De novo mutations in the GRIN1 gene have been recently reported as the molecular cause of a broad-spectrum early-onset neurological phenotype. Here, we describe a five-year-old girl with an early-onset epileptic encephalopathy associated with an infantile hyperkinetic movement disorder and oculomotor abnormalities. Whole-exome sequencing identified a novel p.Met641Leu de novo variant in the GRIN1 gene as the cause of the phenotype. In silico analysis suggested that the p.Met641Leu variant would alter the gating property of the ion channel, with the involved methionine residue facing towards the ion pore. Long-term systematic video-EEG allowed us to report on the electroclinical history and, specifically, on the semiology of the hyperkinetic movement disorder and oculomotor abnormalities resembling oculogyric crises in our patient. Our findings and a review of the recent literature reinforce the notion of GRIN1-encephalopathy as a recognizable neurological phenotype that should be suspected in early-onset epilepsy associated with hyperkinetic movement disorders. [Published with video sequence on www.epilepticdisorders.com].
Keywords: GRIN1 gene; NMDA receptors; epileptic encephalopathy; hyperkinetic movements; oculogyric crisis.