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The three stages of epilepsy in patients with CDKL5 mutations
Author(s) -
BahiBuisson Nadia,
Kaminska Anna,
Boddaert Nathalie,
Rio Marlène,
Afenjar Alexandra,
Gérard Marion,
Giuliano Fabienne,
Motte Jacques,
Héron Delphine,
Morel Marie Ange N'Guyen,
Plouin Perrine,
Richelme Christian,
Des Portes Vincent,
Dulac Olivier,
Philippe Christophe,
Chiron Catherine,
Nabbout Rima,
Bienvenu Thierry
Publication year - 2008
Publication title -
epilepsia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.687
H-Index - 191
eISSN - 1528-1167
pISSN - 0013-9580
DOI - 10.1111/j.1528-1167.2007.01520.x
Subject(s) - epilepsy , hypsarrhythmia , ictal , genotype , dravet syndrome , encephalopathy , mutation , pediatrics , phenotype , west syndrome , electroencephalography , epilepsy syndromes , medicine , epileptic spasms , biology , genetics , psychiatry , gene
SummaryMutations in the X‐linked cyclin‐dependent kinase‐like 5 ( CDKL5 ) gene are responsible for a severe encephalopathy with early epilepsy. So far, the electroclinical phenotype remains largely unknown and no clear genotype–phenotype correlations have been established.Purpose: To characterize the epilepsy associated with CDKL5 mutations and to look for a relationship between the genotype and the course of epilepsy.Methods : We retrospectively analyzed the electroclinical phenotypes of 12 patients aged from 2.5 to 19 years diagnosed with pathogenic CDKL5 mutations and one patient with a novel intronic sequence variation of uncertain pathogenicity and examined whether the severity of the epilepsy was linked to the type and location of mutations.Results : The epilepsy course reveals three successive stages: (Stage I) early epilepsy (onset 1–10 weeks) with normal interictal electroencephalogram (EEG) (10/13) despite frequent convulsive seizures; (Stage II) epileptic encephalopathy with infantile spasms (8/8) and hypsarrhythmia (8/8). At the age of evaluation, seven patients were seizure free and six had developed refractory epilepsy (stage III) with tonic seizures and myoclonia (5/6). Interestingly, the patients carrying a CDKL5 mutations causing a truncation of the catalytic domain tended to develop a more frequent refractory epilepsy than patients with mutations located downstream (4/6, 66.6% versus 1/6, 16%) although, these trends are not yet significant.Discussion : Our data contribute to a better definition of the epileptic phenotype in CDKL5 mutations, and might give some clues to a potential relationship between the phenotype and the genotype in these patients.