{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,2]],"date-time":"2026-11-02T11:41:48Z","timestamp":1793619708404,"version":"4.5.0"},"reference-count":12,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2015,7,31]],"date-time":"2015-07-31T00:00:00Z","timestamp":1438300800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American J of Med Genetics Pt A"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:label\/><jats:p>Timothy syndrome (TS) is a rare genetic condition that associates long QT syndrome, structural heart defects, dysmorphic facial features, syndactyly, seizures, developmental delay, and autism. Timothy syndrome type 1 is caused by a recurrent de novo mutation (p.Gly406Arg) in exon 8A of the L\u2010type calcium channel gene <jats:italic>CACNA1C<\/jats:italic>. Timothy syndrome type 2 was originally reported to be associated with a more severe cardiac phenotype but without syndactyly. Timothy syndrome type 2 is caused by mutation in an alternatively spliced exon 8 of the <jats:italic>CACNA1C<\/jats:italic> gene. Other mutations in <jats:italic>CACNA1C<\/jats:italic> are also reported with long QT syndrome with and without syndromic features overlapping that described in Timothy syndrome. The purpose of this report is to describe the presentation, physical features and natural history of a 4\u2010year\u2010old girl with Timothy syndrome type 2 due to the recurrent p.Gly406Arg mutation in exon 8 of <jats:italic>CACNA1C<\/jats:italic>. She has similar facial features to Timothy syndrome type 1 without syndactyly. She is developmentally delayed without autism. She recently had her first episode of torsade de pointes associated with febrile illness and hypoglycemia. The findings in this case provide further information about the phenotype and natural history of <jats:italic>CACNA1C<\/jats:italic> exon 8 mutation and together with previously reported cases of Timothy syndrome question whether the clinical and molecular distinction between Timothy syndromes types 1 and 2 remains clinically useful. \u00a9 2015 Wiley Periodicals, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ajmg.a.37258","type":"journal-article","created":{"date-parts":[[2015,7,31]],"date-time":"2015-07-31T06:18:50Z","timestamp":1438323530000},"page":"2780-2785","source":"Crossref","is-referenced-by-count":29,"title":["Long QT syndrome with craniofacial, digital, and neurologic features: Is it useful to distinguish between timothy syndrome types 1 and 2?"],"prefix":"10.1002","volume":"167","author":[{"given":"Vinson","family":"Diep","sequence":"first","affiliation":[{"name":"University of Hawai'i John A. Burns School of Medicine Honolulu Hawaii"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurie H.","family":"Seaver","sequence":"additional","affiliation":[{"name":"Department of Pediatrics University of Hawaii', John A. Burns School of Medicine Honolulu Hawaii"},{"name":"Kapiolani Medical Specialists Honolulu Hawaii"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7,31]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2013.28.5.788"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1542\/peds.2012-2941"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34223"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/europace\/euu063"},{"key":"e_1_2_5_6_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.34355"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1471-4159.1996.67010037.x"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.36924"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/0735-1097(94)00318-K"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2004.09.011"},{"key":"e_1_2_5_11_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0502506102"},{"key":"e_1_2_5_12_1","volume-title":"Timothy Syndrome. 2006 Feb 15 [Updated 2011 Apr 21]","author":"Splawski I"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1159\/000016320"}],"container-title":["American Journal of Medical Genetics Part A"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.a.37258","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.a.37258","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,6]],"date-time":"2023-10-06T20:58:24Z","timestamp":1696625904000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.a.37258"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2015,7,31]]},"references-count":12,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2015,11]]}},"alternative-id":["10.1002\/ajmg.a.37258"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.a.37258","archive":["Portico"],"relation":{},"ISSN":["1552-4825","1552-4833"],"issn-type":[{"value":"1552-4825","type":"print"},{"value":"1552-4833","type":"electronic"}],"subject":[],"published":{"date-parts":[[2015,7,31]]}}}