KCNQ2 encephalopathy: Emerging phenotype of a neonatal epileptic encephalopathy
Article first published online: 24 JAN 2012
Copyright © 2011 American Neurological Association
Annals of Neurology
Volume 71, Issue 1, pages 15–25, January 2012
How to Cite
Weckhuysen, S., Mandelstam, S., Suls, A., Audenaert, D., Deconinck, T., Claes, L. R.F., Deprez, L., Smets, K., Hristova, D., Yordanova, I., Jordanova, A., Ceulemans, B., Jansen, A., Hasaerts, D., Roelens, F., Lagae, L., Yendle, S., Stanley, T., Heron, S. E., Mulley, J. C., Berkovic, S. F., Scheffer, I. E. and Peter de Jonghe (2012), KCNQ2 encephalopathy: Emerging phenotype of a neonatal epileptic encephalopathy. Ann Neurol., 71: 15–25. doi: 10.1002/ana.22644
- Issue published online: 24 JAN 2012
- Article first published online: 24 JAN 2012
- Accepted manuscript online: 10 OCT 2011 10:45AM EST
- Manuscript Accepted: 30 SEP 2011
- Manuscript Revised: 25 SEP 2011
- Manuscript Received: 19 APR 2011
- Fund for Scientific Research Flanders (FWO)
- Methusalem excellence grant of the Flemish Government
- University of Antwerp
- Interuniversity Attraction Poles
- program P6/43 of the Belgian Science Policy Office (BELSPO)
- Eurocores program Euro EPINOMICS of the European Science Foundation
- National Health and Medical Research Council of Australia
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.
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.
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.
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. ANN NEUROL 2012;71:15–25