title: The three stages of epilepsy in patients with CDKL5 mutations.
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.
  
  
  OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Département de Pédiatrie, Service de Neurologie Pédiatrique, Hopital Necker Enfants Malades, AP-HP, Paris V, Paris, France. nadia.bahi-buisson@nck.aphp.fr
authors.forename: Nadia
authors.initials: N
authors.lastname: Bahi-Buisson
authors.forename: Anna
authors.initials: A
authors.lastname: Kaminska
authors.forename: Nathalie
authors.initials: N
authors.lastname: Boddaert
authors.forename: Marlène
authors.initials: M
authors.lastname: Rio
authors.forename: Alexandra
authors.initials: A
authors.lastname: Afenjar
authors.forename: Marion
authors.initials: M
authors.lastname: Gérard
authors.forename: Fabienne
authors.initials: F
authors.lastname: Giuliano
authors.forename: Jacques
authors.initials: J
authors.lastname: Motte
authors.forename: Delphine
authors.initials: D
authors.lastname: Héron
authors.forename: Marie Ange N'guyen
authors.initials: MA
authors.lastname: Morel
authors.forename: Perrine
authors.initials: P
authors.lastname: Plouin
authors.forename: Christian
authors.initials: C
authors.lastname: Richelme
authors.forename: Vincent
authors.initials: V
authors.lastname: des Portes
authors.forename: Olivier
authors.initials: O
authors.lastname: Dulac
authors.forename: Christophe
authors.initials: C
authors.lastname: Philippe
authors.forename: Catherine
authors.initials: C
authors.lastname: Chiron
authors.forename: Rima
authors.initials: R
authors.lastname: Nabbout
authors.forename: Thierry
authors.initials: T
authors.lastname: Bienvenu
mesh_terms: D000293:Adolescent; D020134:Catalytic Domain / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D041321:Chromosomes, Human, X / Q000235:genetics*; D002908:Chronic Disease; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004569:Electroencephalography; D004831:Epilepsies, Myoclonic / Q000175:diagnosis / Q000235:genetics; D004827:Epilepsy / Q000175:diagnosis / Q000235:genetics*; D004829:Epilepsy, Generalized / Q000175:diagnosis / Q000235:genetics; D006580:Genetic Carrier Screening; D005838:Genotype; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007438:Introns / Q000235:genetics; D010641:Phenotype; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D012189:Retrospective Studies; D012729:Sex Chromosome Aberrations; D013036:Spasms, Infantile / Q000175:diagnosis / Q000235:genetics*
chemical_list: D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human