title: Epileptic encephalopathy in a girl with an interstitial deletion of Xp22 comprising promoter and exon 1 of the CDKL5 gene.
abstract: We report a 2-year-old girl with early onset seizures variant of Rett syndrome with a deletion at Xp22 detected by multiplex ligation-dependent probe amplification (MLPA) technique. This patient presented with tonic seizures at 7 days of life. Subsequently, she developed infantile spasms at three months and finally refractory myoclonic epilepsy. She demonstrated severe encephalopathy with hypotonia, deceleration of head growth, with eye gaze but limited eye pursuit, no language, limited hand use, and intermittent hand stereotypies. This combination of clinical features, suggestive of early onset variant of Rett syndrome led us to screen the CDKL5 gene. In a first step, screening of the whole coding sequence of the CDKL5 gene revealed no point mutations. In a second step, we searched gross rearrangements by MLPA and identified a microdeletion affecting both the promoter and exon 1 in CDKL5. Subsequent analysis on a Nimblegen HD2 microarray confirmed a deletion of approximately 300 kb at Xp22, including the BEND2, SCML2, and CDKL5 genes. In conclusion, our report suggests that searching for large rearrangements in CDKL5 should be considered in girls with early onset seizures and Rett-like features.
authors.affiliation: Service de Neurologie Pédiatrique, Département de Pédiatrie, Hôpital Necker Enfants Malades, AP-HP, Paris, France.
authors.forename: Nadia
authors.initials: N
authors.lastname: Bahi-Buisson
authors.forename: Benoit
authors.initials: B
authors.lastname: Girard
authors.forename: Agnes
authors.initials: A
authors.lastname: Gautier
authors.forename: Juliette
authors.initials: J
authors.lastname: Nectoux
authors.forename: Yann
authors.initials: Y
authors.lastname: Fichou
authors.forename: Yoann
authors.initials: Y
authors.lastname: Saillour
authors.forename: Karine
authors.initials: K
authors.lastname: Poirier
authors.forename: Jamel
authors.initials: J
authors.lastname: Chelly
authors.forename: Thierry
authors.initials: T
authors.lastname: Bienvenu
mesh_terms: D001927:Brain Diseases / Q000150:complications / Q000235:genetics*; D002675:Child, Preschool; D002872:Chromosome Deletion; D041321:Chromosomes, Human, X; D004827:Epilepsy / Q000150:complications / Q000235:genetics*; D005091:Exons; D005260:Female; D006801:Humans; D011401:Promoter Regions, Genetic; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*
chemical_list: D017346:Protein Serine-Threonine Kinases; C114482:CDKL5 protein, human