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The three stages of epilepsy in patients with CDKL5 mutations |
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| Authors: | Bahi-Buisson 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 |
| Affiliation: | Service de Neurologie Pédiatrique, Département de Pédiatrie, Hopital Necker Enfants Malades, AP-HP, Paris V, Paris, France;;Inserm, U663, Paris, France;UniversitéRenéDescartes, Paris V, France;;Centre de Reference pour les Epilepsies Rares de l'enfant, Hopital Necker Enfants Malades APHP, Paris, France;;Service de Neurophysiologie clinique, Hopital Necker Enfants Malades, AP-HP, Paris, France;;Service de Radiologie Pédiatrique, Hopital Necker Enfants Malades, AP-HP, Paris V, Paris, France;;U797- INSERM-CEA, Service Hospitalier Frédéric Joliot, CEA, 4, place du General Leclerc, 91406, Orsay, France;;Service de Génétique, Hopital Necker Enfants Malades, AP-HP, Paris, France;;Service de Neurologie Pédiatrique, Hopital Trousseau AP-HP, Paris, France;;Service de Génétique, Hopital Robert DebréAP-HP, Paris, France;;Service de Génétique, Centre Hospitalo-Universitaire, Nice, France;;Service de Neurologie Pédiatrique, Département de Pédiatrie, Hopital Américain de Reims, Reims, France;;Département de Génétique Groupe Hospitalier PitiéSalpêtrière Paris France;;Département de Pédiatrie, Centre du Langage et troubles des apprentissages, Centre Hospitalo-Universitaire, Grenoble, France;;Service de Neurologie Pédiatrique, Centre Hospitalo-Universitaire, Nice, France;;Service de Neurologie Pédiatrique, Centre Hospitalo-Universitaire de Lyon, France;, Laboratoire de Génétique Médicale, EA 4002, Centre Hospitalo-Universitaire Nancy-Brabois, Vandoeuvre les Nancy, France;;and Service de Biochimie et Génétique Moléculaire Hopital Cochin, et UniversitéRenéDescartes, Institut Cochin, Inserm U567, Paris, France |
| Abstract: | Mutations 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. |
| Keywords: | Epileptic encephalopathy Atypical Rett syndrome CDKL5 mutations Infantile spasms |
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