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.