Neurodevelopmental Disorder Due to a Frameshift Mutation in the GRIN2A Gene: A Case Report and Literature Review

Background: The GRIN2A gene is known to harbor rare mutations that can lead to neurodevelopmental disorders with diverse phenotypic presentations. This report describes a previously unreported case of a rare condition that initially presented with ataxia, followed by speech impairments without seizures, and showed subsequent improvement following immunotherapy. Case presentation: A 23-month-old male patient initially presented with ataxia. Despite the exclusion of autoimmune encephalitis, a definitive diagnosis remained undetermined. After undergoing immunotherapy, the patient experienced temporary symptom relief. However, he later developed speech impairment, drooling, and developmental regression, without seizures. Electroencephalogram (EEG) findings revealed abnormal patterns during sleep. Whole-genome sequencing identified a frameshift mutation in the GRIN2A gene (c.1717delG, p.Val573Phefs*16), which encodes a subunit of the N-methyl-D-aspartate (NMDA) receptor, essential for excitatory neurotransmission in the central nervous system. Following treatment with corticosteroids and immunoglobulin, the patient showed improvements in ataxic gait, cessation of drooling, and a significant reduction in abnormal EEG discharges. Conclusions: This report broadens the phenotypic spectrum associated with GRIN2A mutations and proposes a promising treatment strategy.