Non-invasive prenatal testing for sex chromosome abnormalities: a source of confusion

Cell-free fetal DNA has received significant attention for the purposes of prenatal genetic testing in the past decade. Fetal DNA testing is a new method and promising for many applications such as aneuploidy screening, prenatal diagnosis, prediction of preeclampsia and more. A 37-year-old primigravida, with a pregnancy conceived by intracytoplasmic sperm injection (ICSI), was offered non-invasive prenatal testing (NIPT) due to advanced maternal age. NIPT performed at 23 weeks' gestation reported a diagnosis of monosomy X. She was offered an amniocentesis, which revealed a euploid fetus with no sex chromosome abnormalities. Even with single nucleotide polymorphism-based NIPT, positive predictive value for detection of sex chromosome abnormalities is around 50%. Positive results of NIPT should be heeded with caution and an invasive diagnostic procedure should be performed, especially for rare chromosomal abnormalities and sex chromosome abnormalities where NIPT performs subpar compared to its performance for detection of trisomy 21.