Perampanel therapy for intractable GRIN2D-related developmental and epileptic encephalopathy: A case report and literature review

Background: N-methyl-D-aspartate receptors (NMDARs) are ligand-gated ion channels that mediate excitatory synaptic trans-mission and brain development in the central nervous system. Mutations in GRIN2D encoding the NMDAR subunit GluN2D are associated with a wide spectrum of neurodevelopmental disorders. Methods: We report a novel de novo GRIN2D variant (NM_000836.2: c.2024C > T, p.Ala675Val) in an infant with severe devel-opmental and epileptic encephalopathy. Clinical characteristics and treatment outcomes of patients with GRIN2D-related develop-mental and epileptic encephalopathy were summarized by reviewing the literature. Results: In silico analysis suggested this p.Ala675Val variant residing in the highly conserved M3 helix of GluN2D would inter-fere with channel gating. Therapeutic options including multiple anticonvulsants, oral corticosteroid therapy, and ketogenic diet failed to achieve seizure control. Eventually, adjunctive therapy with perampanel led to marked electroclinical improvement. Conclusions: Perampanel can be beneficial adjuvant therapy for patients with GRIN2D-related intractable epilepsy. Mechanistic understanding and case-per-se analysis are required to enable more individualized treatment for the patients.(c) 2022 Published by Elsevier B.V. on behalf of The Japanese Society of Child Neurology. All rights reserved.