Pitfalls of prenatal diagnosis associated with mosaicism

Abstract

Key content Fetal placental mosaicism, of which confined placental mosaicism is a subtype, occurs in 2–3% of pregnancies. Confined placental mosaicism may lead to a false positive result on non‐invasive prenatal testing (NIPT) for common aneuploidies. The risk of mosaicism in a chorionic villus sample (CVS) following a positive NIPT result is 2, 4, 22 and 59% for trisomy 21, 18, 13 and 45, X respectively. Following a positive NIPT result in the absence of a significant fetal structural anomaly (FSA), care is required in selecting the optimal diagnostic invasive test. Discussion of the limitations and implications is essential and referral to clinical genetics may be warranted. Learning objectives To understand the embryological causes for and types of fetal placental mosaicism. To appreciate underlying principles in NIPT and genomic testing strategies in relation to mosaicism. To follow suggested clinical management principles in relation to prenatal test counselling. Ethical issues Clinicians face a dilemma following a high‐risk NIPT result in the setting of normal ultrasound. Awaiting long‐term culture, as opposed to short‐term culture on CVS, or amniocentesis delays potential termination of pregnancy. Sex chromosome abnormalities on NIPT without an identifiable FSA cannot be interpreted reliably. Hence, NIPT should not be offered for sex chromosome aneuploidy.