Congenital heart diseases: genetics, non-inherited risk factors, and signaling pathways

Abstract

Background: Congenital heart diseases (CHDs) are the most common congenital anomalies with an estimated prevalence of 8 in 1000 live births. CHDs occur as a result of abnormal embryogenesis of the heart. Congenital heart diseases are associated with significant mortality and morbidity. The damage of the heart is irreversible due to a lack of regeneration potential, and usually, the patients may require surgical intervention. Studying the developmental biology of the heart is essential not only in understanding the mechanisms and pathogenesis of congenital heart diseases but also in providing us with insight towards developing new preventive and treatment methods. Main body: The etiology of congenital heart diseases is still elusive. Both genetic and environmental factors have been implicated to play a role in the pathogenesis of the diseases. Recently, cardiac transcription factors, cardiacspecific genes, and signaling pathways, which are responsible for early cardiac morphogenesis have been extensively studied in both human and animal experiments but leave much to be desired. The discovery of novel genetic methods such as next generation sequencing and chromosomal microarrays have led to further study the genes, non-coding RNAs and subtle chromosomal changes, elucidating their implications to the etiology of congenital heart diseases. Studies have also implicated non-hereditary risk factors such as rubella infection, teratogens, maternal age, diabetes mellitus, and abnormal hemodynamics in causing CHDs. These etiological factors raise questions on multifactorial etiology of CHDs. It is therefore important to endeavor in research based on finding the causes of CHDs. Finding causative factors will enable us to plan intervention strategies and mitigate the consequences associated with CHDs. This review, therefore, puts forward the genetic and non-genetic causes of congenital heart diseases. Besides, it discusses crucial signaling pathways which are involved in early cardiac morphogenesis. Consequently, we aim to consolidate our knowledge on multifactorial causes of CHDs so as to pave a way for further research regarding CHDs. Conclusion: The multifactorial etiology of congenital heart diseases gives us a challenge to explicitly establishing specific causative factors and therefore plan intervention strategies. More well-designed studies and the use of novel genetic technologies could be the way through the discovery of etiological factors implicated in the pathogenesis of congenital heart diseases.

Bisphenols and phthalates: Plastic chemical exposures can contribute to adverse cardiovascular health outcomes

“…Tang et al reported that maternal DEHP exposure (250 mg/ kg-1 g/kg) led to congenital heart defects and altered the expression of key cardiac transcription factors in mice (MEF2C, GATA4, CHF1) (Tang et al, 2018). These transcription factors are essential to cardiac development and the expression of sarcomere genes (Estrella & Naya, 2014;Suluba, Shuwei, Xia, & Mwanga, 2020). Of interest, Wang et al reported that parental occupational exposure to phthalates was associated with an increased risk of congenital heart defects, including patent ductus arteriosus, atrial and ventricular septal defects (C. Wang et al, 2015).…”

Research on Congenital Heart Defects: A Bibliometric Assessment of India’s Publications during 2000-19

“…Gene mutations and some teratogens can interfere with normal development (embryogenesis) of the heart leading to congenital heart defects. 3 Studies have also implicated non-hereditary risk factors such as rubella infection, teratogens, maternal age, diabetes mellitus, abnormal hemodynamics use of certain medications or drugs such as alcohol or tobacco, parents being closely related or poor nutritional status or obesity in the mother, besides having a parent with a congenital heart defect is also a risk factor in causing CHDs. 3,4 The most common CHD including left-to-right shunts (atrial septal defect, ventricular septal defect, atrioventricular septal defect, patent ductus arteriosus and others), obstructive lesions (pulmonary stenosis, aortic stenosis and coarctation of aorta) and cyanotic CHD (tetralogy of Fallot, transposition of great arteries, univentricular hearts, total anomalous pulmonary venous connection, Ebstein's anomaly and others).…”

“…Therefore, cyanotic congenital heart defects are regarded as the most severe forms of CHDs. 3 Clinical presentations and severity of CHDs depend on their types or sub-types. However, most children with CHDs present with failure to thrive, cough, repeated chest infections, difficulty in breathing, exercise intolerance and bluish discoloration of mucous membranes (cyanosis).…”

“…Congenital heart defects are associated with serious complications such as cognitive impairment and often affect families and individuals both emotionally and financially. 3,4 Diagnostic and treatment capabilities for congenital heart disease have dramatically improved over the past. Many studies show substantial improvement in survival in developed regions of the world, but the same success rates are not yet seen in developing regions.…”

“…03% (1322) of CHD research in India appeared in 209 journals, 0.60%(8) in conference proceedings, 0.22%(3) in book series and 0.15% (2) as books. Of the 209 journals (reporting 1325 articles), 184 published 1-5 papers each, 13 published 6-10 papers each, 9 published 11-20 papers each, 11 published 21-50 papers each, 2 published 51-100 papers each and 1 published 110 papers each during 2000-19.…”