Ryan Longman, MD
Prenatal ultrasound detects structural fetal abnormalities in about 3% of pregnancies. When structural fetal abnormalities are found on prenatal ultrasound, diagnostic genetic testing with either CVS or amniocentesis are recommended. Classically, this has meant fetal karyotype and chromosomal microarray testing (CMA). Recently, a new type of genetic testing has become available on fetal samples, whole-exome sequencing (WES). Smogavec et al. assesses this new technology and its ability to detect fetal genetic abnormalities. They retrospectively studied 90 fetuses with abnormalities detected on prenatal ultrasound that had normal CMA results and negative fluorescence in situ hybridization analysis testing for aneuploidy. They found WES testing added a 34.4% increased rate of detection of fetal genetic abnormalities. WES is a powerful tool for genetic diagnosis in fetuses with structural anomalies and should be considered anytime a karyotype or CMA is normal in a fetus with structural anomalies.
Lastly, prenatal genetic diagnosis at an early gestational age is critical for medical management of fetuses with anomalies. In a cohort study, Chen et al . assess the simultaneous combined use of CNV-seq and WES on testing turnaround time. They found by running the testing simultaneously, rather than sequentially, this would decrease testing time from over a month to less than 2 weeks. This strategy of testing could potentially decrease the time from detection of a fetal anomaly on ultrasound to a genetic diagnosis allowing for earlier counseling and medical guidance.