Confined Placental Trisomy 18 Mosaicism Detected by Maternal Serum and Prenatal cfDNA Screening [21M

Abstract

INTRODUCTION: We describe a case in which maternal serum screening (MSS) and prenatal cell-free DNA (cfDNA) screening were consistent with trisomy 18, later confirmed as confined placental mosaicism (CPM) of trisomy 18. The correlation between MSS and prenatal cfDNA screening, the common relationship of the techniques to placental function, and implications for clinical management are discussed. METHODS: A specimen for prenatal cfDNA screening was submitted to our laboratory with an indication of a 1:22 risk for trisomy 18 on first-trimester MSS. Prenatal cfDNA screening using massively parallel shotgun sequencing was performed and outcome information was obtained by laboratory genetic counselors. RESULTS: Prenatal cfDNA screening was positive for trisomy 18 in a male fetus; fetal fraction was 6.4% and the Z-score for chromosome 18 was 16. Amniocentesis was consistent with a normal male fetus on routine cytogenetic and microarray analyses. No anomalies were visualized on ultrasound. Delivery was significant for preterm labor, and the neonatal course was unremarkable. Microarray performed on placental tissue revealed mosaic trisomy 18, consistent with CPM. CONCLUSION: CPM identification has clinical management implications, such as the associated risk for intrauterine growth restriction (IUGR). The results of MSS and prenatal cfDNA screening in this case were consistent with trisomy 18, but were later revealed to represent CPM. It is well-established that analytes used in MSS are produced by the placenta, and that the cfDNA analyzed in prenatal screening is of feto-placental origin. This case contributes to the understanding of CPM, MSS analytes, feto-placental cfDNA, for improved clinical management.