Title | A Natural History Study of Timothy Syndrome. |
Publication Type | Journal Article |
Year of Publication | 2024 |
Authors | Timothy, KW, Bauer, R, Larkin, KA, Walsh, EP, Abrams, DJ, Corcia, CGonzalez, Valsamakis, A, Pitt, GS, Dick, IE, Golden, A |
Journal | medRxiv |
Date Published | 2024 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. |
DOI | 10.1101/2024.05.20.24307583 |
Alternate Journal | medRxiv |
PubMed ID | 38826393 |
PubMed Central ID | PMC11142284 |