# 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

## TL;DR

A fetus with a rare SCN2A mutation showed unique brain imaging features, suggesting a new prenatal diagnosis approach for this genetic condition.

## Contribution

First prenatal imaging description of SCN2A frameshift mutation, linking imaging features to a loss-of-function genetic variant.

## Key findings

- Persistent cavum septi pellucidi narrowing and focal cortical thickening observed in prenatal imaging.
- De novo SCN2A frameshift mutation confirmed to cause loss-of-function in Nav1.2 sodium channels.
- Distinct imaging features suggest mutation-specific signatures in SCN2A-related cortical dysplasia.

## Abstract

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.

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.

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.