Noninvasive screening by cell-free DNA for 22q11.2 deletion: Benefits, limitations, and challenges

Cell-free DNA (cfDNA) testing for fetal aneuploidy is one of the most important technical advances in prenatal care. Additional chromosome targets beyond common aneuploidies, including the 22q11.2 microdeletion, are now available because of this clinical testing technology. While there are numerous potential benefits, 22q11.2 microdeletion screening using cfDNA testing also presents significant limitations and pitfalls. Practitioners who are offering this test should provide comprehensive pretest and posttest prenatal counselling. The discussion should include the possibility of an absence of a result, as well as the risk of possible discordance between cfDNA screening results and the actual fetal genetic chromosomal constitution. The goal of this review is to provide an overview of the cfDNA testing technologies for 22q11.2 microdeletions screening, describe the current state of test validation and clinical experience, review “no results” and discordant findings based on differing technologies, and discuss management options.