Electroclinical pattern in MECP2 duplication syndrome: Eight new reported cases and review of literature

Aglaia Vignoli, Renato Borgatti, Angela Peron, Claudio Zucca, Lucia Ballarati, Clara Bonaglia, Melissa Bellini, Lucio Giordano, Romina Romaniello, Maria Francesca Bedeschi, Roberta Epifanio, Silvia Russo, Rossella Caselli, Daniela Giardino, Francesca Darra, Francesca La Briola, Giuseppe Banderali, Maria Paola Canevini

Research output: Contribution to journalArticle

Abstract

Purpose: 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. Key findings: 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. Significance: 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.

Original languageEnglish
Pages (from-to)1146-1155
Number of pages10
JournalEpilepsia
Volume53
Issue number7
DOIs
Publication statusPublished - Jul 2012

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Epilepsy
Electroencephalography
Seizures
Muscle Hypotonia
Ataxia
Lubs X-linked mental retardation syndrome
Nose
Drug Resistance
Intellectual Disability
Respiratory Tract Infections
Ear
Early Diagnosis
Sleep
Head
Phenotype
DNA
Genes
Therapeutics

Keywords

  • Chromosomal duplication
  • EEG pattern
  • Epilepsy
  • MECP2
  • X-linked mental retardation

ASJC Scopus subject areas

  • Clinical Neurology
  • Neurology

Cite this

Electroclinical pattern in MECP2 duplication syndrome : Eight new reported cases and review of literature. / Vignoli, Aglaia; Borgatti, Renato; Peron, Angela; Zucca, Claudio; Ballarati, Lucia; Bonaglia, Clara; Bellini, Melissa; Giordano, Lucio; Romaniello, Romina; Bedeschi, Maria Francesca; Epifanio, Roberta; Russo, Silvia; Caselli, Rossella; Giardino, Daniela; Darra, Francesca; La Briola, Francesca; Banderali, Giuseppe; Canevini, Maria Paola.

In: Epilepsia, Vol. 53, No. 7, 07.2012, p. 1146-1155.

Research output: Contribution to journalArticle

Vignoli, A, Borgatti, R, Peron, A, Zucca, C, Ballarati, L, Bonaglia, C, Bellini, M, Giordano, L, Romaniello, R, Bedeschi, MF, Epifanio, R, Russo, S, Caselli, R, Giardino, D, Darra, F, La Briola, F, Banderali, G & Canevini, MP 2012, 'Electroclinical pattern in MECP2 duplication syndrome: Eight new reported cases and review of literature', Epilepsia, vol. 53, no. 7, pp. 1146-1155. https://doi.org/10.1111/j.1528-1167.2012.03501.x
Vignoli, Aglaia ; Borgatti, Renato ; Peron, Angela ; Zucca, Claudio ; Ballarati, Lucia ; Bonaglia, Clara ; Bellini, Melissa ; Giordano, Lucio ; Romaniello, Romina ; Bedeschi, Maria Francesca ; Epifanio, Roberta ; Russo, Silvia ; Caselli, Rossella ; Giardino, Daniela ; Darra, Francesca ; La Briola, Francesca ; Banderali, Giuseppe ; Canevini, Maria Paola. / Electroclinical pattern in MECP2 duplication syndrome : Eight new reported cases and review of literature. In: Epilepsia. 2012 ; Vol. 53, No. 7. pp. 1146-1155.
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AU - Ballarati, Lucia

AU - Bonaglia, Clara

AU - Bellini, Melissa

AU - Giordano, Lucio

AU - Romaniello, Romina

AU - Bedeschi, Maria Francesca

AU - Epifanio, Roberta

AU - Russo, Silvia

AU - Caselli, Rossella

AU - Giardino, Daniela

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N2 - Purpose: 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. Key findings: 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. Significance: 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.

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