{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T19:15:10Z","timestamp":1791918910689,"version":"4.3.4"},"reference-count":40,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2020,6,29]],"date-time":"2020-06-29T00:00:00Z","timestamp":1593388800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of Neurology"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:sec><jats:title>Objective<\/jats:title><jats:p>Rett syndrome, <jats:italic>CDKL5<\/jats:italic>\u2010deficiency disorder, <jats:italic>FOXG1<\/jats:italic> disorder, and <jats:italic>MECP2<\/jats:italic> duplication disorder are developmental encephalopathies with shared and distinct features. Although they are historically linked, no direct comparison has been performed. The first head\u2010to\u2010head comparison of clinical features in these conditions is presented.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Comprehensive clinical information was collected from 793 individuals enrolled in the Rett and Rett\u2010Related Disorders Natural History Study. Clinical features including clinical severity, regression, and seizures were cross\u2010sectionally compared between diagnoses to test the hypothesis that these are 4 distinct disorders.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Distinct patterns of clinical severity, seizure onset age, and regression were present. Individuals with <jats:italic>CDKL5<\/jats:italic>\u2010deficency disorder were the most severely affected and had the youngest age at seizure onset (2\u2009months), whereas children with <jats:italic>MECP2<\/jats:italic> duplication syndrome had the oldest median age at seizure onset (64\u2009months) and lowest severity scores. Rett syndrome and <jats:italic>FOGX1<\/jats:italic> were intermediate in both features. Smaller head circumference correlates with increased severity in all disorders and earlier age at seizure onset in <jats:italic>MECP2<\/jats:italic> duplication syndrome. Developmental regression occurred in all Rett syndrome participants (median = 18\u2009months) but only 23 to 34% of the other disorders. Seizure incidence prior to the baseline visit was highest for <jats:italic>CDKL5<\/jats:italic> deficiency disorder (96.2%) and lowest for Rett syndrome (47.5%). Other clinical features including seizure types and frequency differed among groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>Although these developmental encephalopathies share many clinical features, clear differences in severity, regression, and seizures warrant considering them as unique disorders. These results will aid in the development of disease\u2010specific severity scales, precise therapeutics, and future clinical trials. <jats:bold>ANN NEUROL 2020;88:396\u2013406.<\/jats:bold><\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.25797","type":"journal-article","created":{"date-parts":[[2020,5,30]],"date-time":"2020-05-30T14:08:15Z","timestamp":1590847695000},"page":"396-406","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Comparison of Core Features in Four Developmental Encephalopathies in the Rett Natural History Study"],"prefix":"10.1002","volume":"88","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9774-7706","authenticated-orcid":false,"given":"Clare","family":"Cutri\u2010French","sequence":"first","affiliation":[{"name":"Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dallas","family":"Armstrong","sequence":"additional","affiliation":[{"name":"Division of Child Neurology Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joni","family":"Saby","sequence":"additional","affiliation":[{"name":"Division of Radiology Research Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Casey","family":"Gorman","sequence":"additional","affiliation":[{"name":"Division of Child Neurology Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jane","family":"Lane","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Civitan International Research Center University of Alabama at Birmingham  Birmingham Alabama"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cary","family":"Fu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vanderbilt Kennedy Center Vanderbilt University Medical Center  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarika U.","family":"Peters","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vanderbilt Kennedy Center Vanderbilt University Medical Center  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alan","family":"Percy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Vanderbilt Kennedy Center Vanderbilt University Medical Center  Nashville Tennessee"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5628-5872","authenticated-orcid":false,"given":"Jeffrey L.","family":"Neul","sequence":"additional","affiliation":[{"name":"Division of Child Neurology Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3264-0902","authenticated-orcid":false,"given":"Eric D.","family":"Marsh","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine at the University of Pennsylvania  Philadelphia Pennsylvania"},{"name":"Division of Child Neurology Children's Hospital of Philadelphia  Philadelphia Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,29]]},"reference":[{"key":"e_1_2_9_2_1","unstructured":"SwaimanKF AshwalS FerrieroDM et al. 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