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KCNQ2 encephalopathy: Emerging phenotype of a neonatal epileptic encephalopathy
Author(s) -
Weckhuysen Sarah,
Mandelstam Simone,
Suls Arvid,
Audenaert Dominique,
Deconinck Tine,
Claes Lieve R.F.,
Deprez Liesbet,
Smets Katrien,
Hristova Dimitrina,
Yordanova Iglika,
Jordanova Albena,
Ceulemans Berten,
Jansen An,
Hasaerts Danièle,
Roelens Filip,
Lagae Lieven,
Yendle Simone,
Stanley Thorsten,
Heron Sarah E.,
Mulley John C.,
Berkovic Samuel F.,
Scheffer Ingrid E.
Publication year - 2012
Publication title -
annals of neurology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.764
H-Index - 296
eISSN - 1531-8249
pISSN - 0364-5134
DOI - 10.1002/ana.22644
Subject(s) - epilepsy , medicine , encephalopathy , electroencephalography , hyperintensity , pediatrics , psychomotor retardation , phenotype , magnetic resonance imaging , pathology , genetics , psychiatry , biology , radiology , alternative medicine , gene
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. Interpretation: 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