Divergent Presentation of GRIN2B Neurodevelopmental Disorder in Monozygotic Twins: Case Report with Unique Imaging...

We describe a set of monozygotic twins with Glutamate Ionotropic Receptor N-methyl-D-aspartate Type Subunit 2B-related neurodevelopmental disorder (GRIN2B-ND) who exhibited distinct clinical and imaging characteristics due to a de novo heterozygous pathogenic variant in the GRIN2B gene (c.2453T > C, p.Met818Thr). Twin A displayed extensive symmetric malformation of cortical development (MCD) resembling polymicrogyria, accompanied by shallow sulci, dilated lateral ventricles, and dysplastic appearances of the basal ganglia, corpus callosum, and hippocampi. In twin B, malformative features, such as reduced brain volume, MCD, shallow sulci, and dilated lateral ventricle, were confined to the left hemisphere. In combination with previously published data, our report highlights variable phenotypes associated with the p.(Met818Thr) pathogenic variant, specifically with a potential for asymmetric or even unilateral presentation. We discuss the potential interplay between genetic and environmental factors underlying this phenomenon within the context of monozygotic twins. In addition, we also highlight the importance of recognizing potential genetic underpinnings in the assessment of apparently unilateral brain malformations.