Year: 2023
Type: article
Study design: Observational Study
Abstract: OBJECTIVE: Epilepsy with eyelid myoclonia (EEM) spectrum is a generalized form of epilepsy characterized by eyelid myoclonia with or without absences, eye closure-induced seizures with electroencephalographic paroxysms, and photosensitivity. Based on the specific clinical features, age at onset, and familial occurrence, a genetic cause has been postulated. Pathogenic variants in CHD2, SYNGAP1, NEXMIF, RORB, and GABRA1 have been reported in individuals with photosensitivity and eyelid myoclonia, but whether other genes are also involved, or a single gene is uniquely linked with EEM, or its subtypes, is not yet known. We aimed to dissect the genetic etiology of EEM. METHODS: We studied a cohort of 105 individuals by using whole exome sequencing. Individuals were divided into two groups: EEM- (isolated EEM) and EEM+ (EEM accompanied by intellectual disability [ID] or any other neurodevelopmental/psychiatric disorder). RESULTS: We identified nine variants classified as pathogenic/likely pathogenic in the entire cohort (8.57%); among these, eight (five in CHD2, one in NEXMIF, one in SYNGAP1, and one in TRIM8) were found in the EEM+ subcohort (28.57%). Only one variant (IFIH1) was found in the EEM- subcohort (1.29%); however, because the phenotype of the proband did not fit with published data, additional evidence is needed before considering IFIH1 variants and EEM- an established association. Burden analysis did not identify any single burdened gene or gene set. SIGNIFICANCE: Our results suggest that for EEM, as for many other epilepsies, the identification of a genetic cause is more likely with comorbid ID and/or other neurodevelopmental disorders. Pathogenic variants were mostly found in CHD2, and the association of CHD2 with EEM+ can now be considered a reasonable gene-disease association. We provide further evidence to strengthen the association of EEM+ with NEXMIF and SYNGAP1. Possible new associations between EEM+ and TRIM8, and EEM- and IFIH1, are also reported. Although we provide robust evidence for gene variants associated with EEM+, the core genetic etiology of EEM- remains to be elucidated.
Source: Epilepsia
DOI: 10.1111/epi.17859
Authors: Antonietta Coppola, S. Krithika, Michele Iacomino, Dheeraj Bobbili, Simona Balestrini, Irene Bagnasco, Leonilda Bilo, Daniela Buti, Susanna Casellato, Claudia Cuccurullo, Edoardo Ferlazzo, Costin Leu, Lucio Giordano, Giuseppe Gobbi, Laura Hernandez‐Hernandez, Nick Lench, Helena Martins, Stefano Meletti, Tullio Messana, Vincenzo Nigro, Michele Pinelli, Tommaso Pippucci, Ravishankara Bellampalli, Barbara Salis, Vito Sofia, Pasquale Striano, Salvatore Striano, Laura Tassi, Aglaia Vignoli, Anna Elisabetta Vaudano, Maurizio Viri, Ingrid E. Scheffer, Patrick May, Federico Zara, Sanjay M. Sisodiya
Institutions: Federico II University Hospital, University of Naples Federico II, UCL Queen Square Institute of Neurology, University College London, Epilepsy Society, Anglia Ruskin University, Istituto Giannina Gaslini, Luxembourg Centre for Systems Biomedicine, Meyer Children's Hospital, University of Florence, Ospedale Martini, Azienda Ospedaliero Universitaria di Sassari, Magna Graecia University, Azienda ospedaliera "Bianchi-Melacrino-Morelli", Broad Institute, Cleveland Clinic, Stanley Center for Psychiatric Research, Cleveland Clinic Research, Massachusetts Institute of Technology, Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, Istituto delle Scienze Neurologiche di Bologna, Rutherford Appleton Laboratory, Research Complex at Harwell, University of Modena and Reggio Emilia, Azienda Ospedaliero-Universitaria di Modena, Telethon Institute Of Genetics And Medicine, ASST Fatebenefratelli Sacco, University of Catania, University of Genoa, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda, University of Milan, Azienda Ospedaliero Universitaria Maggiore della Carita, Royal Children's Hospital, The University of Melbourne, Florey Institute of Neuroscience and Mental Health, Murdoch Children's Research Institute, Austin Health
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
Estimated APC paid: $3,950
Awards: Treat-ION - Neue Therapien für neurologische Ionenkanal- und Transporterstörungen - Teilprojekt Register, Charakterisierung von Erkrankungs-assoziierten genetischen Regionen, Datenintegration und Clinical Decision Support System für die Präzisionstherapie, G3205968077, Treat-ION - Neue Therapien für neurologische Ionenkanal- und Transporterstörungen - Teilprojekt 3 Bioinformatische Identifikation und Charakterisierung
OpenAlex ID: W4389711754