Uncovering the Genetic Landscape of Spinal Dysraphism: A Retrospective Analysis of 150 Fetal Cases

Abstract

Objective: Spinal dysraphism (SD) results from incomplete neural tube closure and encompasses a heterogeneous group of congenital anomalies with genetic and environmental etiologies. Although genetic contributions are recognized, causative variants remain insufficiently defined, and the clinical implications of extended genetic testing on parental decision-making are not well characterized. This study evaluated the diagnostic utility of extended genetic testing, including exome sequencing (ES), in fetuses with prenatally diagnosed SD and its influence on clinical management. Methods: We retrospectively analyzed 150 pregnancies with a prenatal diagnosis of SD referred to our center between July 2021 and May 2025. All cases underwent detailed phenotyping, genetic counseling, and were offered extended genetic testing, including karyotyping, chromosomal microarray (CMA), and trio-based ES. Results: Genetic testing, including karyotyping (110/110), CMA (61, 55.5%), and ES (66, 60.0%), was performed in 110 fetuses. Genetic anomalies were detected in 19 fetuses (17.3%). ES revealed or confirmed 16 pathogenic, likely pathogenic, or uncertain variants in 14/66 (21.21%) fetuses, including one with three distinct variants. Notably, twelve of these fetuses would not have been identified without ES. Although no definitive causative molecular variants were detected, ES results influenced the parental decision to terminate the pregnancy in four cases. Conclusion: ES increases diagnostic yield in SD and may influence prenatal decision-making.