{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T12:46:31Z","timestamp":1768567591310,"version":"3.49.0"},"posted":{"date-parts":[[2024,5,21]]},"group-title":"Genetic and Genomic Medicine","reference-count":44,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,5,21]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:p>\n                  Timothy syndrome (OMIM #601005) is a rare disease caused by variants in the gene\n                  <jats:italic>CACNA1C<\/jats:italic>\n                  . Timothy syndrome patients were first identified as having a cardiac presentation of Long QT and syndactyly of the fingers and\/or toes, and an identical variant in\n                  <jats:italic>CACNA1C<\/jats:italic>\n                  , Gly406Arg. However, since this original identification, more individuals harboring diverse variants in\n                  <jats:italic>CACNA1C<\/jats:italic>\n                  have been identified and have presented with various cardiac and extra-cardiac symptoms. Furthermore, it has remained underexplored whether individuals harboring canonical Gly406Arg variants in mutually exclusive exon 8A (Timothy syndrome 1) or exon 8 (Timothy syndrome 2) have additional symptoms. Here, we describe the first Natural History Study for Timothy syndrome, providing a thorough resource describing the current understanding of disease manifestation in Timothy syndrome patients. Parents of Timothy syndrome children were queried regarding a wide-ranging set of symptoms and features via a survey. Importantly, we find that in addition to cardiac concerns, Timothy syndrome patients commonly share extra-cardiac features including neurodevelopmental impairments, hypoglycemia, and respiratory problems. Our work expands the current understanding of the disorder to better inform the care of Timothy syndrome patients.\n                <\/jats:p>","DOI":"10.1101\/2024.05.20.24307583","type":"posted-content","created":{"date-parts":[[2024,5,22]],"date-time":"2024-05-22T00:15:32Z","timestamp":1716336932000},"source":"Crossref","is-referenced-by-count":0,"title":["A Natural History Study of Timothy Syndrome"],"prefix":"10.64898","author":[{"given":"Katherine W.","family":"Timothy","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rosemary","family":"Bauer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kerry A.","family":"Larkin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edward P.","family":"Walsh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dominic J.","family":"Abrams","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia Gonzalez","family":"Corcia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexandra","family":"Valsamakis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Geoffrey S.","family":"Pitt","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7253-6846","authenticated-orcid":false,"given":"Ivy E.","family":"Dick","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andy","family":"Golden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024052407150904000_2024.05.20.24307583v1.1","doi-asserted-by":"publisher","DOI":"10.1007\/s003920070059"},{"key":"2024052407150904000_2024.05.20.24307583v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymgme.2010.05.011"},{"key":"2024052407150904000_2024.05.20.24307583v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90358-5"},{"key":"2024052407150904000_2024.05.20.24307583v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/ng0196-17"},{"key":"2024052407150904000_2024.05.20.24307583v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90359-3"},{"key":"2024052407150904000_2024.05.20.24307583v1.6","first-page":"54","article-title":"[The heart-hand syndrome. 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