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Understanding the Genetic and Non-Genetic Interconnections in the Aetiology of Syndromic Congenital Heart Disease: An Updated Review: Part 2

  • Congenital Heart Disease (RA Krasuski and G Fleming, Section Editors)
  • Published:
Current Cardiology Reports Aims and scope Submit manuscript

Abstract

Purpose of Review

Approximately 30% of syndromic cases diagnosed with CHD, which lure us to further investigate the molecular and clinical challenges behind syndromic CHD (sCHD). The aetiology of sCHD in a majority of cases remains enigmatic due to involvement of multiple factors, namely genetic, epigenetic and environmental modifiable risk factors for the development of the disease. Here, we aim to update the role of genetic contributors including chromosomal abnormalities, copy number variations (CNVs) and single gene mutations in cardiac specific genes, maternal lifestyle conditions, environmental exposures and epigenetic modifiers in causing CHD in different genetic syndromes.

Recent Findings

The exact aetiology of sCHD is still unknown. With the advancement of next-generation technologies including WGS, WES, transcriptome, proteome and methylome study, numerous novel genes and pathways have been identified. Moreover, our recent knowledge regarding epigenetic and environmental regulation during cardiogenesis is still evolving and may solve some of the mystery behind complex sCHD.

Summary

Here, we focus to understand how the complex combination of genetic, environmental and epigenetic factors interact to interfere with developmental pathways, culminating into cardiac and extracardiac defects in sCHD.

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Data Availability

There are different databases such as American and Denmark databases which keep record for the birth surveillance as well as genetic counselling. However, post natal-care as well as improvement in clinical research may aid in better understanding the etiology of disease. The susceptibility to disease may also decrease.

Abbreviations

ALGS:

Alagille syndrome

AS:

Aortic stenosis

ASD:

Atrial septal defect

AVSD:

Atrioventricular septal defect

BAV:

Bicuspid aortic valve

CdC:

Cri-du-chat syndrome

CNVs:

Copy number variations

CoA:

Coarctation of aorta

DCM:

Dilated cardiomyopathy

DILV:

Double inlet left ventricle

DORV:

Double outlet right ventricle

DS:

Down syndrome

EA:

Ebstein’s anomaly

HCM:

Hypertrophic cardiomyopathy

HLHS:

Hypoplastic left heart syndrome

HOS:

Holt-Oram syndrome

IAA:

Interrupted aortic arch

JS:

Jacobsen syndrome

LVOTO:

Left ventricular outflow tract obstruction

NS:

Noonan syndrome

NGS:

Next-generation sequencing

OFT:

Outflow tract

PAPVR:

Partial anomalous pulmonary venous return

PDA:

Patent ductus arteriosus

PS:

Pulmonary stenosis

PTA:

Persistent truncus arteriosus

SNVs:

Single nucleotide variants

SVAS:

Supravalvular aortic stenosis

TA:

Tricuspid atresia

TAPVR:

Total anomalous pulmonary venous return

TGA:

Transposition of great arteries

ToF:

Tetralogy of Fallot

VSD:

Ventricular septal defect

WS:

Williams syndrome

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Acknowledgements

We are extremely thankful to Prof. Rajiva Raman, Department of Zoology, BHU, Varanasi, India for critically reviewing the manuscript, grammatical corrections and for his valuable suggestions.

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  1. Cytogenetics Laboratory, Department of Zoology, Institute of Science, Banaras Hindu University, Varanasi, 221005, Uttar Pradesh, India

    Jyoti Maddhesiya & Bhagyalaxmi Mohapatra

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JM has performed the literature search and prepared the original draft including all figures and tables. BM sketched the outline for the article, critically supervised and revised the manuscript at every single step. Both authors read and approved the final manuscript.

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Correspondence to Bhagyalaxmi Mohapatra.

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Maddhesiya, J., Mohapatra, B. Understanding the Genetic and Non-Genetic Interconnections in the Aetiology of Syndromic Congenital Heart Disease: An Updated Review: Part 2. Curr Cardiol Rep 26, 167–178 (2024). https://doi.org/10.1007/s11886-024-02020-x

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