Unexplained False Negative Results in Noninvasive Prenatal Testing: Two Cases Involving Trisomies 13 and 18. (7th June 2015)

• Record Type: Journal Article
• Authors: Hochstenbach, R.; Page-Christiaens, G. C. M. L.; van Oppen, A. C. C.; Lichtenbelt, K. D.; van Harssel, J. J. T.; Brouwer, T.; Manten, G. T. R.; van Zon, P.; Elferink, M.; Kusters, K.; Akkermans, O.; Ploos van Amstel, J. K.; Schuring-Blom, G. H.
• Other Names: Cotter Philip D. Academic Editor.
• Is Part Of: Case reports in genetics. Volume 2015(2015)
• Publication Date: 2015-06-07
• Subjects: Genetics -- Periodicals; Genetics -- Case studies -- Periodicals; Genetics; Genetic Phenomena; Genetics; Periodicals; Case studies; Periodicals; Case Reports; Fulltext; Internet Resources; Periodicals; 576.5
• DOI: 10.1155/2015/926545
• Languages: English
• ISSNs: 2090-6544

Abstract

Abstract : Noninvasive prenatal testing (NIPT) validation studies show high sensitivity and specificity for detection of trisomies 13, 18, and 21. False negative cases have rarely been reported. We describe a false negative case of trisomy 13 and another of trisomy 18 in which NIPT was commercially marketed directly to the clinician. Both cases came to our attention because a fetal anatomy scan at 20 weeks of gestation revealed multiple anomalies. Karyotyping of cultured amniocytes showed nonmosaic trisomies 13 and 18, respectively. Cytogenetic investigation of cytotrophoblast cells from multiple placental biopsies showed a low proportion of nontrisomic cells in each case, but this was considered too small for explaining the false negative NIPT result. The discordant results also could not be explained by early gestational age, elevated maternal weight, a vanishing twin, or suboptimal storage or transport of samples. The root cause of the discrepancies could, therefore, not be identified. The couples involved experienced difficulties in accepting the unexpected and late-adverse outcome of their pregnancy. We recommend that all parties involved in caring for couples who choose NIPT should collaborate to clarify false negative results in order to unravel possible biological causes and to improve the process of patient care from initial counseling to communication of the result.