Purpose To review our clinical experience and determine if there are appropriate signs and symptoms to consider POLG sequencing prior to valproic acid (VPA) dosing in patients with seizures. Methods Four patients who developed VPA-induced hepatotoxicity were examined for POLG sequence variations. A subsequent chart review was used to describe clinical course prior to and after VPA dosing. Results Four patients of multiple different ethnicities, age 3–18 years, developed VPA-induced hepatotoxicity. All were given VPA due to intrac partial seizures. Three of the patients had developed epilepsia partialis continua. The time from VPA exposure to liver failure was between 2 and 3 months. Liver failure was reversible in one patient. Molecular studies revealed homozygous p.R597W or p.A467T mutations in two patients. The other two patients showed compound heterozygous mutations, p.A467T/p.Q68X and p.L83P/p.G888S. Clinical findings and POLG mutations were diagnostic of Alpers–Huttenlocher syndrome. Conclusion Our cases underscore several important findings: POLG mutations have been observed in every ethnic group studied to date; early predominance of epileptiform discharges over the occipital region is common in POLG-induced epilepsy; the EEG and MRI findings varying between patients and stages of the disease; and VPA dosing at any stage of Alpers–Huttenlocher syndrome can precipitate liver failure. Our data support an emerging proposal that POLG gene testing should be considered in any child or adolescent who presents or develops intractable seizures with or without status epilepticus or epilepsia partialis continua, particularly when there is a history of psychomotor regression.

KCNQ2 mutations can cause benign familial neonatal convulsions (BFNC), benign familiar infantile convulsions (BFIC), and neonatal epileptic encephalopathy. KCNQ2-associated seizures usually manifest during the first week of life. Some affected children will have recurrent febrile seizures, benign childhood epilepsy with centrotemporal spikes (BCECTS), or idiopathic generalized epilepsy on follow-up. However, the outcomes in these patients cannot be accurately predicted. We reviewed the phenotypes, and genotypes of the KCNQ2 mutation, pathophysiological mechanisms and drug treatments for KCNQ2-associated epilepsy. We conclude that KCNQ2 mutations can cause various epileptic phenotypes and different neurodevelopmental outcomes in children.

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Objective: Electroencephalographic suppression bursts (SBs) in newborns usually indicate a grave neurodevelopmental syndrome; however, they have heterogeneous etiologies and noteworthy phenotypes and outcomes. Methods:We studied 22 newborns with electroencephalographic SBs with varied etiologies, electroencephalographic evolution, associated changes of seizure semiology, and neurodevelopmental outcomes.