OBJECTIVE: Monogenic disorders (MDs), often associated with developmental delay, intellectual disability, hypotonia, or dysmorphic facial features, typically go undetected during pregnancy. These disorders are frequently caused by de novo single nucleotide variants (SNVs), which are not currently covered by routine non-invasive prenatal testing (NIPT). This screening gap limits informed decision-making in pregnancy and can lead to the unexpected birth of neonates with severe conditions. The aim of this study was to look for evidence of whether de novo SNVs can be detected through NIPT and to assess the possibility of screening for autosomal dominant MDs in cell-free DNA in maternal plasma. METHODS: A systematic literature review conducted on the 27th of February 2024 identified 12 studies examining NIPT of multiple genes associated with MDs. An additional citation analysis for the four most recent studies that were included in the systematic review was conducted on 10th of April 2025. Four additional studies met our inclusion criteria and were incorporated in the final analysis. RESULTS: The studies demonstrated that next-generation sequencing of a gene panel or whole exome could detect pathogenic single nucleotide variants in fetuses with high positive predictive values 98.9% (66.7%-100%). CONCLUSION: This review confirms that performing NIPT for de novo and paternally inherited pathogenic variants associated with MDs is technically possible. Ethical considerations, including disorder selection, variant disclosure, and the need for large-scale implementation studies must be addressed to assess the potential risks and ensure effective and responsible implementation.