Noninvasive prenatal testing creates an opportunity for antenatal treatment of Down syndrome

Trisomy 21 (T21) is the most common autosomal aneuploidy that is associated with intellectual disability. It is the focus of many prenatal screening programs across the globe. Pregnant women who receive a prenatal diagnosis of T21 in their fetus currently have the option of continuing or terminating their pregnancy, but no fetal treatment is available. In this paper, we review compelling morphogenetic, cellular, and molecular studies that, taken together, suggest that there is an important window of opportunity during fetal life to positively impact brain development to improve postnatal neurocognition and behavior. Although substantial progress has been made in understanding the basic neurobiology of Down syndrome (DS), the majority of pre-clinical trials is currently focused on adults. There are a number of challenges in the identification and development of novel antenatal therapies for DS, including the lack of toxicity and teratogenicity for the pregnant woman and the fetus, evidence that the compounds can cross the placenta and achieve therapeutic levels, and the demonstration of clinical improvement. Preliminary experiments in mouse models suggest that prenatal treatment of DS is an achievable goal. © 2013 John Wiley & Sons, Ltd.     

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

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.