Further delineation and long-term evolution of electroclinical phenotype in Mowat Wilson Syndrome. A longitudinal study in 40 individuals: Epilepsy and Behavior

E. Ricci, A. Fetta, L. Garavelli, S. Caraffi, I. Ivanovski, P. Bonanni, P. Accorsi, L. Giordano, C. Pantaleoni, A. Romeo, A. Arena, S. Bonetti, A. Boni, D. Chiarello, V. Di Pisa, R. Epifanio, F. Faravelli, E. Finardi, A. Fiumara, D. GrioniI. Mammi, S. Negrin, E. Osanni, F. Raviglione, F. Rivieri, R. Rizzi, S. Savasta, L. Tarani, N. Zanotta, A. Dormi, A. Vignoli, M. Canevini, D.M. Cordelli, Mowat Wilson Epilepsy Study Group

Research output: Contribution to journalArticlepeer-review

Abstract

Background: Epilepsy is a main feature of Mowat Wilson Syndrome (MWS), a congenital malformation syndrome caused by ZEB2 variants. The aim of this study was to investigate the long-term evolution of the electroclinical phenotype of MWS in a large population. Methods: Forty-individuals with a genetically confirmed diagnosis were enrolled. Three age groups were identified (t1 = 0–4; t2 = 5–12; t3 = >13 years); clinical data and EEG records were collected, analyzed, and compared for age group. Video-EEG recorded seizures were reviewed. Results: Thirty-six of 40 individuals had epilepsy, of whom 35/35 aged >5 years. Almost all (35/36) presented focal seizures at onset (mean age at onset 3.4 ± 2.3 SD) that persisted, reduced in frequency, in 7/22 individuals after the age of 13. Absences occurred in 22/36 (mean age at onset 7.2 ± 0.9 SD); no one had absences before 6 and over 16 years old. Paroxysmal interictal abnormalities in sleep also followed an age-dependent evolution with a significant increase in frequency at school age (p = 0.002) and a reduction during adolescence (p = 0.008). Electrical Status Epilepticus during Sleep occurred in 14/36 (13/14 aged 5–13 years old at onset). Seven focal seizure ictal video-EEGs were collected: all were long-lasting and more visible clinical signs were often preceded by prolonged electrical and/or subtle (erratic head and eye orientation) seizures. Valproic acid was confirmed as the most widely used and effective drug, followed by levetiracetam. Conclusions: Epilepsy is a major sign of MWS with a characteristic, age-dependent, electroclinical pattern. Improvement with adolescence/adulthood is usually observed. Our data strengthen the hypothesis of a GABAergic transmission imbalance underlying ZEB2-related epilepsy. © 2021 Elsevier Inc.
Original languageEnglish
JournalEpilepsy Behav.
Volume124
DOIs
Publication statusPublished - 2021

Keywords

  • Age dependent pattern
  • Genetic epilepsy
  • MWS
  • ZEB2

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