Genetics of Congenital Heart Disease: A Narrative Review of Challenges and Strategies in Identifying Novel Genes.

Congenital heart disease (CHD) is the most common congenital anomaly. While surgical and interventional advancements have improved survival, the management of associated complications and comorbidities remains complex and would benefit from a personalised approach that more accurately predicts individualised risks and prognoses. Recently, next-generation sequencing has uncovered diverse genetic factors, including epigenetic modifications, somatic mosaicism and regulatory non-coding variants. Despite these advances, challenges persist in translating genomic data into clinical risk prediction and therapeutic guidance. Experimental approaches, such as patient-derived induced pluripotent stem cells (iPSCs) and single-cell sequencing, offer promising preclinical models for interpreting novel variants. Integrating genomic insights into clinical practice requires multidisciplinary team collaboration. The clinicians need to keep themselves abreast with current genomic advancements to optimise customised, individualised care to improve future outcomes for patients with CHD. We aim to provide an overview of the advances in genomic technologies linking the genetics of cardiac development with the pathogenesis of CHD for a better understanding of molecular-morphological correlation.