Investigators at Children's Hospital of Philadelphia, PA, report a 3-year-old female who had presented with seizures at 10 weeks of life. Seizures were characterized by brief episodes of eye deviation, lip smacking, and alternating unilateral motor activity. EEG showed focal sharp and slow waves in runs that migrate between left and right hemispheres and evolve into near-continuous seizures. Neurological and general physical examinations and brain MRI were normal. Whole exome sequencing demonstrated a heterozygous missense mutation in KCNT1, a mutation previously described in 3 patients with migrating partial seizures of infancy (MPSI). Trials of multiple conventional AEDs were without benefit, the ketogenic diet partially controlled seizures but was associated with regression of development, and a trial of quinidine was considered justified. After 1 week following the addition of quinidine to the AED polytherapy and ketogenic diet, seizures ceased and she was seizure-free for 6 weeks. Developmentally, head control improved and she spoke her first words. At the last follow-up, she had been seizure-free for >4 months, without adverse events. This case illustrates a novel approach to seizure treatment using a rapid identification of genetic mutation (in KCNT1) that can lead to targeted treatments (quinidine acts as a pore blocker, normalizing pathological potassium conductance in mutant KCNT1 channels). 
COMMENTARY. MPSI is an early onset epileptic encephalopathy characterized by randomly migrating focal seizures and psychomotor deterioration. Death, usually from intractable seizures or respiratory complications, often occurs within the first years of life . MPSI is associated with mutations in a variety of genes, most commonly KCNT1, a known target of some cardiac drugs, including quinidine. The authors caution that quinidine exhibits drug interactions, inhibiting the metabolism of many antiepileptic medications. QT prolongation is a common adverse effect, necessitating close EKG monitoring.