POLG1 mutations cause a syndromic epilepsy with occipital lobe predilection

Brain. 2008 Mar;131(Pt 3):818-28. doi: 10.1093/brain/awn007. Epub 2008 Jan 30.

Abstract

The epileptic semiology of 19 patients (from 15 families) with mitochondrial disease due to mutations in the POLG1 gene is presented. The patients were either homozygous for the 1399G > A (p.A467T) or 2243G > C (p.W748S) mutations or compound heterozygotes for these two mutations. While the clinical features have been reviewed, detailed analysis of their epilepsy is presented for the first time. Irrespective of genotype, patients developed an epileptic syndrome with initial features of occipital lobe epilepsy. Occipital seizure phenomena included flickering coloured light, sometimes persisting for weeks, months or even years, ictal visual loss, horizontal/vertical nystagmus or oculoclonus, dysmorphopsia, micro-/macropsia and palinopsia. Most patients developed simple partial seizure phenomena with motor symptoms suggesting frontal lobe seizure initiation or spread. Simple and complex partial seizures, clonic- and/or myoclonic seizures with epilepsia partialis continua and frequent convulsive status epilepticus were observed in this syndrome that appears to be a symptomatic and secondary generalized or multifocal epilepsy with focal occipital predilection. The mean age of seizure presentation was 18.4 years (6-58 years). All patients developed status epilepticus and 11 patient deaths were, all related to prolonged convulsive status epilepticus, including two with liver failure apparently precipitated by treatment with sodium valproate.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Age of Onset
  • Anticonvulsants / therapeutic use
  • Brain / pathology
  • Child
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase / genetics*
  • Disease Progression
  • Electroencephalography
  • Epilepsies, Partial / drug therapy
  • Epilepsies, Partial / etiology
  • Epilepsies, Partial / genetics*
  • Epilepsies, Partial / pathology
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Mitochondrial Diseases / complications
  • Mitochondrial Diseases / genetics*
  • Mutation*
  • Prognosis
  • Status Epilepticus / etiology
  • Status Epilepticus / genetics
  • Status Epilepticus / pathology
  • Syndrome

Substances

  • Anticonvulsants
  • DNA Polymerase gamma
  • DNA-Directed DNA Polymerase
  • POLG protein, human