SCN8A p.Arg1872Gln mutation in early infantile epileptic encephalopathy type 13: Review and case report

Early infantile epileptic encephalopathy (EIEE) is a disorder with variable genetic heterogeneity. Symptoms are mostly presented with generalised epileptic seizures with an infantile onset and progressive neurodevelopmental delay. Early infantile epileptic encephalopathy13 is caused by mutations in the SCN8A gene, which encodes the neuronal voltage-gated sodium channel α subunit (Nav1.6) and plays a major role in neuronal excitability. Describing the wide clinical variability of previously reported cases of patients carrying the same mutation, we demonstrate the complexity of the disease and the necessity of correctly correlating the phenotype with the genotype. Here, we present a minireview and a case report of EIEE13 involving the rare p.Arg1872Gln mutation in the SCN8A gene. We used targeted next-generation sequencing to examine a six-year-old girl with complex partial seizures from the left temporal lobe since 4 months of age. The condition was difficult to control with medication and the seizures evolved to generalised tonic-clonic seizures after the age of 3 years. Neurodevelopment in the child became severely delayed although seizures were as rare as 1 in every 5–10 months. А heterozygous missense mutation in the SCN8A gene (NM_014191.3:c.5616G > A, NP_055006.1:p.Arg1872Gln) was found. The variant was validated by Sanger sequencing. We suggest that this SCN8A mutation has a primary neurodegenerative effect leading to brain atrophy and intellectual disability (with or without autism) that is partially independent of its epileptogenic effect. Our results demonstrate that the application of large panels with clinically-associated genes is essential for identifying rare mutations in individuals with disorders of unknown etiology