Subtype-specific distribution of genetic disorders in congenital heart disease: a registry based study from China

Abstract Background Congenital heart disease (CHD) is the leading cause of birth defects. This study aimed to characterize the spectrum of genetic disorders associated with CHD. Methods CHD cases obtained from a provincial birth defect surveillance system in China between 2022 and 2024 were analysed. The frequency and proportion of chromosomal and single-gene disorders across different CHD subtypes were calculated. Results A total of 20,612 births were diagnosed with CHD, with an incidence of 17.15 per 1000 births. Among those with CHD, 1662 (8.06%) underwent genetic testing, and 421 (25.33%) had positive findings. Copy number variants (CNVs) accounted for 58.19% of the cases with positive findings, followed by trisomies. The 22q11.2 region variants were the predominant CNVs, whereas Noonan syndrome-related variants were the leading single-gene defects. Stratified by CHD subtypes, CNVs accounted for more than 70% of the positive genetic findings in cases with tetralogy of Fallot (TOF) and interrupted aortic arch (IAA), whereas single-gene variants were greater than 20% in cases with ventricular septal defect (VSD) and persistent left superior vena cava (PLSVC). The incidence of genetic positive cases was higher in births with Critical CHD and CHD with extracardiac anomalies than in others. Conclusions Genetic abnormalities differed greatly among births with different CHD subtypes. Our findings underscore the importance of genetic tests, even in births with isolated CHD cases.