False negative non-invasive prenatal screening result for trisomy 18: a case report

Abstract

We hereby reported a case of false negative non-invasive prenatal screening (NIPS) for trisomy 18. The fetus with increased nuchal translucency (3.2 mm) detected by ultrasound scan at 13+4 gestational weeks received NIPS and the result was negative in chromosomes 21, 18 and 13. A routine ultrasound examination at 22 weeks of gestation revealed multiple anomalies and a second NIPS was offered, which showed a negative result again. The pregnancy was terminated at 22+3 weeks. Multiple fetal and placental biopsies were collected for chromosome analysis using copy number variation sequencing based on high-throughput sequencing and fluorescence in situ hybridization. The fetal karyotype was shown to be 47,XY,+18 in fetal tissues (skin and liver) and umbilical cord, while no chromosomal abnormalities was detected at or near the center of the fetal and maternal surface of the placenta. Results of the chromosomal analysis along the edges of the fetal and maternal surfaces of the placenta were Chr18:47,XY,+18[60]/46,XY[40] and Chr18:47,XY,+18[35]/46,XY[65], respectively. We inferred that placental mosaicism was the cause of the false negative NIPS result. Therefore, genetic counseling before and after NIPS is necessary. Follow-up ultrasound is important for NIPS-negative patients. Invasive prenatal diagnosis is recommended when abnormal ultrasound markers with possible genetic etiology were recognized. Key words: Trisomy 18 syndrome; Ultrasonography, prenatal; False negative reactions; Nuchal translucency measurement