Developmental encephalopathy concomitant with aphasia associated with a pathogenic variant in the GRIN2A gene

Abstract

Mutations in the GRIN gene family, which encode subunits of the NMDA (N-methyl-D-aspartate) receptor, have been increasingly associated with a spectrum of neurodevelopmental disorders. Among them, GRIN2A mutations play a crucial regulatory role in the receptor's function, affecting synaptic transmission and brain plasticity. This case study presents the clinical and genetic profile of a pediatric patient with a pathogenic GRIN2A mutation, highlighting the associated neurological phenotype, diagnostic process, and treatment approach. Clinical data were collected through neurological assessments, EEG, MRI, and comprehensive genetic testing, including next-generation sequencing (NGS), with confirmation by Sanger sequencing. The patient's symptoms, including developmental delay, epileptic episodes, and behavioral abnormalities, were analyzed in the context of current literature on GRIN-related disorders The identified pathogenic GRIN2A mutation correlated with a neurodevelopmental phenotype characterized by early-onset epilepsy, hypotonia, and intellectual disability. The above case highlights the importance of early genetic testing in children with neurodevelopmental disorders and aphasia, as well as co-occurring epilepsy. Understanding the functional impact of specific GRIN2A mutations can guide personalized treatment strategies and contribute to a better characterization of the GRINopathy spectrum.