Clinical Application of Genetic Testing for Fetal Agenesis of the Corpus Callosum in Prenatal Diagnosis

BACKGROUND: This study aimed to investigate the clinical application of genetic testing in the prenatal diagnosis of fetal agenesis of the corpus callosum (ACC). METHODS: Fetuses with ACC confirmed by prenatal systematic ultrasound and fetal MRI imaging underwent invasive prenatal diagnostic procedures. Amniotic fluid samples from the fetuses were collected for karyotype analysis and/or chromosomal microarray analysis (CMA). For ACC fetuses with normal karyotype and/or CMA results, whole-exome sequencing (WES) was further performed. RESULTS: Among the 15 ACC fetuses, karyotype analysis was performed in 14 cases, with one case (7.14%, 1/14) showing an abnormal chromosomal karyotype. CMA was performed in 14 cases, with pathogenic or likely pathogenic copy number variations (CNVs) detected in 4 cases (28.57%, 4/14), including microdeletions at 13q32.2q34, 18q21.2q21.31, 16p13.3, and 16p12.2. Among the 8 ACC fetuses with normal karyotype analysis and/or CMA re-sults, WES was further performed on both the fetuses and their parents, revealing two likely pathogenic variants in two cases (25%, 2/8) involving the FOXG1 and B3GALNT2 genes. CONCLUSIONS: Prenatal genetic diagnosis is of significant importance for ACC fetuses. CMA demonstrates a higher detection rate than karyotyping. WES can provide additional genetic diagnostic insights for ACC fetuses with normal karyotype and/or CMA.