title: Electroclinical pattern in MECP2 duplication syndrome: eight new reported cases and review of literature.
abstract: OBJECTIVE
  Duplications encompassing the MECP2 gene on the Xq28 region have been described in male patients with moderate to severe mental retardation, absent speech, neonatal hypotonia, progressive spasticity and/or ataxia, recurrent severe respiratory infections, gastrointestinal problems, mild facial dysmorphisms (midface hypoplasia, depressed nasal bridge, large ears) and epilepsy. Epilepsy can occur in >50% of cases, but the types of seizures and the electroclinical findings in affected male individuals have been poorly investigated up to the present. Herein we describe eight patients with MECP2 duplication syndrome and a specific clinical and electroencephalographic pattern.
  
  
  METHODS
  Array CGH of genomic DNA from the probands was performed, and an Xq28 duplication ranging from 209 kb to 6.36 Mb was found in each patient. Electroencephalography studies and clinical and seizure features of all the patients were analyzed.
  
  
  RESULTS
  We found that epilepsy tended to occur between late childhood and adolescence. Episodes of loss of tone of the head and/or the trunk were the most represented seizure types. Generalized tonic-clonic seizures were rarely observed. The typical interictal EEG pattern showed abnormal background activity, with generalized slow spike and wave asynchronous discharge with frontotemporal predominance. Sleep electroencephalography studies also demonstrated abnormal background activity; spindles and K complex were often abnormal in morphology and amplitude. Response to therapy was generally poor and drug resistance was a significant feature.
  
  
  CONCLUSIONS
  Although these cases and a review of the literature indicate that epilepsy associated with MECP2 duplication syndrome cannot be considered a useful marker for early diagnosis, epilepsy is present in >90% of adolescent patients and shows a peculiar electroclinical pattern. Consequently, it should be considered a significant sign of the syndrome, and an EEG follow-up of these patients should be encouraged from early childhood. Moreover, the definition of a more specific epileptic phenotype could be useful in order to suspect MECP2 duplication syndrome in older undiagnosed patients.
authors.affiliation: Epilepsy Center, San Paolo Hospital, Department of Medicine, Surgery and Dentistry, University of Milan, Milan, Italy. aglaia.vignoli@ao-sanpaolo.it
authors.forename: Aglaia
authors.initials: A
authors.lastname: Vignoli
authors.forename: Renato
authors.initials: R
authors.lastname: Borgatti
authors.forename: Angela
authors.initials: A
authors.lastname: Peron
authors.forename: Claudio
authors.initials: C
authors.lastname: Zucca
authors.forename: Lucia
authors.initials: L
authors.lastname: Ballarati
authors.forename: Clara
authors.initials: C
authors.lastname: Bonaglia
authors.forename: Melissa
authors.initials: M
authors.lastname: Bellini
authors.forename: Lucio
authors.initials: L
authors.lastname: Giordano
authors.forename: Romina
authors.initials: R
authors.lastname: Romaniello
authors.forename: Maria Francesca
authors.initials: MF
authors.lastname: Bedeschi
authors.forename: Roberta
authors.initials: R
authors.lastname: Epifanio
authors.forename: Silvia
authors.initials: S
authors.lastname: Russo
authors.forename: Rossella
authors.initials: R
authors.lastname: Caselli
authors.forename: Daniela
authors.initials: D
authors.lastname: Giardino
authors.forename: Francesca
authors.initials: F
authors.lastname: Darra
authors.forename: Francesca
authors.initials: F
authors.lastname: La Briola
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Banderali
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Canevini
mesh_terms: D000293:Adolescent; D000328:Adult; D058256:Brain Waves / Q000502:physiology*; D002648:Child; D002675:Child, Preschool; D004569:Electroencephalography; D004827:Epilepsy / Q000235:genetics* / Q000503:physiopathology*; D005260:Female; D020131:Genes, Duplicate / Q000235:genetics*; D056726:Genetic Association Studies; D006801:Humans; D008297:Male; D051783:Methyl-CpG-Binding Protein 2 / Q000235:genetics*; D055815:Young Adult
chemical_list: C497392:MECP2 protein, human; D051783:Methyl-CpG-Binding Protein 2