Rare autosomal trisomies detected by non-invasive prenatal testing: an overview of current knowledge

Abstract

Non-invasive prenatal testing has been introduced for the detection of Trisomy 13, 18, and 21. Using genome-wide screening also other "rare" autosomal trisomies (RATs) can be detected with a frequency about half the frequency of the common trisomies in the large population-based studies. Large prospective studies and clear clinical guidelines are lacking to provide adequate counseling and management to those who are confronted with a RAT as a healthcare professional or patient. In this review we reviewed the current knowledge of the most common RATs. We compiled clinical relevant parameters such as incidence, meiotic or mitotic origin, the risk of fetal (mosaic) aneuploidy, clinical manifestations of fetal mosaicism for a RAT, the effect of confined placental mosaicism on placental function and the risk of uniparental disomy (UPD). Finally, we identified gaps in the knowledge on RATs and highlight areas of future research. This overview may serve as a first guide for prenatal management for each of these RATs.

Fig. 1. Frequency of RATs detected by NIPT.

Frequency of different RATs observed per 100,000 NIPTs in a high risk obstetric population (blue, data from the review by Benn et al., 2019) and the general obstetric population (amber, data from Van der Meij et al., 2019 and Van den Bogaert et al., 2021) [–7].

Fig. 2. Risk of fetal trisomy per RAT detected by NIPT in population-based studies.

Number of cases per RAT detectected by NIPT in population-based studies are presented with in blue the cases without fetal confirmation and in amber the cases with fetal confirmation [6, 7].