{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,30]],"date-time":"2026-10-30T12:24:38Z","timestamp":1793363078512,"version":"4.5.0"},"reference-count":28,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T00:00:00Z","timestamp":1691712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Over the last 20 years, the understanding and natural history of Rett syndrome has advanced, but to date no cure has emerged, with multidisciplinary management being symptomatic and supportive. This study provides a comprehensive review of the clinical features, comorbidities and multidisciplinary management of a well-characterized cohort of females with classical Rett syndrome. We aim to improve awareness and understanding of Rett syndrome amongst pediatricians, pediatric subspecialists and allied health professionals to enable early diagnosis and a streamlined enrolment approach for future clinical trials. Rett syndrome, a complex X-linked condition, affecting mainly females, is due to pathogenic variants of the MECP2 gene in most affected individuals. The Rett syndrome Multidisciplinary Management clinic at The Children\u2019s Hospital at Westmead, Sydney, Australia, was established in 2000. This retrospective analysis of individuals who attended the clinic from 2000 to 2020 was performed to identify the incidence and predicted age of onset of Rett syndrome related comorbidities, disease progression and to review management principles. Data collected included age of Rett syndrome diagnosis, MECP2 genotype, clinical features and medical comorbidities, such as sleep disturbance, seizures, breathing irregularities, scoliosis, mobility, hand stereotypies, hand function, constipation, feeding ability, use of gastrostomy, communication skills, QTc prolongation, anthropometry, and bruxism. Analysis of 103 girls who fulfilled the clinical diagnostic criteria for classical Rett syndrome with a pathogenic variant of the MECP2 gene showed a median age of diagnosis of 3 years. The most frequent MECP2 variant was c.502 C&gt;T.<\/jats:p>","DOI":"10.3390\/genes14081607","type":"journal-article","created":{"date-parts":[[2023,8,11]],"date-time":"2023-08-11T10:20:16Z","timestamp":1691749216000},"page":"1607","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":30,"title":["Multidisciplinary Management of Rett Syndrome: Twenty Years\u2019 Experience"],"prefix":"10.3390","volume":"14","author":[{"given":"Sandra","family":"Vilvarajan","sequence":"first","affiliation":[{"name":"Faculty of Medicine, Sydney University, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0004-3938-6091","authenticated-orcid":false,"given":"Madeleine","family":"McDonald","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Sydney University, Sydney, NSW 2006, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lyndal","family":"Douglas","sequence":"additional","affiliation":[{"name":"Department of Clinical Genetics, Children\u2019s Hospital at Westmead, Sydney, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica","family":"Newham","sequence":"additional","affiliation":[{"name":"Department of Physiotherapy, Children\u2019s Hospital at Westmead, Sydney, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robyn","family":"Kirkland","sequence":"additional","affiliation":[{"name":"Department of Occupational Therapy, Children\u2019s Hospital at Westmead, Sydney, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gloria","family":"Tzannes","sequence":"additional","affiliation":[{"name":"Department of Speech Pathology, Children\u2019s Hospital at Westmead, Sydney, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Diane","family":"Tay","sequence":"additional","affiliation":[{"name":"Department of Dentistry, Children\u2019s Hospital at Westmead, Sydney, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8431-0641","authenticated-orcid":false,"given":"John","family":"Christodoulou","sequence":"additional","affiliation":[{"name":"Discipline of Child and Adolescent Health, The University of Sydney, Sydney, NSW 2006, Australia"},{"name":"Brain and Mitochondrial Research Group, Murdoch Children\u2019s Research Institute, Melbourne, VIC 3052, Australia"},{"name":"Department of Pediatrics, University of Melbourne, Melbourne, VIC 3052, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Susan","family":"Thompson","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Sydney University, Sydney, NSW 2006, Australia"},{"name":"Genetic Metabolic Disorders Service, Children\u2019s Hospital at Westmead, Sydney, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carolyn","family":"Ellaway","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, Sydney University, Sydney, NSW 2006, Australia"},{"name":"Discipline of Child and Adolescent Health, The University of Sydney, Sydney, NSW 2006, Australia"},{"name":"Genetic Metabolic Disorders Service, Children\u2019s Hospital at Westmead, Sydney, NSW 2145, Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,8,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1016\/j.jpeds.2005.10.037","article-title":"Rett syndrome in Australia: A review of the epidemiology","volume":"148","author":"Laurvick","year":"2006","journal-title":"J. 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