Prenatal Screening for Microdeletions and Rare Autosomal Aneuploidies

Abstract

Noninvasive prenatal screening with cell-free DNA is now considered a first-line screening for common aneuploidies. Advancements in existing laboratory techniques now allow to interrogate the entirety of the fetal genome, and many commercial laboratories have expanded their screening panels to include screening for rare autosomal aneuploidies and copy number variants. Here, we review the currently available data on the performance of fetal cell-free DNA to detect rare autosomal aneuploidies and copy number variants that are associated with clinically significant microdeletion and microduplication syndromes and the current position of medical societies on routine screening for these syndromes.

High positive predictive value 22q11.2 microdeletion screening by prenatal cell‐free DNA testing that incorporates fetal fraction amplification

“…High-risk indications included abnormal ultrasound, abnormal maternal serum screen, chromosome abnormality suspected in fetus, previous pregnancy/child affected with chromosome abnormality, family history, and supervision of other high-risk pregnancy. Average-risk indications included supervision of normal-risk pregnancies, advanced maternal age (which is not considered a risk factor for 22q11.2DS), 3,4 and those that did not specify an indication.…”

“…16 Early diagnosis of 22q11.2DS is associated with improved outcomes for affected individuals. 2,4,18,24,25 Accordingly, the American College of Medical Genetics and Genomics (ACMG) recently recommended that 22q11.2 microdeletion screening by prenatal cfDNA should be offered to all patients. 26 The imperative to provide patients with accurate information about 22q11.2DS risk necessitates a prenatal cfDNA screening assay with excellent performance, as the small size of 22q11.2 deletions makes accurate detection technically challenging.…”