National survey on the prevalence of single-gene aetiologies for genetic developmental and epileptic encephalopathies in Italy.

Autor:	Mei D; Neuroscience and Human Genetics Department, Meyer Children's Hospital IRCSS, Florence, Italy., Balestrini S; Neuroscience and Human Genetics Department, Meyer Children's Hospital IRCSS, Florence, Italy.; University of Florence, Florence, Italy., Parrini E; Neuroscience and Human Genetics Department, Meyer Children's Hospital IRCSS, Florence, Italy., Gambardella A; Dipartimento di Scienze Mediche e Chirurgiche, Università degli Studi Magna Graecia, Catanzaro, Italy., Annesi G; Institute for Biomedical Research and Innovation, National Research Council, Cosenza, Italy., De Giorgis V; Brain and Behavioral Sciences Department, University of Pavia, Pavia, Italy.; Childhood and Adolescence Epilepsy Center, Department of Child Neurology and Psychiatry, IRCCS Mondino Foundation, ERN EpiCARE Full Member, Pavia, Italy., Gana S; Neurogenetics Research Center, IRCCS Mondino Foundation, ERN EpiCARE Full Member, Pavia, Italy., Bassi MT; Laboratory of Genetics, Scientific Institute IRCCS Eugenio Medea, Bosisio Parini, Bosisio Parini, Italy., Zucca C; Clinical Neurophysiology Unit, Scientific Institute IRCCS E. Medea, Bosisio Parini, Italy., Elia M; Oasi Research Institute - IRCCS, Troina, Italy., Vetri L; Oasi Research Institute - IRCCS, Troina, Italy., Castellotti B; Unit of Medical Genetics and Neurogenetics, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy., Ragona F; Department of Pediatric Neuroscience, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy., Mastrangelo M; Department of Women/Child Health and Urological Sciences, Sapienza University of Rome, Rome, Italy.; Unit of Child Neurology and Psychiatry-Department of Neurosciences/Mental Health, Azienda Ospedaliero-Universitaria Policlinico Umberto I, Rome, Italy., Pisani F; Unit of Child Neurology and Psychiatry-Department of Neurosciences/Mental Health, Azienda Ospedaliero-Universitaria Policlinico Umberto I, Rome, Italy.; Department of Human Neuroscience, Sapienza University of Rome, Rome, Italy., d'Orsi G; Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy., Carella M; Fondazione IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, Foggia, Italy., Pruna D; Child Neurology and Epileptology, S. Michele Hospital, ASL Cagliari, Cagliari, Italy., Giglio S; Medical Genetics, R. Binaghi Hospital, ASL Cagliari, Cagliari, Italy., Marini C; Child neurology and psychiatric unit, Pediatric Hospital G. Salesi; AOU delle Marche, Ancona, Italy., Cesaroni E; Child neurology and psychiatric unit, Pediatric Hospital G. Salesi; AOU delle Marche, Ancona, Italy., Riva A; IRCCS Istituto Giannina Gaslini, Full Member of European Reference Network EpiCARE, Genova, Italy.; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy., Scala M; IRCCS Istituto Giannina Gaslini, Full Member of European Reference Network EpiCARE, Genova, Italy.; Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genova, Italy., Licchetta L; IRCCS Istituto delle Scienze Neurologiche di Bologna, IRCCS Istituto Delle Scienze Neurologiche di Bologna, Full member of the ERN EpiCARE, Bologna, Italy., Minardi R; IRCCS Istituto delle Scienze Neurologiche di Bologna, IRCCS Istituto Delle Scienze Neurologiche di Bologna, Full member of the ERN EpiCARE, Bologna, Italy., Contaldo I; Child Neurology and Psychiatric Unit, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy., Gambardella ML; Child Neurology and Psychiatric Unit, Fondazione Policlinico Universitario Agostino Gemelli, IRCCS, Rome, Italy., Cossu A; UOC Neuropsichiatria Infantile, Ospedale della Donna e del Bambino c/o Ospedale Civile Maggiore, AOUI Verona, Full member of ERN EpiCARE, Verona, Italy.; Department of Engineering for Innovation Medicine, University of Verona, Verona, Italy., Proietti J; UOC Neuropsichiatria Infantile, Ospedale della Donna e del Bambino c/o Ospedale Civile Maggiore, AOUI Verona, Full member of ERN EpiCARE, Verona, Italy.; Department of Engineering for Innovation Medicine, University of Verona, Verona, Italy., Cantalupo G; UOC Neuropsichiatria Infantile, Ospedale della Donna e del Bambino c/o Ospedale Civile Maggiore, AOUI Verona, Full member of ERN EpiCARE, Verona, Italy.; Department of Engineering for Innovation Medicine, University of Verona, Verona, Italy., Trivisano M; Neurology, Epilepsy and Movement Disorders Unit, Bambino Gesù Children's Hospital, IRCCS, Full Member of ERN EpiCARE, Rome, Italy., De Dominicis A; Neurology, Epilepsy and Movement Disorders Unit, Bambino Gesù Children's Hospital, IRCCS, Full Member of ERN EpiCARE, Rome, Italy., Specchio N; Neurology, Epilepsy and Movement Disorders Unit, Bambino Gesù Children's Hospital, IRCCS, Full Member of ERN EpiCARE, Rome, Italy., Tassi L; Claudio Munari Epilepsy Surgery Center, ASST Grande Ospedale Metropolitano Niguarda, Milan, Italy., Guerrini R; Neuroscience and Human Genetics Department, Meyer Children's Hospital IRCSS, Florence, Italy renzo.guerrini@meyer.it.; University of Florence, Florence, Italy.
Jazyk:	angličtina
Zdroj:	Journal of medical genetics [J Med Genet] 2024 Nov 28. Date of Electronic Publication: 2024 Nov 28.
DOI:	10.1136/jmg-2024-110328
Abstrakt:	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. Competing Interests: Competing interests: None declared. (© Author(s) (or their employer(s)) 2024. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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