{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:15:50Z","timestamp":1790730950825,"version":"4.1.0"},"reference-count":20,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T00:00:00Z","timestamp":1750032000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of the Child Neurology Society"],"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Objective<\/jats:title>\n                    <jats:p>We aim to assess the clinical features of Rett syndrome (RTT) at registration into the National Institutes of Health\u2013sponsored natural history study (NHS) using the Clinical Severity Scale (CSS).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>The CSS was established in 2000 to assess characteristics of individuals with RTT and related disorders. We analyzed the CSS at enrollment into the NHS of all individuals with classic RTT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The CSS of 1258 individuals was used to examine three historical items (age at regression, age at onset of hand stereotypies, and head growth) and 10 clinical features at initial enrollment.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Among historical items, age at regression was most prominent after age 12 months with 8% regressing before this, hand stereotypies were most common after 18 months with 30% occurring before, and head growth was substantially lower overall. Hand use, ambulation, and communication skills were reduced in most individuals.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion and Conclusion<\/jats:title>\n                    <jats:p>\n                      These findings reflect core clinical criteria for classic RTT and mirror the top concerns registered independently by parents or caregivers. The CSS is an important analytic tool for the association of relative differences in clinical outcome with specific\n                      <jats:italic>MECP2<\/jats:italic>\n                      variant groups and has been important in establishing entrance criteria in RTT clinical trials. The range of age\u2010specific CSS features will continue to inform the RTT natural natural history\u00a0as well as provide stratification and selection in future clinical trials, especially those involving younger participants.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cns3.70017","type":"journal-article","created":{"date-parts":[[2025,6,16]],"date-time":"2025-06-16T05:44:46Z","timestamp":1750052686000},"page":"152-157","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Symptom Onset in Classic Rett Syndrome: Analysis of Initial Clinical Severity Scale Entries"],"prefix":"10.1002","volume":"3","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9873-5472","authenticated-orcid":false,"given":"Alan K.","family":"Percy","sequence":"first","affiliation":[{"name":"Department of Pediatrics (Neurology), Heersink School of Medicine University of Alabama at Birmingham Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeffrey L.","family":"Neul","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Neurology) Vanderbilt University Medical School and Vanderbilt University, Vanderbilt Kennedy Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amitha","family":"Ananth","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Neurology), Heersink School of Medicine University of Alabama at Birmingham Birmingham Alabama USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timothy A.","family":"Benke","sequence":"additional","affiliation":[{"name":"Department of Pediatrics (Neurology) Children's Hospital of Colorado\/University of Colorado School of Medicine Aurora Colorado USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric D.","family":"Marsh","sequence":"additional","affiliation":[{"name":"Perelman School of Medicine, Division of Neurology, Children's Hospital of Philadelphia University of Pennsylvania Philadelphia Pennsylvania USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,6,16]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/1531-8249(200005)47:5<670::AID-ANA20>3.0.CO;2-F"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000291011.54508.aa"},{"issue":"4","key":"e_1_2_9_4_1","first-page":"e46","article-title":"NNZ\u20102566: A Novel, Experimental Treatment for Rett Syndrome","volume":"85","author":"Glaze D. 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