The genetic landscape of congenital heart disease in pediatrics: From molecular insights to emerging therapies

Aim: This review aims to explore the genetic basis of congenital heart disease (CHD) in pediatric populations by identifying key gene mutations involved in cardiac development and evaluating the current status of genetic screening and emerging gene-targeted therapies. The objective is to bridge the gap between molecular discoveries and clinical applications in pediatric cardiology. Methodology: A comprehensive literature review was conducted across multiple databases including PubMed, Cochrane Library, Scopus, and ClinicalTrials.gov. Articles published between 2010 and 2024 were selected based on strict inclusion criteria, focusing on pediatric patients with CHD, documented genetic mutations, and studies involving genetic diagnostics or interventions. Data were extracted regarding gene function, mutation effects, intervention types (e.g., genetic screening, CRISPR-Cas9 therapy), and clinical outcomes. Results: Key genetic mutations such as NKX2-5, GATA4, TBX5, NOTCH1, and CHD7 were identified as major contributors to various forms of CHD, including atrial and ventricular septal defects, valve anomalies, and syndromic heart conditions. These mutations affect transcriptional networks critical for cardiac morphogenesis. Genetic screening has proven valuable in early diagnosis and family counseling, while preclinical studies using CRISPR-Cas9 and other gene-editing technologies show promise in correcting pathogenic mutations. However, gene therapy remains largely experimental and is not yet applied in routine clinical practice. Conclusion: Genetics plays a central role in the etiology and progression of congenital heart disease in children. The integration of genetic testing into pediatric cardiology is transforming diagnostic and management approaches. Although gene-targeted therapies are still in developmental stages, ongoing research supports their potential as future curative interventions. Large-scale clinical trials and ethical considerations will be essential for translating these innovations into standard care.