A novel de novo SCN8A mutation in an Italian child treated with Levetiracetam: a case in discussion

We report on a 19-months-old girl, with early onset afebrile seizures and mild developmental delay. She presented with afebrile generalized tonicclonic seizures, after the first vaccination (Hexavalent vaccination, 5 months-old). She was referred to a child neurologist and treated with phenobarbital. The patients underwent neurological follow-up from 5 to 18 months of age. Seizures were not controlled and mild developmental delay was evident. At the age of 19 months, she presented with convulsive status epilepticus and treated with 35 mg of endorectal diazepam before admission, with subsequent cardiorespiratory failure. She was admitted to the intensive care unit of our hospital. Interictal awake electroencephalogram (EEG) showed: activity of continuous di used theta waves with sporadic Frontal focal spikes. After 13 days in intensive care unit the patient was moved to our child neurology ward, where she presented in a sleepiness state. EEG showed the presence of independent multifocal sharp waves, mostly frontal, epileptogenic abnormalities. Brain magnetic resonance imaging revealed no significant abnormalities, only mild cerebral atrophy. Due to the persistence of diffuse slowing at the EEG, an immune encephalopathy was suspected and, Dexamethasone and Immunoglobulin therapy was performed, without benefit. When the patient was seizure-free, she was discharged with Phenobarbital and Levetiracetam therapy (started in Intensive care unit). Twenty days later, at the follow-up in our Unit, the infant was significantly improved (after 3 weeks the patient was seizurefree, neurological examination showed marked improvement of gait stability and motor coordination. Next generation sequence analysis showed a heterozygous mutation (c.4423G>A (p.Gly1475 Arg) in the SCN8A gene (Chromosome 12q13). No further seizures occurred for 3 months. Conclusion: This report reviewed the clinical features of a patient with a de novo SCN8A mutation. Our data suggest that therapy with Phenobarbital and Levetiracetam could be effective in treating refractory epilepsy in a case with a SCN8A (c.4423G>A (p.Gly1475Arg) mutation.