Confined placental mosaicism for 22q11.2 deletion as the etiology for discordant positive NIPT results

Abstract

22q11.2 deletion, the most common microdeletion syndrome within the general population, is estimated to have a prevalence of 1 in 3000 to 6000. Non-invasive prenatal testing has recently expanded to include screening for several microdeletions including 22q11.2. Given the expansion of prenatal screening options to include microdeletions, it is important to understand the limits of this technology and the variety of reasons that a discordant positive result can occur. Here, we describe a case of a pregnant woman who received a positive non-invasive prenatal maternal plasma screen for 22q11.2 deletion. Maternal and postnatal neonatal peripheral blood cytogenetic, PCR, and fluorescence in situ hybridization studies were normal, but the placenta was mosaic for 22q11.2 deletion in two of three biopsy sites. This case illustrates both the complexities of pre- and post-test counseling for microdeletion screening and the potential for a discordant positive microdeletion result because of confined placental mosaicism. © 2017 John Wiley & Sons, Ltd.

Prognosis for pregnancies with trisomy 16 confined to the placenta: A Danish cohort study

“…Using cell‐free placental DNA in maternal blood, which is suspected to originate from placental trophoblast cells, to estimate the risk of aneuploidy in the fetus itself has introduced new challenges in the interpretation of this prenatal screening test. Results of analysis of cell‐free placental DNA may be comparable with those from chromosome analysis after short term culture, which could explain some of the false positive results . Also, when offering noninvasive techniques without prior cFTS, it is possible that even a very low frequency of trisomic cells will be disclosed in some placentas, thereby identifying chromosomal mosaicism that would not have been identified using the previous techniques.…”

Chromosomal microarray analysis on uncultured chorionic villus sampling can be complicated by confined placental mosaicism for aneuploidy and microdeletions

“…In another case, an exonic deletion of the STS gene on Xp22.31 was reported to be CPM type I . In a third case, a mosaic 22q11.2 deletion was detected through NIPS, which was subsequently found to be present in two out of three placental biopsy sites, while absent from maternal and postnatal neonatal peripheral blood samples …”

Congenital heart diseases and cardiovascular abnormalities in 22q11.2 deletion syndrome: From well‐established knowledge to new frontiers

“…Further technological advances are likely to improve its accuracy. NIPT may identify previously undiagnosed mothers as well as it may lead to a discordant positive result (e.g., due to mosaicism) (Bunnell, Zhang, Lee, Bianchi, & Wilkins-Haug, 2017). Thus, a thorough pre- and post-NIPT counseling is essential.…”