Oculogyric crisis induced by risperidone in a child withGRIN1variant

Abstract

The GluN1 subunit of the N-methyl-d-aspartate (NMDA) receptor is encoded by GRIN1 gene. Mutations in this gene can cause neurodevelopmental disorders with or without hyperkinetic movements and seizures. It can be inherited as either autosomal dominant (NDHMSD) or autosomal recessive (NDHMSR). Patients can present with severe psychomotor delay, seizures, behavioral problems, stereotypies, and oculogyric crisis (OGC). There is emerging evidence regarding the molecular interaction between dopamine and NMDA receptors, cross-talk between dopamine and glutamate signaling, and mutations in GRIN1 could affect both glutamatergic and dopaminergic synaptic transmission. Dopamine antagonists, such as risperidone, which is used to treat behavioral problems, can cause extrapyramidal side effects, including OGC. Here, we present a case of an 8-year-old boy with a GRIN1 variant who was treated with risperidone for severe behavioral problems and experienced an OGC for approximately 30 h. The child had no prior history of such event and experienced no re-occurrences after discontinuing risperidone. This case highlights the importance of exercising extra caution while prescribing dopamine antagonists for patients with GRIN1 mutations and reports the efficacy of memantine in treating seizures and behavioral side effects in such patients. In the era of precision medicine, this case represents a good example of how patient's genetic makeup should be considered in prescribing the right medication for the right patient.