Enhancing Prenatal Genetic Evaluation Through the Combination of Single-Gene Non-Invasive Prenatal Screening and...

Cell free DNA (cfDNA) screening for common aneuploidies is now widely integrated into prenatal care, and recent advances in next-generation sequencing, enhanced by unique molecular indexing methodology, have enabled cfDNA for selected single-gene disorders (cfDNA-SGD). Commercially available cfDNA-SGD panels target predominantly either de novo autosomal dominant or X-linked conditions that have recognizable prenatal or neonatal phenotypes. However, it remains a screening modality that relies on placental cell-free DNA, and encounters limitations. In this review, we summarize a currently available cfDNA-SGD panel that screens for 25 autosomal or X-linked dominant conditions corresponding to 30 unique genes, with several genes contributing to multiple conditions on the panel. We highlight the potentially associated prenatal and postnatal phenotypes and the imaging modalities that may help refine a prenatal genetic evaluation. We also discuss how ultrasound, fetal echocardiography, and fetal MRI across all trimesters can refine the prenatal differential diagnosis and help contextualize cfDNA-SGD results, while emphasizing that imaging findings remain the primary guide for management and that confirmatory diagnostic testing is required before clinical decisions and action.