Abstract
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.
Keywords
GRIN2B-related neurodevelopmental disorder -
GRIN2B gene - monozygotic twins - brain malformations - imaging - epilepsy
