title: KCNQ2 encephalopathy: emerging phenotype of a neonatal epileptic encephalopathy.
abstract: OBJECTIVE
  KCNQ2 and KCNQ3 mutations are known to be responsible for benign familial neonatal seizures (BFNS). A few reports on patients with a KCNQ2 mutation with a more severe outcome exist, but a definite relationship has not been established. In this study we investigated whether KCNQ2/3 mutations are a frequent cause of epileptic encephalopathies with an early onset and whether a recognizable phenotype exists.
  
  
  METHODS
  We analyzed 80 patients with unexplained neonatal or early-infantile seizures and associated psychomotor retardation for KCNQ2 and KCNQ3 mutations. Clinical and imaging data were reviewed in detail.
  
  
  RESULTS
  We found 7 different heterozygous KCNQ2 mutations in 8 patients (8/80; 10%); 6 mutations arose de novo. One parent with a milder phenotype was mosaic for the mutation. No KCNQ3 mutations were found. The 8 patients had onset of intractable seizures in the first week of life with a prominent tonic component. Seizures generally resolved by age 3 years but the children had profound, or less frequently severe, intellectual disability with motor impairment. Electroencephalography (EEG) at onset showed a burst-suppression pattern or multifocal epileptiform activity. Early magnetic resonance imaging (MRI) of the brain showed characteristic hyperintensities in the basal ganglia and thalamus that later resolved.
  
  
  CONCLUSIONS
  KCNQ2 mutations are found in a substantial proportion of patients with a neonatal epileptic encephalopathy with a potentially recognizable electroclinical and radiological phenotype. This suggests that KCNQ2 screening should be included in the diagnostic workup of refractory neonatal seizures of unknown origin.
authors.affiliation: Neurogenetics Group, VIB-Department of Molecular Genetics, University of Antwerp, Antwerp, Belgium.
authors.forename: Sarah
authors.initials: S
authors.lastname: Weckhuysen
authors.forename: Simone
authors.initials: S
authors.lastname: Mandelstam
authors.forename: Arvid
authors.initials: A
authors.lastname: Suls
authors.forename: Dominique
authors.initials: D
authors.lastname: Audenaert
authors.forename: Tine
authors.initials: T
authors.lastname: Deconinck
authors.forename: Lieve R F
authors.initials: LR
authors.lastname: Claes
authors.forename: Liesbet
authors.initials: L
authors.lastname: Deprez
authors.forename: Katrien
authors.initials: K
authors.lastname: Smets
authors.forename: Dimitrina
authors.initials: D
authors.lastname: Hristova
authors.forename: Iglika
authors.initials: I
authors.lastname: Yordanova
authors.forename: Albena
authors.initials: A
authors.lastname: Jordanova
authors.forename: Berten
authors.initials: B
authors.lastname: Ceulemans
authors.forename: An
authors.initials: A
authors.lastname: Jansen
authors.forename: Danièle
authors.initials: D
authors.lastname: Hasaerts
authors.forename: Filip
authors.initials: F
authors.lastname: Roelens
authors.forename: Lieven
authors.initials: L
authors.lastname: Lagae
authors.forename: Simone
authors.initials: S
authors.lastname: Yendle
authors.forename: Thorsten
authors.initials: T
authors.lastname: Stanley
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Heron
authors.forename: John C
authors.initials: JC
authors.lastname: Mulley
authors.forename: Samuel F
authors.initials: SF
authors.lastname: Berkovic
authors.forename: Ingrid E
authors.initials: IE
authors.lastname: Scheffer
authors.forename: Peter
authors.initials: P
authors.lastname: de Jonghe
mesh_terms: D002648:Child; D002675:Child, Preschool; D020936:Epilepsy, Benign Neonatal / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D005260:Female; D006801:Humans; D051658:KCNQ2 Potassium Channel / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D010641:Phenotype
chemical_list: D051658:KCNQ2 Potassium Channel; C496914:KCNQ2 protein, human