A Retrospective Review of Copy Number Variants and Ultrasound-Detected Soft Markers

Abstract

Objective: To examine the association of copy number variants (CNV) among fetuses with ultrasound-detected soft markers (USM). Methods: This IRB-approved retrospective cohort study of fetuses with prenatal or children with postnatal chromosomal microarray analysis (CMA) sought to examine an association between clinically relevant CNV (classified as pathogenic CNV or variants of uncertain significance (VUS)) and USM in women w ho delivered at Geisinger between January 2010 and July 2018. The following USM were evaluated: choroid plexus cyst, thickened nuchal fold, absent or hypoplastic nasal bone, echogenic intracardiac focus, echogenic bowel, short long bones, and urinary tract dilation. Fetuses or children with known aneuploidy or a single gene disorder were excluded. Odds ratios (OR) of the association between CNV and USM were reported along with associated 95% confidence intervals (CI) and p-values. P values <0.05 were considered significant. Results: Of the 348 fetuses/children, 89 (25.6%) had a clinically relevant CNV. Similar percentages of demographic, delivery and neonate characteristics were noted for those with a clinically relevant CNV and those with a normal microarray analysis. No statistically significant differences were noted am ong those fetuses/children with a clinically relevant CNV and structural anomaly (p = 0.52; OR 1.18, 95% CI 0.72-1.92), presence of one USM (p = 0.72; OR 1.52, 95% CI 0.79-2.92), or presence of more than one USM (p = 0.79; OR 1.56, 95% CI 0.28-8.72). Conclusion: Our data supports a lack of association between a clinically relevant copy number variant and an ultrasound-detected soft marker. A small statistically insignificant increase in odds of a clinically relevant CNV was noted for those fetuses/children with one or more USM.

Clinical Utility of SNP Array Analysis in Prenatal Diagnosis: A Cohort Study of 5000 Pregnancies

“…c 147 cases of structural rearrangement including balanced structural rearrangement, chromosomal heteromorphisms and marker chromosomes were not detected by SNP-array, while SNP-array additionally detected 1 case of mosaic trisomy 22 and 10 cases of microduplication/microdeletion. of clinically significant submicroscopic CNVs in fetuses with abnormality of a single ultrasonic soft marker and multiple ultrasonic soft markers (2.2% vs. 4.2%, chi-squared test, P = 0.55) (Angras et al, 2020).…”

The genetic landscape of copy number variation in a Vietnamese cohort of 5008 fetuses with clinical anomalies during pregnancy

“…Recently, to maximize diagnostic accuracy, CNV analysis has been applied to identify and con rm chromosomal abnormalities among fetuses with sonography-detected soft markers and fetal structural anomalies 15,16 . Many ultrasound soft markers such as echogenic intracardiac focus, echogenic bowel, fetal ventriculomegaly, hypoplastic/aplastic nasal bone, and nuchal translucency have been investigated for their relationships with abnormal CNVs [17][18][19][20][21][22][23][24][25] . Multiple congenital structural anomalies have been studied for their correlations with CNVs in early prenatal diagnosis [26][27][28][29][30][31][32][33][34][35][36][37] .…”