A Natural History Study of Timothy Syndrome

• DOI: 10.1186/s13023-024-03445-x
• Publication Date: 2024-11-23T13:18:47Z
• Authors: Katherine W. Timothy; Rosemary Bauer; Kerry A. Larkin; Edward P. Walsh; Dominic J. Abrams; Cecilia Gonzalez ...; Alexandra Valsamakis; Geoffrey S. Pitt; Ivy E. Dick; Andy Golden
• Keywords: Syndactyly

Abstract Background Timothy syndrome (OMIM #601005) is a rare disease caused by variants in the gene CACNA1C . Initially, was characterized cardiac presentation of long QT and syndactyly fingers and/or toes, all associated with variant, Gly406Arg. However, subsequent identification diverse has expanded clinical spectrum, revealing various extra-cardiac manifestations. It remains underexplored whether individuals canonical Gly406Arg mutually exclusive exon 8A (Timothy 1) or 8 2) exhibit overlapping symptoms. Moreover, case reports have indicated that some may produce cardiac-selective form often referred to as non-syndromic type cardiac-only syndrome, however few follow up on these patients confirm selectivity phenotype over time. Methods A survey administered parents querying broad range symptoms features. Study participants were organized into 5 separate categories based genotype initial diagnosis, enabling comparison between groups which been described differentially literature. Results Our findings reveal commonly both features, neurodevelopmental impairments, hypoglycemia, respiratory issues being frequently reported. Notably, incidence features similar across patient categories, including those diagnosed 8, suggesting ‘non-syndromic’ classification be incomplete. Conclusions This study represents first Natural History offering comprehensive overview disease’s We demonstrate are prevalent groups, underscoring syndromic nature variants. While critical role arrhythmias well recognized, our indicate hypoglycemia dysfunction also pose significant life-threatening risks, emphasizing need for therapeutic management affected individuals.