OBJECTIVETo assess the value of genome-wide high-resolution chromosomal microarray analysis (CMA) for the delineation of pathogenesis for fetal ventriculomegaly diagnosed by ultrasound or magnetic resonance imaging (MRI).

METHODSThree hundred and forty-one cases of fetal ventriculomegaly were collected. The samples were grouped based on the extent of lateral ventricular dilatation, presence of additional features, site of occurrence, and the maternal age. All samples were subjected to karyotyping analysis. For those with a normal karyotype, DNA was extracted and hybridized with an Affymetrix CytoScan HD array. All cases were followed up.

RESULTSAmong the 341 fetuses, 21 (6.2%) were detected with an abnormal karyotype. For the 320 cases with a normal karyotype, 179 (55.9%) have accepted CMA analysis. Potentially pathogenic CNVs were identified in 12 (6.7%) of the 179 cases, whose sizes ranged from 198 kb to 8.71 Mb. These included a 1q21.3q23.1 deletion, a 2q37.3 deletion, a 3p14.1p13 deletion, a 6q25.3 deletion, a 8q11.23 duplication, a 10q21.1 deletion, a 15q11.2 deletion and a 16p13.11p12.3 duplication, a 22q13.33 duplication, a 22q11.21 duplication and a Xp21.1 duplication (Duchenne muscular dystrophy). Pathogenic CNVs were detected respectively in 7.5% and 3.1% of those with mild and severe ventriculomegaly (P=0.615), in 6.1% and 7.4% of those with isolated and non-isolated ventriculomegaly (P=0.732), in 5.6% and 7.9% of those with unilateral and bilateral ventriculomegaly (P=0.511), and in 6.7% of both elderly and non-elderly groups (P=1.000).

CONCLUSIONThe detection rate for abnormal karyotypes among fetuses with ventriculomegaly was 6.2%. CMA can increase the detection rate by approximately 6.7%. There was no significant correlation between ventriculomegaly and presence of pathogenic CNVs. In clinical practice, fetuses with ventriculomegaly and a normal karyotype should be considered for CMA analysis.