Electroclinical features of MEF2C haploinsufficiency-related epilepsy: A multicenter European study

Federico Raviglione*, Sofia Douzgou, Marcello Scala, Alessia Mingarelli, Stefano D'Arrigo, Elena Freri, Francesca Darra, Sabrina Giglio, Maria C Bonaglia, Chiara Pantaleoni, Massimo Mastrangelo, Roberta Epifanio, Maurizio Elia, Veronica Saletti, Silvia Morlino, Maria Stella Vari, Paola De Liso, Julija Pavaine, Luigina Spaccini, Elisa CattaneoElena Gardella, Rikke S Møller, Francesca Marchese, Clara Colonna, Claudia Gandioli, Giuseppe Gobbi, Dipak Ram, Orazio Palumbo, Massimo Carella, Michele Germano, Davide Tonduti, Diego De Angelis, Davide Caputo, Patrizia Bergonzini, Francesca Novara, Orsetta Zuffardi, Alberto Verrotti, Alessandro Orsini, Alice Bonuccelli, Maria Carmela De Muto, Marina Trivisano, Federico Vigevano, Tiziana Granata, Bernardo Dalla Bernardina, Antonia Tranchina, Pasquale Striano

*Corresponding author af dette arbejde

Publikation: Bidrag til tidsskriftArtikelForskningpeer review


PURPOSE: Epilepsy is a main manifestation in the autosomal dominant mental retardation syndrome caused by heterozygous variants in MEF2C. We aimed to delineate the electro-clinical features and refine the genotype-phenotype correlations in patients with MEF2C haploinsufficiency.

METHODS: We thoroughly investigated 25 patients with genetically confirmed MEF2C-syndrome across 12 different European Genetics and Epilepsy Centers, focusing on the epileptic phenotype. Clinical features (seizure types, onset, evolution, and response to therapy), EEG recordings during waking/sleep, and neuroimaging findings were analyzed. We also performed a detailed literature review using the terms "MEF2C", "seizures", and "epilepsy".

RESULTS: Epilepsy was diagnosed in 19 out of 25 (~80%) subjects, with age at onset <30 months. Ten individuals (40%) presented with febrile seizures and myoclonic seizures occurred in ~50% of patients. Epileptiform abnormalities were observed in 20/25 patients (80%) and hypoplasia/partial agenesis of the corpus callosum was detected in 12/25 patients (~50%). Nine patients harbored a 5q14.3 deletion encompassing MEF2C and at least one other gene. In 7 out of 10 patients with myoclonic seizures, MIR9-2 and LINC00461 were also deleted, whereas ADGRV1 was involved in 3/4 patients with spasms.

CONCLUSION: The epileptic phenotype of MEF2C-syndrome is variable. Febrile and myoclonic seizures are the most frequent, usually associated with a slowing of the background activity and irregular diffuse discharges of frontally dominant, symmetric or asymmetric, slow theta waves with interposed spike-and-waves complexes. The haploinsufficiency of ADGRV1, MIR9-2, and LINC00461 likely contributes to myoclonic seizures and spasms in patients with MEF2C syndrome.

Sider (fra-til)60-72
Antal sider13
Tidlig onlinedato30 mar. 2021
StatusUdgivet - maj 2021

Bibliografisk note

Copyright © 2021. Published by Elsevier Ltd.


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