Background: Febrile Infection-Related Epilepsy Syndrome (FIRES) is a catastrophic condition characterized by a refractory status epilepticus following a febrile illness in normally developing children. Many attempts to find the related genes have been tried without success. This study was aimed to evaluate its clinical and genetic characteristics.

Method: Fifteen patients with FIRES were involved in the study. Their clinical features, lab findings, treatment and outcome were retrospectively reviewed. We also performed whole exome sequencing on 5 out of the subjects. Among hundreds of epilepsy candidate genes, rare (<0.5% in 1000 genomes population), nonsynonymous, loss-of-function and splice-site variants were prioritized.

Results:  They initially presented with either partial seizures or partial seizures with secondary generalization. Half of the patients had pleocytosis in CSF. All patients showed diffuse slowing or epileptic discharges in various regions in EEG and normal on initial brain MRI. The mainstay therapy consists of phenytoin, midazolam drip and high dose phenobarbital during the acute phase. Patients who underwent whole exome sequencing revealed shared mutations in eleven genes, which are functionally important in various epilepsy syndromes. No significant variants were identified in SCN1A, PCDH19, POLG, or ABCB1.

Conclusions: Genetic analysis can be a valuable method for patients with febrile status epilepticus to predict its courses. Further knowledge about the pathogenesis and identification of the molecular/regulatory pathways in FIRES will enable the optimal target to the therapeutic potential of genetic-based drugs.