Association between isolated mild symmetrical ventriculomegaly and fetal chromosomal aberrations

Abstract

The identification of mild fetal ventriculomegaly prompts further evaluation focused on determining whether additional structural anomalies, genetic abnormalities or congenital infections are present. The aim of this study is to evaluate the frequency of chromosomal aberrations in fetuses with isolated mild symmetrical ventriculomegaly and determine the risk for a fetus with isolated mild ventriculomegaly to have chromosomal abnormality in a back ground. Additionally, we have performed an evaluation of the chromosomal microarray findings in a series of five fetuses with isolated mild symmetrical ventriculomegaly and a normal karyotype. The retrospective observational study included karyotype evaluation of 102 fetuses with isolated mild symmetrical ventriculomegaly identified at the time of the routine midpregnancy scanning. In five cases array-CGH was performed and the obtained data were compared with the data in the bioinformatics databases. Among fetuses with isolated mild symmetrical ventriculomegaly chromosome aberrations were found in 2 (1,96%) fetuses. In both cases autosomal aneuploidy was detected, and those are trisomy 21 and trisomy 18, respectively. The finding of a mild symmetrical isolated ventriculomegaly on the routine ultrasound fetal exam in the second trimester had low sensitivity, but high specificity and negative predictive value in the prediction of chromosome anomalies. Copy number variants (microduplications/microdeletions) were detected in four cases (80%). A search for the similar variants in NCBI ClinVar, DECIPHER, OMIM and ENSEMBL data bases, revealed that the microdeletions/microduplications detected in four fetuses in our study cannot be related with ventriculomegaly development. Our findings suggest that karyotyping is not justified in fetuses with isolated mild symmetrical ventriculomegaly (10-15 mm), in a low risk population. Therefore, when mild fetal ventriculomegaly is found in a low risk population, additional non-invasive procedures for chromosome aberration screening (such as noninvasive prenatal screening based on cell-free fetal DNA) are recommended, before making the decision to perform invasive diagnostic procedures.