Novel Pathogenic DCX Mutation in Male With Subcortical Band Heterotopia

Subcortical band heterotopia (SBH), also known as “double cortex syndrome,” is a rare neuronal migration disorder most commonly arising from mutations in the DCX gene. The DCX gene encodes doublecortin, a protein essential for normal neuronal migration during fetal brain development. Due to its X-linked inheritance, pathogenic variants in DCX typically lead to clinically distinct neurologic disorders between males and females.

We present a case of a 19-year-old male with a history of epilepsy and sudden death. Autopsy examination revealed diffuse gray matter heterotopia, leading to a diagnosis of subcortical band heterotopia. Postmortem genetic analysis identified a single amino acid deletion mutation in the DCX gene classified as a “variant of uncertain significance.” Based on the clinical presentation, autopsy findings, and genetic results, we propose that this specific variant be reclassified as likely pathogenic.