Exome Sequencing in the Evaluation of the Fetus With Structural Anomalies

Abstract Prenatal whole exome sequencing (WES) in the fetus with isolated or multiple structural anomalies has increased potential to identify a genetic diagnosis above standard genetic testing methods. Fetal DNA extracted from chorionic villi or amniocytes is currently required, but in time WES will be possible on cell-free DNA in maternal blood. Prenatal WES can increase understanding of the genetic etiology of congenital malformation and enable individualized pregnancy management. WES and whole genome sequencing are increasingly being used to investigate perinatal loss and enable genomic-informed treatment in critically ill newborns with undiagnosed genetic disease. Prenatal WES presents additional technical, ethical, and resource-related challenges, and professional guidance alongside patient views and discussions on ethics are emerging. This chapter summarizes the evidence for WES in the fetus with ultrasound evident congenital anomalies, as well as the available literature on patient and provider views, ethical implications, and the development of sequencing applications in the perinatal and neonatal context, alongside the prenatal utility of this developing technology.