National survey on the prevalence of single-gene aetiologies for genetic developmental and epileptic encephalopathies in Italy
Year: 2024
Type: article
Study design: Observational Study
Abstract: Background We aimed to estimate real-world evidence of the prevalence rate of genetic developmental and epileptic encephalopathies (DEEs) in the Italian population over a 11-year period. Methods Fifteen paediatric and adult tertiary Italian epilepsy centres participated in a survey related to 98 genes included in the molecular diagnostic workflows of most centres. We included patients with a clinical diagnosis of DEE, caused by a pathogenic or likely pathogenic variant in one of the selected genes, with a molecular diagnosis established between 2012 and 2022. These data were used as a proxy to estimate the prevalence rate of DEEs. Results We included 1568 unique patients and found a mean incidence proportion of 2.6 patients for 100.000 inhabitants (SD=1.13) with consistent values across most Italian regions. The number of molecular diagnoses showed a continuing positive trend, resulting in more than a 10-fold increase between 2012 and 2022. The mean age at molecular diagnosis was 11.2 years (range 0–75). Pathogenic or likely pathogenic variants in genes with an autosomal dominant inheritance pattern occurred in 77% (n=1207) patients; 17% (n=271) in X-linked genes and 6% (n=90) in genes with autosomal recessive inheritance. The most frequently reported genes in the survey were SCN1A (16%), followed by KCNQ2 (5.6%) and SCN2A (5%). Conclusion Our study provides a large dataset of patients with monogenic DEE, from a European country. This is essential for informing decision-makers in drug development on the appropriateness of initiatives aimed at developing precision medicine therapies and is instrumental in implementing disease-specific registries and natural history studies.
Source: Journal of Medical Genetics
Authors: Davide Mei, Simona Balestrini, Elena Parrini, Antonio Gambardella, Grazia Annesi, Valentina De Giorgis, Simone Gana, Maria Teresa Bassi, Claudio Zucca, Maurizio Elia, Luigi Vetri, Barbara Castellotti, Francesca Ragona, Mario Mastrangelo, Francesco Pisani, Giuseppe d'Orsi, Massimo Carella, Dario Pruna, Sabrina Giglio, Carla Marini, Elisabetta Cesaroni, Antonella Riva, Marcello Scala, Laura Licchetta, Raffaella Minardi, Ilaria Contaldo, Maria Luigia Gambardella, Alberto Cossu, Jacopo Proietti, Gaetano Cantalupo, LICE Collaborative Group, Marina Trivisano, Angela De Dominicis, Nicola Specchio, Laura Tassi, Renzo Guerrini
Institutions: Meyer Children's Hospital, University of Florence, Magna Graecia University, Institute for Biomedical Research and Innovation, National Research Council, University of Pavia, Fondazione Istituto Neurologico Nazionale Casimiro Mondino, IRCCS Eugenio Medea, I.R.C.C.S. Oasi Maria SS, Fondazione IRCCS Istituto Neurologico Carlo Besta, Policlinico Umberto I, Sapienza University of Rome, Casa Sollievo della Sofferenza, Azienda Ospedaliero-Universitaria delle Marche, Fondazione Ospedale Salesi, Istituto Giannina Gaslini, University of Genoa, Istituto delle Scienze Neurologiche di Bologna, Agostino Gemelli University Polyclinic, Istituti di Ricovero e Cura a Carattere Scientifico, University of Verona, Azienda Ospedaliera Universitaria Integrata Verona, Bambino Gesù Children's Hospital, Azienda Socio Sanitaria Territoriale Grande Ospedale Metropolitano Niguarda
Language: English
Subfield: Psychiatry and Mental health
Field: Medicine
Domain: Health Sciences
Open Access status: hybrid
OpenAlex ID: W4404867022