Targeted Therapy of GRIA1-Related Epilepsy and Intellectual Disability With Perampanel: A Case Report and Literature...

This report details a patient with a GRIA1 pathogenic variant presenting with intellectual disability (ID) and epilepsy. We describe clinical features, genetic findings, a personalized treatment approach, and a literature review of GRIA1-related disorders.

We describe clinical presentation, neuropsychological assessment, and genetic analysis. We conducted a literature review of published GRIA1-related disorders using PubMed, Simons Foundation Autism Research Initiative (SFARI) Gene, and ClinVar databases.

An 8-year-old girl with ID, focal-to-bilateral tonic clonic seizure since age 5, and later atypical absences was diagnosed with a novel, de novo GRIA1 c.2530T > G, p.Leu844Val pathogenic variant. After genetic diagnosis, she was titrated to 4 mg of perampanel, an α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antagonist, which led to seizure control and improvements in cognition and school performance. Literature review identified 31 patients carrying 15 different pathogenic variants. The c.1906G > A, p.Ala636Thr variant was recurrent in 17 individuals. Intellectual disability and autism spectrum disorder were common while epilepsy was reported in approximately a quarter of patients. Two patients with gain-of-function missense variants in GRIA1 and GRIA2, successfully treated with perampanel, have also been reported.

This case emphasizes the role of targeted interventions in the management of rare genetic disorders and underscores the potential of precision medicine in addressing GRIA1-related symptoms.