{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T12:03:26Z","timestamp":1790424206013,"version":"4.1.0"},"reference-count":32,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2017,4,10]],"date-time":"2017-04-10T00:00:00Z","timestamp":1491782400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["PO1 HDO24448"],"award-info":[{"award-number":["PO1 HDO24448"]}],"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":["4T32GM007748\u201038"],"award-info":[{"award-number":["4T32GM007748\u201038"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007857","name":"Intellectual and Developmental Disabilities Research Center","doi-asserted-by":"publisher","award":["1U54HD079123\u201001A1"],"award-info":[{"award-number":["1U54HD079123\u201001A1"]}],"id":[{"id":"10.13039\/100007857","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2017,6]]},"abstract":"<jats:sec><jats:label\/><jats:p>Rett syndrome (RTT) is caused by <jats:italic>MECP2<\/jats:italic> mutations, resulting in various neurological symptoms. Prolonged corrected QT interval (QTc) is also reported and is a speculated cause of sudden death in RTT. The purpose of this study was to correlate QTc in RTT patients with age, clinical severity, and genotype. 100 RTT patients (98 females, 2 males) with <jats:italic>MECP2<\/jats:italic> mutations underwent baseline neurological evaluation (KKI\u2010RTT Severity Scale) and QTc measurement (standard 12 lead electrocardiogram) as part of our prospective natural history study. Mean QTc of the cohort was 422.6 msec, which did not exceed the normal values for age. 7\/100 patients (7%) had QTc prolongation (&gt;450 msec). There was a trend for increasing QTc with age and clinical severity (<jats:italic>P<\/jats:italic>\u2009=\u20090.09). No patients with R106C, R106W, R133C, R168*, R270*, R294*, R306C, R306H, and R306P mutations demonstrated QTc prolongation. There was a relatively high proportion of QTc prolongation in patients with R255* mutations (2\/8, 25%) and large deletions (1\/4, 25%). The overall presence of QTc prolongation did not correlate with mutation category (<jats:italic>P<\/jats:italic>\u2009=\u20090.52). Our findings demonstrate that in RTT, the prevalence of QTc prolongation is lower than previously reported. Hence, all RTT patients warrant baseline ECG; if QTc is prolonged, then cardiac followup is warranted. If initial QTc is normal, then annual ECGs, particularly in younger patients, may not be necessary. However, larger sample sizes are needed to solidify the association between QTc and age and clinical severity. The biological and clinical significance of mild QTc prolongation above the normative data remains undetermined.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.38191","type":"journal-article","created":{"date-parts":[[2017,4,10]],"date-time":"2017-04-10T13:12:42Z","timestamp":1491829962000},"page":"1495-1501","source":"Crossref","is-referenced-by-count":29,"title":["Evaluation of QTc in Rett syndrome: Correlation with age, severity, and genotype"],"prefix":"10.1002","volume":"173","author":[{"given":"Jane","family":"Crosson","sequence":"first","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7008-1879","authenticated-orcid":false,"given":"Siddharth","family":"Srivastava","sequence":"additional","affiliation":[{"name":"Department of Neurology Boston Children's Hospital Boston Massachusetts"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Genila M.","family":"Bibat","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics Kennedy Krieger Institute Baltimore Maryland"},{"name":"Department of Pediatrics Johns Hopkins School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Siddharth","family":"Gupta","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics Kennedy Krieger Institute Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aditi","family":"Kantipuly","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics Kennedy Krieger Institute Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Constance","family":"Smith\u2010Hicks","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics Kennedy Krieger Institute Baltimore Maryland"},{"name":"Department of Pediatrics Johns Hopkins School of Medicine Baltimore Maryland"},{"name":"Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott M.","family":"Myers","sequence":"additional","affiliation":[{"name":"Autism &amp; Developmental Institute Geisinger Health System Lewisburg Pennsylvania"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abanti","family":"Sanyal","sequence":"additional","affiliation":[{"name":"Johns Hopkins Biostatistics Center, Department of Biostatistics Johns Hopkins University Bloomberg School of Public Health Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gayane","family":"Yenokyan","sequence":"additional","affiliation":[{"name":"Johns Hopkins Biostatistics Center, Department of Biostatistics Johns Hopkins University Bloomberg School of Public Health Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joel","family":"Brenner","sequence":"additional","affiliation":[{"name":"Division of Pediatric Cardiology, Department of Pediatrics Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sakkubai R.","family":"Naidu","sequence":"additional","affiliation":[{"name":"Department of Neurogenetics Kennedy Krieger Institute Baltimore Maryland"},{"name":"Department of Pediatrics Johns Hopkins School of Medicine Baltimore Maryland"},{"name":"Department of Neurology Johns Hopkins University School of Medicine Baltimore Maryland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2017,4,10]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.2005.090290"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2007.12.030"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/13810"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jns.2007.01.007"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.71.1.63"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jcfm.2005.08.013"},{"key":"e_1_2_8_8_1","volume-title":"GeneReviews(\u00ae)","author":"Christodoulou J.","year":"1993"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/ejechocard\/jer256"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2010-1513"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1177\/08830738040190121001"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(85)80540-4"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.80.5.470"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-004-0701-x"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1177\/088307380101600512"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-2007-973480"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00246-005-0784-z"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.410140412"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320250506"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1242\/dmm.020131"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.56.11.1486"},{"issue":"1","key":"e_1_2_8_22_1","first-page":"71","article-title":"Rett syndrome: Analysis of deaths in the British survey","volume":"6","author":"Kerr A. 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