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The spectrum of epilepsy caused by POLG mutations

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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.

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Ethical approval

The study was approved by the ethical committee of University Hospitals Leuven.

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    Authors and Affiliations

    1. Department of Neurology, University Hospitals Leuven, Herestraat 49, 3000, Louvain, Belgium

      Wouter Janssen, Annelies Quaegebeur, Rik Vandenberghe & Wim Van Paesschen

    2. Neurogenetics Group, Department of Molecular Genetics, VIB, Antwerp, Belgium

      Gert Van Goethem & Katrien Smets

    3. Laboratory of Neurogenetics, Institute Born-Bunge, Antwerp, Belgium

      Gert Van Goethem, Löfgren Ann & Katrien Smets

    4. University of Antwerpen, Antwerp, Belgium

      Gert Van Goethem, Löfgren Ann & Katrien Smets

    5. Department of Neurology, University Hospital Antwerpen, Antwerp, Belgium

      Gert Van Goethem & Katrien Smets

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    1. Wouter Janssen
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    2. Annelies Quaegebeur
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    3. Gert Van Goethem
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    4. Löfgren Ann
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    7. Wim Van Paesschen
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    Correspondence to Wim Van Paesschen.

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    W. Janssen and A. Quaegebeur have equally contributed.

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    Janssen, W., Quaegebeur, A., Van Goethem, G. et al. The spectrum of epilepsy caused by POLG mutations. Acta Neurol Belg 116, 17–25 (2016). https://doi.org/10.1007/s13760-015-0499-8

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    • DOI: https://doi.org/10.1007/s13760-015-0499-8

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