Electroclinical features of MEF2C haploinsufficiency-related epilepsy: A multicenter European study
- Creators
- Raviglione F.
- Douzgou S.
- Scala M.
- Mingarelli A.
- D'Arrigo S.
- Freri E.
- Darra F.
- Giglio S.
- Bonaglia M. C.
- Pantaleoni C.
- Mastrangelo M.
- Epifanio R.
- Elia M.
- Saletti V.
- Morlino S.
- Vari M. S.
- De Liso P.
- Pavaine J.
- Spaccini L.
- Cattaneo E.
- Gardella E.
- Moller R. S.
- Marchese F.
- Colonna C.
- Gandioli C.
- Gobbi G.
- Ram D.
- Palumbo O.
- Carella M.
- Germano M.
- Tonduti D.
- De Angelis D.
- Caputo D.
- Bergonzini P.
- Novara F.
- Zuffardi O.
- Verrotti A.
- Orsini A.
- Bonuccelli A.
- De Muto M. C.
- Trivisano M.
- Vigevano F.
- Granata T.
- Bernardina B. D.
- Tranchina A.
- Striano P.
- Others:
- Raviglione, F.
- Douzgou, S.
- Scala, M.
- Mingarelli, A.
- D'Arrigo, S.
- Freri, E.
- Darra, F.
- Giglio, S.
- Bonaglia, M. C.
- Pantaleoni, C.
- Mastrangelo, M.
- Epifanio, R.
- Elia, M.
- Saletti, V.
- Morlino, S.
- Vari, M. S.
- De Liso, P.
- Pavaine, J.
- Spaccini, L.
- Cattaneo, E.
- Gardella, E.
- Moller, R. S.
- Marchese, F.
- Colonna, C.
- Gandioli, C.
- Gobbi, G.
- Ram, D.
- Palumbo, O.
- Carella, M.
- Germano, M.
- Tonduti, D.
- De Angelis, D.
- Caputo, D.
- Bergonzini, P.
- Novara, F.
- Zuffardi, O.
- Verrotti, A.
- Orsini, A.
- Bonuccelli, A.
- De Muto, M. C.
- Trivisano, M.
- Vigevano, F.
- Granata, T.
- Bernardina, B. D.
- Tranchina, A.
- Striano, P.
Description
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.
Additional details
- URL
- http://hdl.handle.net/11567/1083885
- URN
- urn:oai:iris.unige.it:11567/1083885
- Origin repository
- UNIGE