High positive predictive value 22q11.2 microdeletion screening by prenatal cell‐free DNA testing that incorporates fetal fraction amplification

Abstract

AbstractObjective22q11.2 deletion syndrome (DS) is a serious condition with a range of features. The small microdeletion causing 22q11.2DS makes it technically challenging to detect using standard prenatal cfDNA screening. Here, we assess 22q11.2 microdeletion clinical performance by a prenatal cfDNA screen that incorporates fetal fraction (FF) amplification.MethodsThe study cohort consisted of patients who received Prequel (Myriad Genetics, Inc.), a prenatal cfDNA screening that incorporates FF amplification, and met additional eligibility criteria. Pregnancy outcomes were obtained via a routine process for continuous quality improvement. Samples with diagnostic testing results were used to calculate positive predictive value (PPV).Results379,428 patients met study eligibility criteria, 76 of whom were screen‐positive for a de novo 22q11.2 microdeletion. 22 (29.7%) had diagnostic testing results available, and all 22 cases were confirmed as true positives, for a PPV of 100% (95% CI 84.6%–100%). This performance was based on cases that ranged broadly across FF (5.9%–41.1%, mean 23.0%), body mass index (22.3–44.8, mean 29.9), and gestational age at testing (10.0w–34.6w, median 12.7w). Ultrasound findings in screen‐positive pregnancies were consistent with those known to be associated with 22q11.2DS.Conclusion22q11.2 microdeletion screening that incorporates FF amplification demonstrated high PPV across both general and high‐risk population cohorts.