Congenital Heart Disease: The Crossroads of Genetics, Epigenetics and Environment

Abstract

Congenital heart diseases (CHDs) are recognized as the most common type of birth malformations. Although recent advances in pre- and neonatal diagnosis as well as in surgical procedures have reduced the morbidity and mortality for many CHD, the etiology for CHD remains undefined. In non-syndromic and isolated (without a familial history or a Mendelian inheritance) forms of CHDs, a multifactorial pathogenesis with interplay between inherited and non-inherited causes is recognized. In this paper, we discuss the current knowledge of the potential molecular mechanisms, mediating abnormal cardiac development in non-syndromic and isolated CHD, including mutations in cardiac transcription factors, the role of somatic mutations and epigenetic alterations as well as the influence of gene-environment interactions. In the near future, the advent of high-throughput genomic technologies with the integration of system biology will expand our understanding of isolated, non-syndromic CHDs for their prevention, early diagnosis and therapy.

Pediatric Heart Conditions: What Do Occupational Therapists Need to Know?

“…Congenital heart disease (CHD) is the most diagnosed congenital anomaly occurring in approximately 1 out of every 110 live births. CHD has a substantial (30%) genetic component (Ko, 2015), but the cause remains speculative with epigenetic factors a strong consideration (Vecoli et al, 2014). One quarter of those diagnosed are considered critical and will need immediate surgery within hours or days of birth (American Heart Association [AHA], 2019).…”

Understanding the epigenetic origins of congenital heart disease may lead to its control

“…(24) Since the BWIS, many extensive studies of nongenetic (environmental) factors influencing the incidence of CHD have been performed. (25) Patel and Burns (26) summarised these in a metaanalysis in 2013. Figure 3 summarises the most significant environmental factors from their study in terms of the most significant odds ratios for the risk of CHD.…”

Analyses of trends in prevalence of congenital heart defects and folic acid supplementation

“…These costs extend beyond childhood as children with CHD are now surviving well into later decades in life (6). Most CHDs are thought to be multifactorial in origin, involving genetic and environmental factors (7)(8)(9)(10). Despite notable contributions of epidemiologic research in the discovery of the etiology of these defects, the number of modifiable risk factors identified has been limited: including maternal pre-pregnancy diabetes, exposure to certain medications or maternal infections (e.g., rubella), uncontrolled maternal phenylketonuria, and possibly maternal pre-pregnancy obesity, smoking, and consanguinity (8,11).…”