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.

Further delineation and long-term evolution of electroclinical phenotype in Mowat Wilson Syndrome. A longitudinal study in 40 individuals / 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. Grioni, I. 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. - In: EPILEPSY & BEHAVIOR. - ISSN 1525-5050. - 124(2021 Nov), pp. 108315.1-108315.11. [10.1016/j.yebeh.2021.108315]

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

E. Ricci
Primo
;
E. Finardi;F. Raviglione;A. Vignoli;M. Canevini;
2021

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.
Age dependent pattern; Genetic epilepsy; MWS; ZEB2;
Settore MED/39 - Neuropsichiatria Infantile
4-ott-2021
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/876989
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