A Natural History Study of Timothy Syndrome.

TitleA Natural History Study of Timothy Syndrome.
Publication TypeJournal Article
Year of Publication2024
AuthorsTimothy, KW, Bauer, R, Larkin, KA, Walsh, EP, Abrams, DJ, Corcia, CGonzalez, Valsamakis, A, Pitt, GS, Dick, IE, Golden, A
JournalmedRxiv
Date Published2024 May 21
Abstract

Timothy syndrome (OMIM #601005) is a rare disease caused by variants in the gene CACNA1C . 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 CACNA1C , Gly406Arg. However, since this original identification, more individuals harboring diverse variants in CACNA1C 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.

DOI10.1101/2024.05.20.24307583
Alternate JournalmedRxiv
PubMed ID38826393
PubMed Central IDPMC11142284