{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T03:40:38Z","timestamp":1773459638979,"version":"3.50.1"},"reference-count":62,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2002,5,30]],"date-time":"2002-05-30T00:00:00Z","timestamp":1022716800000},"content-version":"vor","delay-in-days":149,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Ment. Retard. Dev. Disabil. Res. Rev."],"published-print":{"date-parts":[[2002,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Prospects for definitive therapeutic intervention for Rett syndrome (RS) have been elevated by the discovery of mutations in the methyl\u2010CpG\u2010binding protein 2 gene (<jats:italic>MECP2<\/jats:italic>) in more than 80% of females meeting clinical criteria for this disorder. As such, a review of previous clinical trials, descriptions of the status of clinical management for the prominent medical problems of RS, and a preview of an ongoing clinical trial conducted jointly at the Baylor College of Medicine and the University of Alabama at Birmingham are presented. The conduct of controlled clinical trials requires adherence to diagnostic criteria for RS; stratification by age, stage, and presence of <jats:italic>MECP2<\/jats:italic> mutations; and use of clearly defined outcome measures. Previous clinical trials in RS have been conducted with L\u2010carnitine, the ketogenic diet, and the opiate antagonist, naltrexone. The L\u2010carnitine and naltrexone trials were double blind, placebo\u2010controlled and us ed the motor behavioral analysis described in this review. All failed to provide evidence of dramatic improvements in the clinical features of RS. Specific recommendations are presented for clinical management of growth failure, breathing irregularities, seizures, ambulation, scoliosis, gastrointestinal function, self abuse, and habilitation\/education although systematic evaluations of each in the context of RS have not been conducted. The only ongoing trial involves dietary supplementation with folate and betaine and is based on the finding that gene expression of some alleles of the <jats:italic>agouti<\/jats:italic> gene could be altered by dietary methyl supplementation. The availability of animal models expressing mutations in <jats:italic>MECP2<\/jats:italic> should enhance the evaluation of innovative therapies for RS. MRDD Research Reviews 2002;8:106\u2013111. \u00a9 2002 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/mrdd.10022","type":"journal-article","created":{"date-parts":[[2002,10,6]],"date-time":"2002-10-06T12:27:22Z","timestamp":1033907242000},"page":"106-111","source":"Crossref","is-referenced-by-count":22,"title":["Clinical trials and treatment prospects"],"prefix":"10.1002","volume":"8","author":[{"given":"Alan K.","family":"Percy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2002,5,30]]},"reference":[{"key":"e_1_2_1_2_1","doi-asserted-by":"publisher","DOI":"10.1007\/s100380070032"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/1096-8628(200022)97:2<147::AID-AJMG6>3.0.CO;2-O"},{"key":"e_1_2_1_5_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_1_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410230432"},{"key":"e_1_2_1_7_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.5.611"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-8749.1990.tb08118.x"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.9.1377"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0168-9525(00)89009-5"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004390000422"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/0024-3205(89)90620-6"},{"key":"e_1_2_1_13_1","first-page":"103","article-title":"Rett syndrome: habilitation and management reviewed","volume":"6","author":"Budden SS","year":"1997","journal-title":"Eur Child Adolesc Psychiatry"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1086\/316913"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.7.1119"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/85906"},{"key":"e_1_2_1_17_1","first-page":"261","article-title":"Are somatic cells inherently deficient in methylation metabolism? A proposed mechanism for DNA methylation loss, senescence and aging","volume":"57","author":"Cooney CA","year":"1993","journal-title":"Growth, Development, & Aging"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/10.9.941"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.16.2365"},{"key":"e_1_2_1_20_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389901400306"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1002\/mds.870050303"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410210410"},{"key":"e_1_2_1_23_1","first-page":"486","article-title":"Effect of naloxone on breathing, hand movements, electroencephalogram during wakefulness in patients in rett syndrome","volume":"26","author":"Glaze D","year":"1989","journal-title":"Ann Neurol"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0013-4694(97)00084-9"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1097\/01241398-199103000-00013"},{"key":"e_1_2_1_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/85899"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320250525"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410140412"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.1985.tb10993.x"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0387-7604(85)80048-6"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320250506"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.8.610"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0387-7604(12)80200-2"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.11.1486"},{"key":"e_1_2_1_35_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/9.9.1369"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00688098"},{"key":"e_1_2_1_37_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.91.2.445"},{"key":"e_1_2_1_38_1","doi-asserted-by":"publisher","DOI":"10.1002\/humu.3"},{"key":"e_1_2_1_39_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007632-199407001-00013"},{"key":"e_1_2_1_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0387-7604(85)80039-5"},{"key":"e_1_2_1_41_1","doi-asserted-by":"publisher","DOI":"10.1097\/00005176-199907000-00010"},{"key":"e_1_2_1_42_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389400900319"},{"key":"e_1_2_1_43_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.2.357"},{"key":"e_1_2_1_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.ejhg.5200600"},{"key":"e_1_2_1_45_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.8.608"},{"key":"e_1_2_1_46_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410350415"},{"key":"e_1_2_1_47_1","doi-asserted-by":"publisher","DOI":"10.1097\/00008480-200012000-00014"},{"key":"e_1_2_1_48_1","doi-asserted-by":"publisher","DOI":"10.1097\/00007611-199312000-00021"},{"key":"e_1_2_1_49_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1046461"},{"key":"e_1_2_1_50_1","first-page":"723","article-title":"\u00dcber ein eigenartiges hirnatrophisches Syndrom bei Hyperammonamie im Kindesalter","volume":"116","author":"Rett A","year":"1966","journal-title":"Wien Med Wochenschr"},{"key":"e_1_2_1_51_1","volume-title":"\u00dcber ein cerebral\u2010atrophisches Syndrom bei Hyperammonaemie","author":"Rett A","year":"1966"},{"key":"e_1_2_1_52_1","first-page":"633","article-title":"The pattern of growth failure in Rett syndrome","volume":"147","author":"Schultz RJ","year":"1993","journal-title":"Am J Dis Child"},{"key":"e_1_2_1_53_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307389801300205"},{"key":"e_1_2_1_54_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.63.9.1039"},{"key":"e_1_2_1_55_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1651-2227.2001.tb00252.x"},{"key":"e_1_2_1_56_1","doi-asserted-by":"publisher","DOI":"10.1007\/s007870050045"},{"key":"e_1_2_1_57_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2008-1071568"},{"key":"e_1_2_1_58_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0959-437X(00)00083-6"},{"key":"e_1_2_1_59_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.55.8.1188"},{"key":"e_1_2_1_60_1","doi-asserted-by":"publisher","DOI":"10.1086\/302690"},{"key":"e_1_2_1_61_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.38.4.224"},{"key":"e_1_2_1_62_1","doi-asserted-by":"publisher","DOI":"10.1096\/fasebj.12.11.949"},{"key":"e_1_2_1_63_1","doi-asserted-by":"publisher","DOI":"10.1136\/jmg.37.4.250"}],"container-title":["Mental Retardation and Developmental Disabilities Research Reviews"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fmrdd.10022","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/mrdd.10022","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,14]],"date-time":"2023-09-14T10:08:16Z","timestamp":1694686096000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/mrdd.10022"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,1]]},"references-count":62,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2002,1]]}},"alternative-id":["10.1002\/mrdd.10022"],"URL":"https:\/\/doi.org\/10.1002\/mrdd.10022","archive":["Portico"],"relation":{},"ISSN":["1080-4013","1098-2779"],"issn-type":[{"value":"1080-4013","type":"print"},{"value":"1098-2779","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,1]]}}}