title: Severe Neonatal Epileptic Encephalopathy and KCNQ2 Mutation: Neuropathological Substrate?
abstract: BACKGROUND
  Neonatal convulsions are clinical manifestations in a heterogeneous group of disorders with different etiology and outcome. They are attributed to several genetic causes.
  
  
  METHODS
  We describe a patient with intractable neonatal seizures who died from respiratory compromise during a status epilepticus.
  
  
  RESULTS
  This case report provides electroencephalogram (EEG), MRI, genetic analysis, and neuropathological data. Genetic analysis revealed a de novo heterozygous missense mutation in the KCNQ2 gene, which encodes a subunit of a voltage-gated potassium channel. KCNQ2 gene mutation is associated with intractable neonatal seizures. EEG, MRI, data as well as mutation analysis have been described in other KCNQ2 cases. Post-mortem neuropathological investigation revealed mild malformation of cortical development with increased heterotopic neurons in the deep white matter compared to an age-matched control subject. The new finding of this study is the combination of a KCNQ2 mutation and the cortical abnormalities.
  
  
  CONCLUSIONS
  KCNQ2 mutations should be considered in neonates with refractory epilepsy of unknown cause. The mild cortical malformation is an important new finding, though it remains unknown whether these cortical abnormalities are due to the KCNQ2 mutation or are secondary to the refractory seizures.
authors.affiliation: Department of Neonatology, VU University Medical Center , Amsterdam , Netherlands.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Dalen Meurs-van der Schoor
authors.affiliation: Department of Neonatology, VU University Medical Center , Amsterdam , Netherlands.
authors.forename: Mirjam
authors.initials: M
authors.lastname: van Weissenbruch
authors.affiliation: Department of Medical Genetics, University Medical Center , Utrecht , Netherlands.
authors.forename: Marjan
authors.initials: M
authors.lastname: van Kempen
authors.affiliation: Department of Pathology, Neuroscience Campus Amsterdam, VU University Medical Center , Amsterdam , Netherlands ; Department of Child Neurology, Neuroscience Campus Amsterdam, VU University Medical Center , Amsterdam , Netherlands.
authors.forename: Marianna
authors.initials: M
authors.lastname: Bugiani
authors.affiliation: Department of Pathology, Academic Medical Center , Amsterdam , Netherlands.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Aronica
authors.affiliation: Department of Clinical Neurophysiology, VU University Medical Center , Amsterdam , Netherlands.
authors.forename: Hanneke
authors.initials: H
authors.lastname: Ronner
authors.affiliation: Department of Child Neurology, Neuroscience Campus Amsterdam, VU University Medical Center , Amsterdam , Netherlands.
authors.forename: R Jeroen
authors.initials: RJ
authors.lastname: Vermeulen
keywords: KCNQ2 mutation; MRI; cortical dysplasia; ion channel gene defect; neonatal; neonatal seizures