title: The spectrum of epilepsy caused by POLG mutations.
abstract: Mutations in POLG are increasingly recognized as a cause of refractory occipital lobe epilepsy (OLE) and status epilepticus (SE). Our aim was to describe the epilepsy syndrome in seven patients with POLG mutations. We retrospectively reviewed the medical records of seven patients with POLG mutations and epilepsy. Mutation analysis was performed by direct sequencing of the coding exons of the POLG gene. Disease onset was at a median age of 18 years (range 12-26). Epilepsy was the presenting problem in six patients. All had focal seizures, with motor (n = 6) and visual (n = 6) phenomena. Six patients had secondarily generalized seizures and two patients had myoclonic seizures. Six patients had one or more episodes of refractory SE, including focal (n = 5), subtle (n = 4), myoclonic (n = 2) and convulsive (n = 3) SE. During or after SE, brain MRI showed lesions affecting the occipital lobe in all patients, probably due to continuous epileptic activity. Five of the six patients with SE died during treatment of SE, one due to valproate-induced hepatotoxicity. Associated clinical symptoms were ataxia (n = 6), polyneuropathy (n = 6), progressive external ophthalmoplegia (PEO) (n = 3) and migraine (n = 3). Epilepsy may be the first and dominant neurological problem caused by POLG mutations. The epilepsy may be severe and the condition of the patient may end in fatal SE. Refractory OLE and SE in a patient with polyneuropathy, ataxia, PEO or migraine warrant screening for POLG mutations. In this clinical setting, valproate should not be given in view of the risk of fatal hepatotoxicity.
authors.affiliation: Department of Neurology, University Hospitals Leuven, Herestraat 49, 3000, Louvain, Belgium. wouter.janssen@uzleuven.be.
authors.forename: Wouter
authors.identifier: http://orcid.org/0000-0001-8921-2429
authors.initials: W
authors.lastname: Janssen
authors.affiliation: Department of Neurology, University Hospitals Leuven, Herestraat 49, 3000, Louvain, Belgium.
authors.forename: Annelies
authors.initials: A
authors.lastname: Quaegebeur
authors.affiliation: Neurogenetics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.|Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium.|University of Antwerpen, Antwerp, Belgium.|Department of Neurology, University Hospital Antwerpen, Antwerp, Belgium.
authors.forename: Gert
authors.initials: G
authors.lastname: Van Goethem
authors.affiliation: Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium.|University of Antwerpen, Antwerp, Belgium.
authors.forename: Löfgren
authors.initials: L
authors.lastname: Ann
authors.affiliation: Neurogenetics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium.|Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium.|University of Antwerpen, Antwerp, Belgium.|Department of Neurology, University Hospital Antwerpen, Antwerp, Belgium.
authors.forename: Katrien
authors.initials: K
authors.lastname: Smets
authors.affiliation: Department of Neurology, University Hospitals Leuven, Herestraat 49, 3000, Louvain, Belgium.
authors.forename: Rik
authors.initials: R
authors.lastname: Vandenberghe
authors.affiliation: Department of Neurology, University Hospitals Leuven, Herestraat 49, 3000, Louvain, Belgium. wim.vanpaesschen@uzleuven.be.
authors.forename: Wim
authors.initials: W
authors.lastname: Van Paesschen
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004252:DNA Mutational Analysis; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D004569:Electroencephalography; D004827:Epilepsy / Q000175:diagnosis / Q000000981:diagnostic imaging / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D019788:Fluorodeoxyglucose F18 / Q000493:pharmacokinetics; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation / Q000235:genetics*; D049268:Positron-Emission Tomography; D055815:Young Adult
chemical_list: D019788:Fluorodeoxyglucose F18; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human
keywords: Mitochondrial disease; POLG; Status epilepticus; Valproate