FARS2 (phenylalanyl-tRNA synthetase 2) deficiency: A novel mutation associated with EEG phenotype of epilepsy of infancy with migrating focal seizures (EIMFS)

Epilepsy of infancy with migrating focal seizures (EIMFS) is a rare devastating infantile epileptic encephalopathy that is characterized by a unique electroencephalopgraphy (EEG) signature of multifocal simultaneous seizures. Although no definite etiology is understood for EIMFS, mutations in certain ion channels, are implicated. Similarly, phenylalanyl-tRNA synthetase 2 (FARS2) deficiency is a rare, autosomal recessive disorder of dysfunctional mitochondrial translation causing refractory seizures, lactic acidosis, and developmental regression with a variety of EEG findings. However, an EIMFS-like pattern on EEG in FARS2 deficiency has only recently been reported once. Herein, we describe a seven-week-old male with seizures where whole exome sequencing (WES) revealed pathogenic FARS2 variants and an EIMFS pattern on EEG. This case provides an insight on a novel genetic mechanism for EIMFS. We encourage early consideration of WES when EIMFS is detected to evaluate for FARS2 deficiency, especially in the setting of profound lactic acidosis.