{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,22]],"date-time":"2026-02-22T07:51:16Z","timestamp":1771746676126,"version":"3.50.1"},"reference-count":24,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2015,3,19]],"date-time":"2015-03-19T00:00:00Z","timestamp":1426723200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Epilepsia"],"published-print":{"date-parts":[[2015,4]]},"abstract":"Summary<\/jats:title>Objective<\/jats:title>Rett syndrome is an X\u2010linked dominant neurodevelopmental disorder caused by mutations in the MECP<\/jats:styled-content>2<\/jats:italic> gene, and characterized by cognitive and communicative regression, loss of hand use, and midline hand stereotypies. Epilepsy is a core symptom, but literature is controversial regarding genotype\u2013phenotype correlation. Analysis of data from a large cohort should overcome this shortcoming.<\/jats:p><\/jats:sec>Methods<\/jats:title>Data from the Rett Syndrome Networked Database on 1,248 female patients were included. Data on phenotypic and genotypic parameters, age of onset, severity of epilepsy, and type of seizures were collected. Statistical analysis was done using the IBM SPSS<\/jats:styled-content> Version 21 software, logistic regression, and Kaplan\u2010Meier survival curves.<\/jats:p><\/jats:sec>Results<\/jats:title>Epilepsy was present in 68.1% of the patients, with uncontrolled seizures in 32.6% of the patients with epilepsy. Mean age of onset of epilepsy was 4.68\u00a0\u00b1\u00a0(standard deviation) 3.5\u00a0years. Younger age of onset was correlated to severity of epilepsy (Spearman correlation r\u00a0=\u00a00.668, p\u00a0<\u00a00.01). Patients with late truncating deletions had lower prevalence of epilepsy. Compared to them, the p.R133C<\/jats:italic> mutation, associated with a milder Rett phenotype, increased the risk for epilepsy (odds ratio [OR<\/jats:styled-content>]\u00a02.46, confidence interval [CI<\/jats:styled-content>] 95% 1.3\u20134.66), but not for severe epilepsy. The p.R255X<\/jats:italic> mutation conferred an increased risk for epilepsy (OR<\/jats:styled-content>\u00a02.07, CI<\/jats:styled-content> 95% 1.2\u20133.59) as well as for severe epilepsy (OR<\/jats:styled-content> 3.4, CI<\/jats:styled-content> 95% 1.6\u20137.3). The p.T158M<\/jats:italic> and p.C306C<\/jats:italic> mutations relatively increased the risk for severe epilepsy (OR<\/jats:styled-content>\u00a03.09 and 2.69, CI<\/jats:styled-content> 95% 1.48\u20136.4 and 1.19\u20136.05, respectively), but not for epilepsy occurrence.<\/jats:p><\/jats:sec>Significance<\/jats:title>Various mutations in the MECP<\/jats:styled-content>2<\/jats:italic> gene have a different influence on epilepsy, unrelated to the severity of the general Rett phenotype. This might suggest a site\u2010specific effect of MeCp2 on epileptic pathways. Further investigation of these mechanisms should promote better understanding of epileptogenesis in Rett syndrome.<\/jats:p><\/jats:sec>","DOI":"10.1111\/epi.12941","type":"journal-article","created":{"date-parts":[[2015,3,19]],"date-time":"2015-03-19T10:50:06Z","timestamp":1426762206000},"page":"569-576","source":"Crossref","is-referenced-by-count":53,"title":["Epilepsy in Rett syndrome\u2014Lessons from the Rett networked database"],"prefix":"10.1111","volume":"56","author":[{"given":"Andreea","family":"Nissenkorn","sequence":"first","affiliation":[{"name":"Pediatric Neurology Unit and Rett National Center Edmond and Lily Safra Children's Hospital Sheba Medical Center Tel HaShomer Israel"},{"name":"Sackler School of Medicine Tel Aviv University Tel Aviv Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rachel S.","family":"Levy\u2010Drummer","sequence":"additional","affiliation":[{"name":"The Mina & Everard Goodman Faculty of Life Sciences Bar\u2010Ilan University Ramat\u2010Gan Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ori","family":"Bondi","sequence":"additional","affiliation":[{"name":"The Mina & Everard Goodman Faculty of Life Sciences Bar\u2010Ilan University Ramat\u2010Gan Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alessandra","family":"Renieri","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit Biotechnology Department University of Siena Siena Italy"},{"name":"Medical Genetics University Hospital of Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Laurent","family":"Villard","sequence":"additional","affiliation":[{"name":"Faculty of Medicine INSERM UMR_S910 Marseille France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Mari","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit Biotechnology Department University of Siena Siena Italy"},{"name":"Medical Genetics University Hospital of Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria A.","family":"Mencarelli","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit Biotechnology Department University of Siena Siena Italy"},{"name":"Medical Genetics University Hospital of Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caterina","family":"Lo Rizzo","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit Biotechnology Department University of Siena Siena Italy"},{"name":"Medical Genetics University Hospital of Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilaria","family":"Meloni","sequence":"additional","affiliation":[{"name":"Medical Genetics Unit Biotechnology Department University of Siena Siena Italy"},{"name":"Medical Genetics University Hospital of Siena Siena Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mercedes","family":"Pineda","sequence":"additional","affiliation":[{"name":"Neuropediatrics and Molecular Genetics Hospital Sant Joan de Deu Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Judith","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Neuropediatrics and Molecular Genetics Hospital Sant Joan de Deu Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angus","family":"Clarke","sequence":"additional","affiliation":[{"name":"Institute of Medical Genetics Cardiff University Cardiff United Kingdom"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nadia","family":"Bahi\u2010Buisson","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology Paris Descartes University Imaging Institute INSERM U781 Paris France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bosnjak Vlatka","family":"Mejaski","sequence":"additional","affiliation":[{"name":"Children`s Hospital Medical School University of Zagreb Zagreb Croatia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Milena","family":"Djuric","sequence":"additional","affiliation":[{"name":"Mother and Child Health Institute of Serbia \u201cDr Vukan Cupic\u201d University of Belgrade Belgrade Serbia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana","family":"Craiu","sequence":"additional","affiliation":[{"name":"Carol Davila University of Medicine Pediatric Neurology Clinic Al Obregia Hospital Bucharest Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexsandra","family":"Djukic","sequence":"additional","affiliation":[{"name":"Rett Syndrome Center Montefiore Medical Center Albert Einstein College of Medicine New York New York U.S.A"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giorgio","family":"Pini","sequence":"additional","affiliation":[{"name":"Tuscany Rett Center Versilia Hospital Lido di Camaiore Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne Marie","family":"Bisgaard","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics Rigshospitalet Copenhagen Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bela","family":"Melegh","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University Medical School Pecs Hungary"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aglaia","family":"Vignoli","sequence":"additional","affiliation":[{"name":"Neurology Unit Epilepsy Center University of Milan Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Silvia","family":"Russo","sequence":"additional","affiliation":[{"name":"Molecular Genetics Laboratory Italilan 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