Genetic analysis of fetal corpus callosum abnormalities: a retrospective single-center cohort study

Corpus callosum abnormalities (CCA) is an anomaly that can occur in fetuses during pregnancy. This retrospective cohort study included 86 fetuses with prenatally diagnosed CCA. All cases underwent chromosomal microarray analysis (CMA), with exome sequencing (ES) performed either concurrently (n = 73) or sequentially (n = 3). CMA identified 2 aneuploidies and 10 pathogenic or likely pathogenic copy number variants (P/LP CNVs), yielding a diagnostic rate of 13.9% (12/86) . Among the CMA-negative cases, ES data were available for 90.5% (67/74) of cases and provided an additional diagnostic yield of 26.9% (18/67). The detection rate of pathogenic or likely pathogenic (P/LP) variants was higher in non-isolated CCA cases, especially within the subgroup with multi-system anomalies (53.8%), although this difference did not reach statistical significance. The pregnancy termination rate was significantly higher in cases of non-isolated CCA compared to isolated CCA (79.4% vs. 52.2%, p = 0.013). Termination occurred in all cases with positive CMA results and in 94.4% of cases with positive ES findings. The present study demonstrates that the integration of CMA and ES enhances the diagnostic yield for fetal CCA. Implementing concurrent CMA and ES testing in cases of non-isolated CCA, particularly those involving multi-system anomalies, is recommended to maximize diagnostic efficiency and support timely prenatal decision-making.