Wick, Myra

AbstractRecently, practices have begun integrating cell‐free DNA‐based noninvasive prenatal screening as a screening option for a variety of genetic conditions. According to the National Society of Genetic Counselors, the integration of cfDNA screening into clinical prenatal practice may “significantly shift the paradigm of prenatal testing and screening for all women.” The purpose of this study was to determine whether group information sessions can feasibly serve as an alternative to extended one‐on‐one genetic counseling for the increasing number of women making decisions about prenatal testing and screening. This study assessed the effect of group genetic information sessions coupled with abbreviated counseling on pregnant women's knowledge about and attitudes toward prenatal testing and screening.

Key Clinical MessageA de novo GFAP variant, p.R376W, was identified in a child presenting with hypotonia, developmental delay, and abnormal brain MRI. Following the 2015 ACMG variant classification guidelines and the functional studies showing protein aggregate formation in vitro, p.R376W should be classified as a pathogenic variant, causative for Alexander disease.

Background.Noninvasive prenatal screening (NIPS) is revolutionizing prenatal screening as a result of its increased sensitivity, specificity. NIPS analyzes cell-free fetal DNA (cffDNA) circulating in maternal plasma to detect fetal chromosome abnormalities. However, cffDNA originates from apoptotic placental trophoblast; therefore cffDNA is not always representative of the fetus. Although the published data for NIPS testing states that the current technique ensures high sensitivity and specificity for aneuploidy detection, false positives are possible due to isolated placental mosaicism, vanishing twin or cotwin demise, and maternal chromosome abnormalities or malignancy.Results.We report a case of false negative cell-free DNA (cfDNA) screening due to fetoplacental mosaicism. An infant male with negative cfDNA screening result was born with multiple congenital abnormalities. Postnatal chromosome and FISH studies on a blood specimen revealed trisomy 13 in 20/20 metaphases and 100% interphase nuclei, respectively. FISH analysis on tissues collected after delivery revealed extraembryonic mosaicism.Conclusions.Extraembryonic tissue mosaicism is likely responsible for the false negative cfDNA screening result. This case illustrates that a negative result does not rule out the possibility of a fetus affected with a trisomy, as cffDNA is derived from the placenta and therefore may not accurately represent the fetal genetic information.