Congenital heart defects (CHDs) are most prevalent cardiac defects that occur at birth, leading to significant neonatal mortality and morbidity, especially in the developing nations. Among the CHDs, conotruncal heart defects (CTDs) are particularly noteworthy, comprising a significant portion of congenital cardiac anomalies. While advances in imaging and surgical techniques have improved the diagnosis, prognosis, and management of CTDs, their molecular genetics and genomic substrates remain incompletely understood. This expert review covers the recent advances from January 2016 onward and examines the complexities surrounding the genetic etiologies, prevalence, embryology, diagnosis, and clinical management of CTDs. We also emphasize the known copy number variants and single nucleotide variants associated with CTDs, along with the current planetary health research efforts aimed at CTDs in large cohort studies. In all, this comprehensive narrative review of molecular genetics and genomics research and innovation on CTDs draws from and highlights selected works from around the world and offers new ideas for advances in CTD diagnosis, precision medicine interventions, and accurate assessment of prognosis and recurrence risks.
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