Applications for cell-free DNA testing beyond common aneuploidy

Key content
• Cell-free fetal DNA (cffDNA) screening test performance for sex chromosome aneuploidies
(SCAs), copy number variants (CNVs), rare autosomal trisomies (RATs) and single gene disorders
• cffDNA screening for detection of pre-eclampsia and malignancy
• Investigation of recurrent miscarriage using cffDNA
• Alternative approaches to interrogating free fetal DNA

Learning Objectives
• Appreciate there is a lack of robust evidence regarding cffDNA screening test performance for
expanded applications.
• Some but not all countries endorse SCA screening and screening for some CNVs such as
22q.11.2 microdeletion syndrome
• Expanded applications of cffDNA screening pose interpretational and ethical challenges
• The diagnostic confirmatory test of choice following a high-chance screening result for the
aforementioned conditions is an amniocentesis

Ethical Issues
• Indirect sex determination may occur with SCA screening
• Expanded applications for cffDNA screening in the UK fall outside recommendations (often provided in the private sector)

Keywords
• Cell-free fetal DNA
• Non-invasive prenatal testing
• Sex chromosome aneuploidy
• Rare autosomal trisomy
• Copy number variant