Cell-Free DNA Screening for Single-Gene Disorders

Abstract Importance In pregnancy, cell-free DNA (cfDNA) represents short fragments of placental DNA released into the maternal blood stream through natural cell death. Noninvasive prenatal screening with cfDNA is commonly used in pregnancy to screen for common aneuploidies. This technology continues to evolve, and laboratories now offer cfDNA screening for single-gene disorders. Objective This article aims to review cfDNA screening for single-gene disorders including the technology, current syndromes for which screening may be offered, limitations, and current recommendations. Evidence Acquisition Original research articles, review articles, laboratory white papers, and society guidelines were reviewed. Results Cell-free DNA screening for single-gene disorders is not currently recommended by medical societies. There may be a role in specific circumstances and only after comprehensive pretest counseling. It can be considered in the setting of some fetal ultrasound anomalies, and usually only after diagnostic testing is offered and declined. Conclusions Given the limitations of using cfDNA screening for single-gene disorders, caution is recommended when considering these tests. It should only be offered with involvement of a reproductive genetic counselor, medical geneticist, or maternal fetal medicine specialist to ensure comprehensive counseling and appropriate utilization. Target Audience Obstetricians and gynecologists, family medicine physicians Learning Objectives After completing this reading, learners should be able to describe how laboratories have expanded cfDNA screening beyond common aneuploidy screening; explain the differences between disorders caused by aneuploidy, copy number variants, and single-gene changes; identify patient populations that may be at increased risk for single-gene disorders and the limitations of cfDNA screening for the disorders; and discuss when to refer a patient to a genetic counselor or maternal fetal medicine specialist if a patient requests cfDNA screening for a single-gene disorder.