Multicenter clinical experience with non‐invasive cell‐free DNA screening for monosomy X and related X‐chromosome variants

Abstract

AbstractObjectiveWe aimed to investigate how the presence of fetal anomalies and different X chromosome variants influences Cell‐free DNA (cfDNA) screening results for monosomy X.MethodsFrom a multicenter retrospective survey on 673 pregnancies with prenatally suspected or confirmed Turner syndrome, we analyzed the subgroup for which prenatal cfDNA screening and karyotype results were available. A cfDNA screening result was defined as true positive (TP) when confirmatory testing showed 45,X or an X‐chromosome variant.ResultsWe had cfDNA results, karyotype, and phenotype data for 55 pregnancies. cfDNA results were high risk for monosomy X in 48/55, of which 23 were TP and 25 were false positive (FP). 32/48 high‐risk cfDNA cases did not show fetal anomalies. Of these, 7 were TP. All were X‐chromosome variants. All 16 fetuses with high‐risk cfDNA result and ultrasound anomalies were TP. Of fetuses with abnormalities, those with 45,X more often had fetal hydrops/cystic hygroma, whereas those with “variant” karyotypes had different anomalies.ConclusionBoth, 45,X or X‐chromosome variants can be detected after a high‐risk cfDNA result for monosomy X. When there are fetal anomalies, the result is more likely a TP. In the absence of fetal anomalies, it is most often an FP or X‐chromosome variant.