Journal Article

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

Zhu, Linyan, Ding, Huiqing, Dong, Minyue, Chen, Mei

2026

Overview

mutations are linked to postnatal epileptic encephalopathies, but prenatal features are poorly defined. We describe a novel frameshift mutations prenatal phenotype and genotype-phenotype correlations. 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 heterozygous 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. This is the first report of prenatal imaging phenotypes in 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 prioritized in fetal cortical malformation panels. Single-case limitations demand large-cohort validation for genotype-phenotype correlations.

• Publisher: Frontiers Media SA,Frontiers Media S.A
• Subject: Case Report / cortical dysplasia / frameshift mutation / genotype–phenotype / prenatal diagnosis / SCN2A