Case Report: Prenatal imaging and genetic integrated diagnosis of SCN2A encephalopathy—a case of cryptical cortical dysplasia caused by a loss-of-function frameshift genetic variant

Objective SCN2A mutations are linked to postnatal epileptic encephalopathies, but prenatal features are poorly defined. We describe a novel SCN2A frameshift mutations prenatal phenotype and genotype–phenotype correlations. Case report A fetus with progressive cerebral anomalies underwent serial ultrasound, MRI, and whole-exome sequencing. Imaging showed persistent cavum septi pellucidi narrowing (0.9–2.6 mm at 21–30 weeks) and focal cortical thickening at the left temporoparietal junction. A de novo heterozygous SCN2A frameshift mutation (c.3043del, p.D1015Lfs*22) was identified, truncating Nav1.2 at residue 1015 and ablating critical functional domains. Protein modeling confirmed complete loss-of-function (LoF) due to α-subunit disruption. Conclusion This is the first report of prenatal imaging phenotypes in SCN2A frameshift mutations, featuring persistent CSP narrowing and progressive focal cortical thickening. Distinct from missense mutation-related ventriculomegaly, it suggests potential mutation-specific signatures. Unexplained CSP narrowing/cortical thickening warrants sodium channelopathy suspicion, with SCN2A prioritized in fetal cortical malformation panels. Single-case limitations demand large-cohort validation for genotype–phenotype correlations.