Work

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

Year: 2026

Type: article

Abstract: 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.

Source: Frontiers in Neuroscience

DOI: 10.3389/fnins.2026.1698102

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

Institutions: Ningbo University, Women's Hospital, School of Medicine, Zhejiang University, Zhejiang University

Language: English

Topic: Fetal and Pediatric Neurological Disorders

Subfield: Pediatrics, Perinatology and Child Health

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801