{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,12]],"date-time":"2026-03-12T20:20:35Z","timestamp":1773346835037,"version":"3.50.1"},"reference-count":15,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T00:00:00Z","timestamp":1694476800000},"content-version":"vor","delay-in-days":11,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["HD083181"],"award-info":[{"award-number":["HD083181"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54 HD061222"],"award-info":[{"award-number":["U54 HD061222"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["U54HD083211"],"award-info":[{"award-number":["U54HD083211"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Annals of the Child Neurology Society"],"published-print":{"date-parts":[[2023,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Objective<\/jats:title><jats:p>We aimed to determine the longitudinal distribution of hand function skills in individuals with classic Rett syndrome (RTT), an X\u2010linked dominant neurodevelopmental disorder, and correlate with <jats:italic>MECP2<\/jats:italic> variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We conducted a longitudinal study of 946 girls and young women with typical RTT seen between 2006 and 2021 in the US Natural History Study (NHS) featuring a structured clinical evaluation to assess the level of hand function skills. The specific focus of\u00a0this study was to assess longitudinal variation of hand skills from age 2 through age 18 years in relation to specific <jats:italic>MECP2<\/jats:italic> variant groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Following the initial regression period, hand function continues to decline across the age spectrum in individuals with RTT. Specific differences are noted with steeper declines in hand function among those with milder variants (Group A: R133C, R294X, R306C, and C\u2010terminal truncations) compared with groups composed of individuals with more severe variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>These temporal variations in hand use represent specific considerations that\u00a0could influence the design of clinical trials that test therapies aiming to ameliorate specific functional limitations in individuals with RTT. Furthermore, the distinct impact of specific <jats:italic>MECP2<\/jats:italic> variants on clinical severity, especially related to hand use, should be considered in such interventional trials.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cns3.20038","type":"journal-article","created":{"date-parts":[[2023,9,12]],"date-time":"2023-09-12T12:58:50Z","timestamp":1694523530000},"page":"228-238","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Distribution of hand function by age in individuals with Rett syndrome"],"prefix":"10.1002","volume":"1","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5628-5872","authenticated-orcid":false,"given":"Jeffrey L.","family":"Neul","sequence":"first","affiliation":[{"name":"Department of Pediatrics Vanderbilt University Medical School Nashville Tennessee USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tim A.","family":"Benke","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, School of Medicine, Children's Hospital Colorado University of Colorado  Aurora Colorado USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric D.","family":"Marsh","sequence":"additional","affiliation":[{"name":"Division of Child Neurology, Departments of Neurology and Pediatrics, Children's Hospital of Philadelphia University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jane B.","family":"Lane","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David N.","family":"Lieberman","sequence":"additional","affiliation":[{"name":"Department of Pediatric Neurology, Boston Children's Hospital Harvard University  Boston Massachusetts USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Steven A.","family":"Skinner","sequence":"additional","affiliation":[{"name":"Greenwood Genetic Center Greenwood South Carolina USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Daniel G.","family":"Glaze","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Baylor College of Medicine Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bernhard","family":"Suter","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Baylor College of Medicine Houston Texas USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter T.","family":"Heydemann","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Rush Medical Center  Chicago Illinois USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Arthur A.","family":"Beisang","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Gillette Specialty Healthcare  St. Paul Minnesota USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shannon M.","family":"Standridge","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Cincinnati Children's Hospital Cincinnati Ohio USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robin C. C.","family":"Ryther","sequence":"additional","affiliation":[{"name":"Department of Neurology, School of Medicine Washington University St. Louis Missouri USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Richard H.","family":"Haas","sequence":"additional","affiliation":[{"name":"Departments of Neurosciences and Pediatrics University of California San Diego San Diego California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lloyd J.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Biostatistics, School of Public Health University of Alabama at Birmingham Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Amitha","family":"Ananth","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9873-5472","authenticated-orcid":false,"given":"Alan K.","family":"Percy","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Alabama at Birmingham  Birmingham Alabama USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2023,9,12]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"issue":"37","key":"e_1_2_9_3_1","first-page":"723","article-title":"[On a unusual brain atrophy syndrome in hyperammonemia in childhood]","volume":"116","author":"Rett A","year":"1966","journal-title":"Wiener medizinische Wochenschrift (1946)"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410140412"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.22124"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1053\/ejpn.2002.0612"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/01.wnl.0000291011.54508.aa"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870050303"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmedgenet-2013-102113"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jpeds.2021.06.060"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0000000000007560"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2018.03.010"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.braindev.2018.08.008"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11689-022-09432-2"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3182377dd2"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-023-02398-1"}],"container-title":["Annals of the Child Neurology Society"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cns3.20038","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,20]],"date-time":"2025-08-20T05:16:40Z","timestamp":1755667000000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cns3.20038"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9]]},"references-count":15,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2023,9]]}},"alternative-id":["10.1002\/cns3.20038"],"URL":"https:\/\/doi.org\/10.1002\/cns3.20038","archive":["Portico"],"relation":{},"ISSN":["2831-3267","2831-3267"],"issn-type":[{"value":"2831-3267","type":"print"},{"value":"2831-3267","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9]]},"assertion":[{"value":"2023-05-26","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-07-14","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2023-09-12","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}