Prenatal diagnosis of submicroscopic chromosomal aberrations in fetuses with ventricular septal defects by chromosomal microarray-based analysis

Objectives To evaluate the usefulness of chromosomal microarray analysis in fetuses with ventricular septal defects (VSDs) with or without associated anomalies and normal karyotype. Methods Fetuses with VSDs and normal karyotypes were investigated by using an Affymetrix CytoScan HD array. The cases were classified as isolated or nonisolated VSDs. Results Among the 52 VSD fetuses, 22 (42.3%) had isolated defects and 30 (57.7%) had additional other ultrasound anomalies. Twenty‐six CNVs were identified in 18 fetuses (34.6%), 15 benign CNVs were detected in 11 (21.2%) fetuses, and 8 pathogenic CNVs were detected in 6 (11.5%) fetuses. After excluding 2 fetuses with 22q11.2 deletion syndrome, the rate of pathogenic CNVs was 7.7%. The proportion of variants of unknown significance was 5.8% (3/52). In five cases, additional malformations were detected after birth or abortion, and one case had a prenatal isolated VSD. The detection rate of pathogenic CNVs in nonisolated VSDs was nonsignificantly higher than that in prenatal or postnatal isolated VSDs (4.5%, 1/22 vs 16.7%, 5/30, P = 0.226; 0/21 vs 19.4%, 6/31, P = 0.07). Conclusions The results demonstrated the value of chromosomal microarray analysis in the prenatal diagnosis of VSDs. The complexity of other defects enhanced the frequency of pathogenic CNVs, although the results were not significantly different. © 2016 John Wiley & Sons, Ltd. What's Already Known About This Topic? Ventricular septal defects are the most common form of congenital cardiovascular anomaly; approximately 20 to 40% of ventricular septal defects are attributable to Mendelian diseases or chromosomal aneuploidies, while the remaining are attributable to non‐Mendelian causes that are poorly understood. Chromosomal microarray analysis has been successfully applied to identify copy number variations in postnatal and prenatal subjects with congenital heart disease and has enabled whole‐genome screening for chromosomal imbalances at higher resolution than conventional karyotyping. Subgroup analyses of different types of congenital heart disease and associated copy number variation are rare. What Does This Study Add? In this study, our data show that chromosomal microarray analysis is a valuable tool for identifying unbalanced submicroscopic chromosome abnormalities in the prenatal diagnosis of ventricular septal defects (VSDs). The detection rate of copy number variations in VSDs with other ultrasound anomalies was nonsignificantly higher than t