{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,12]],"date-time":"2025-12-12T13:34:49Z","timestamp":1765546489278,"version":"build-2065373602"},"reference-count":16,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2019,8,23]],"date-time":"2019-08-23T00:00:00Z","timestamp":1566518400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Universit\u00e0 degli Studi di Perugia, Pediatrc Section","award":["PED-2019-01"],"award-info":[{"award-number":["PED-2019-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJERPH"],"abstract":"<jats:p>Rett syndrome (RTT) is a neurodevelopmental disorder with a genetic basis that is associated with the mutation of the X-linked methyl-CpG binding protein 2 (MECP2) gene in approximately 90% of patients. RTT is characterized by a brief period of normal development followed by loss of acquired skills and evolution towards impairment of brain and motor functions and multi-organ dysfunction. Originally, RTT was considered lethal in males as it has an X-linked dominant inheritance. However, although this syndrome has a higher incidence in females, rare cases are also documented in males. Here, we describe the case of an 11-year-old male patient with a microduplication MECP2 Xq28. Our patient is currently living, while his older brother with the same mutation died at the age of 9 years. We showed that the role of MECP2 as an epigenetic modulator and the X-chromosome inactivation pattern can explain the lethal clinical form of the older brother with the same microduplication MECP2 Xq28 presented by our patient who is still alive. Given the limited case history of RTT in males, further studies are needed to better characterize this syndrome in males and consequently improve the currently available therapeutic strategies.<\/jats:p>","DOI":"10.3390\/ijerph16173075","type":"journal-article","created":{"date-parts":[[2019,8,26]],"date-time":"2019-08-26T04:38:23Z","timestamp":1566794303000},"page":"3075","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Rett Syndrome in Males: The Different Clinical Course in Two Brothers with the Same Microduplication MECP2 Xq28"],"prefix":"10.3390","volume":"16","author":[{"given":"Maria Bernarda","family":"Pitzianti","sequence":"first","affiliation":[{"name":"Division of Child Neuropsychiatry, Department of Neuroscience, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Department of Child Neuropsychiatry, USL Umbria 2, 05100 Terni, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelo","family":"Santamaria Palombo","sequence":"additional","affiliation":[{"name":"Division of Child Neuropsychiatry, Department of Neuroscience, University of Rome Tor Vergata, 00133 Rome, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4103-2837","authenticated-orcid":false,"given":"Susanna","family":"Esposito","sequence":"additional","affiliation":[{"name":"Paediatric Clinic, Department of Surgical and Biomedical Sciences, Universit\u00e0 degli Studi di Perugia, 06129 Perugia, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Augusto","family":"Pasini","sequence":"additional","affiliation":[{"name":"Division of Child Neuropsychiatry, Department of Neuroscience, University of Rome Tor Vergata, 00133 Rome, Italy"},{"name":"Department of Child Neuropsychiatry, USL Umbria 2, 05100 Terni, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2019,8,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1377","DOI":"10.1093\/hmg\/9.9.1377","article-title":"MECP2 mutation account for most cases of typical forms of Rett Syndrome","volume":"9","author":"Bienvenu","year":"2000","journal-title":"Hum. Mol. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1038\/sj.ejhg.5201451","article-title":"Early onset seizures and Rett-like features associated with mutations in CDKL5","volume":"13","author":"Evans","year":"2005","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"59","DOI":"10.1136\/jmg.2009.067355","article-title":"Phenotypic variability in Rett syndrome associated with FOXG1 mutations in females","volume":"47","author":"Philippe","year":"2010","journal-title":"J. Med Genet."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1002\/ana.22124","article-title":"Rett syndrome: Revised diagnostic criteria and nomenclature","volume":"68","author":"Neul","year":"2010","journal-title":"Ann. 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Genet."}],"container-title":["International Journal of Environmental Research and Public Health"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/17\/3075\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T13:13:37Z","timestamp":1760188417000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1660-4601\/16\/17\/3075"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,8,23]]},"references-count":16,"journal-issue":{"issue":"17","published-online":{"date-parts":[[2019,9]]}},"alternative-id":["ijerph16173075"],"URL":"https:\/\/doi.org\/10.3390\/ijerph16173075","relation":{},"ISSN":["1660-4601"],"issn-type":[{"type":"electronic","value":"1660-4601"}],"subject":[],"published":{"date-parts":[[2019,8,23]]}}}