Child with Congenital Heart Disease: Case Report and Literature Review

“…However, an obvious relationship between this syndrome and CHD has not been documented, with exception of several case reports (13). In contrast, Down syndrome alone is well known for cardiac anomalies, occurring in 40% to 50% of patients (14). Freeman et al (15) reported a 44% incidence of CHD in a group of 227 infants with DS, of which 45% were atrioventricular, 35% were ventricular and 8% had an isolated atrial septal defect.…”

Genetics and Genetic Testing in Congenital Heart Disease

“…This assumption is reasonable for many inherited conditions as most mutations resulting in Mendelian disease have been traditionally detected in protein-coding regions [77][78][79] . In addition, our current ability to interpret the functional significance of variants in non-coding regions is relatively primitive 57 . Importantly, WES has been demonstrated to be both robust and cost-effective 80 , necessitating only 5% of the total sequencing required by GWS 81 .…”

The Family History: Reemergence of an Established Tool

“…While an association between CVM and genetic syndromes has been established, the appreciation of single gene defects as a cause of nonsyndromic CVM has increased substantially in recent years. Over 1000 gene tests are now clinically available including many for CVM in the context of a genetic syndrome; however, genetic testing for nonsyndromic CVM is primarily available on a research basis at this time (see http://www.genetests.org) [35,36].…”