{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:46:07Z","timestamp":1776919567403,"version":"3.51.2"},"reference-count":17,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T00:00:00Z","timestamp":1776902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurol."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      Rett syndrome (RTT) is a rare neurodevelopmental disorder primarily caused by pathogenic variants in the MECP2 gene. Trofinetide (Daybue) became the first FDA-approved medication for RTT in March 2023. This study evaluates the real-world effectiveness and side effect profile of Trofinetide in 55 individuals (50 females, 5 males) with RTT or\n                      <jats:italic>MECP2<\/jats:italic>\n                      -related neurodevelopmental disorders over a 12-month period.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Data was collected through clinic assessments and caregiver reports.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Results demonstrated that 75.9% of individuals experienced some improvement in RTT symptoms by caregiver report, particularly in engagement, communication, and motor skills. The side effect profile was better than the phase 3 trials with only 48.1% reporting diarrhea and 16.7% experiencing vomiting.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Overall, the findings support the effectiveness of trofinetide in the RTT population and suggests potential effectiveness in the broader MECP2 population including males and those with atypical presentations. The data highlights the need for further work to determine long-term benefits in the full spectrum of MECP2 related disorders. Finally, the study highlights the importance of titration, individualized dosing and side effect management to improve retention and outcomes.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fneur.2026.1776146","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T04:21:13Z","timestamp":1776918073000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical experience using trofinetide in Rett syndrome and related MECP2 diagnosis at the children\u2019s hospital of Philadelphia post approval"],"prefix":"10.3389","volume":"17","author":[{"given":"Erin O\u2019Connor","family":"Prange","sequence":"first","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia","place":["Philadelphia, PA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis","family":"Fleysh","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia","place":["Philadelphia, PA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keerthana","family":"Reddy","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia","place":["Philadelphia, PA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Holly","family":"Dubbs","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia","place":["Philadelphia, PA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric D.","family":"Marsh","sequence":"additional","affiliation":[{"name":"Division of Neurology, Children\u2019s Hospital of Philadelphia","place":["Philadelphia, PA, United States"]},{"name":"Departments of Neurology and Pediatrics, University of Pennsylvania Perelman School of Medicine","place":["Philadelphia, PA, United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","first-page":"84","DOI":"10.1038\/s41572-024-00568-0","article-title":"Rett syndrome","volume":"10","author":"Gold","year":"2024","journal-title":"Nat Rev Dis Primers"},{"key":"ref2","doi-asserted-by":"publisher","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 Neurol"},{"key":"ref3","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1002\/ajmg.b.32707","article-title":"The array of clinical phenotypes of males with mutations in methyl-CpG binding protein 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of Rett syndrome: long-term safety and efficacy results of the 32-month, open-label LILAC-2 study","volume":"5","author":"Percy","year":"2024","journal-title":"Med"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"407","DOI":"10.1111\/dmcn.16482","article-title":"Real-world benefits and tolerability of trofinetide for the treatment of Rett syndrome: the LOTUS study","volume":"68","author":"Cosand","year":"2026","journal-title":"Dev Med Child Neurol"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"1743","DOI":"10.1177\/0883073815579707","article-title":"Improving treatment trial outcomes for Rett syndrome: the development of Rett-specific anchors for the clinical global impression scale","volume":"30","author":"Neul","year":"2015","journal-title":"J Child Neurol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"237","DOI":"10.1352\/1944-7558-128.3.237","article-title":"Rett syndrome behaviour questionnaire in children and adults with Rett syndrome: psychometric characterization and revised factor structure","volume":"128","author":"Oberman","year":"2023","journal-title":"Am J Intellect Dev Disabil"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"33","DOI":"10.1186\/s11689-023-09502-z","article-title":"Top caregiver concerns in Rett syndrome and related disorders: data from the US natural history study","volume":"15","author":"Neul","year":"2023","journal-title":"J Neurodev Disord"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"3609","DOI":"10.1007\/s11136-025-04048-0","article-title":"Parent\/caregiver perspectives of meaningful improvement in functional domains for people with CDKL5 deficiency disorder: a mixed-methods study","volume":"34","author":"Keeley","year":"2025","journal-title":"Qual Life Res"},{"key":"ref16","first-page":"740","volume-title":"Neurophysiology of Rett SyndromeJ Child Neurol","year":"2005"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"37","DOI":"10.1016\/j.pediatrneurol.2017.07.002","article-title":"A double-blind, randomized, placebo-controlled clinical study of trofinetide in the treatment of Rett syndrome","volume":"76","author":"Glaze","year":"2017","journal-title":"Pediatr Neurol"}],"container-title":["Frontiers in 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