The Incremental Yield of CMA over Karyotype in Isolated Absent/Hypoplastic Nasal Bone-A Systematic Review and...

Background/Objectives: Absent or hypoplastic nasal bone is strongly associated with Trisomy 21 and other common aneuploidies. Nevertheless, there is a growing body of literature that has associated absence or hypoplasia of the nasal bone with underlying genetic aberrations, other than Trisomy 21. While karyotyping effectively identifies substantial structural mutations, it is limited by its inability to detect submicroscopic copy number variants, thereby constraining the identification of pathological submicroscopic DNA gains or losses. The main objective of our study was to conduct a systematic literature review and a meta-analysis to evaluate the incremental yield of chromosomal microarray analysis compared to karyotyping in cases of isolated absence/hypoplasia of the fetal nasal bone. Methods: Our review was designed according to the PRISMA guidelines. It included all observational studies that reported the results of CMA testing in fetuses diagnosed with absent or hypoplastic nasal bone without additional structural abnormalities or findings that would not qualify as structural abnormalities (soft signs) (isolated absent/hypoplastic nasal bone). Results: The study included 15 studies with a total of 1328 cases of affected fetuses that met the inclusion criteria for analysis. Combined data from these studies revealed an overall 3% incremental yield of CMA over karyotyping (95% CI 1-4%, I² = 62%) in isolated cases. Conclusions: Our findings may be beneficial in clinical practice to provide management strategies and counsel couples, personalizing, as such, patient care and assisting clinicians when encountering this prevalent clinical entity.