Prenatal Whole-Genome Sequencing for Fetal Anomalies: Diagnostic Performance, Challenges, and Clinical Implications

Narrative review of prenatal WGS (1966-2025): simultaneous detection of aneuploidies, CNVs, SNVs, small indels and structural variants; comparison with trio exome + CMA; clinical implementation challenges (turnaround time, cost, VUS, prenatal interpretation)

Exhaustive narrative review of prenatal WGS for fetal anomalies, covering PubMed publications from 1966 to December 2025. Prenatal WGS enables simultaneous detection of aneuploidies, CNVs, SNVs, small indels, structural variants and regions of absence of heterozygosity. Its diagnostic performance exceeds that of the trio exome + CMA combination in the most recent cohorts. The main implementation challenges identified are turnaround time, cost, management of prenatal VUS, and interpretation in a clinical context of irreversible decision-making.

Synthesis written by Geno'X. For the full original abstract, please refer to the source publication.

Prenatal WGS is positioned as a first-line test in leading fetal medicine programs (NHS Genomic Medicine Service). This review informs HAS deliberations in France on the evolution of the prenatal diagnosis pathway. The management of prenatal VUS remains the main barrier to large-scale implementation.

prenatal diagnostic impact +3; exhaustive narrative review of literature (1966-2025) +2; direct clinical relevance (NHS agenda) +2