Abstract 19763: Clinical Outcomes and Modes of Death in Timothy Syndrome in the Current Era: A Multi-Center International Study of a Rare Genetic Disorder
Introduction: Timothy syndrome (TS) is a rare genetic disorder of the L-type cardiac channel Cav1.2 encoded by CACNA1C. The seminal report in 2004 characterized TS as a multisystem disorder, consisting of QT prolongation, congenital heart defects, syndactyly, facial dysmorphism, developmental delay, and 50% mortality by the 3rd year of life. In the last decade additional data regarding outcomes of TS have been limited. The present study aims to investigate clinical outcomes, genetic mutations, and modes of death of TS in the current era.
Methods: A cohort of 17 patients with TS from 12 international tertiary care pediatric centers was included in this retrospective study. Data included demographics, clinical characteristics, electrocardiograms, genetic results, treatment strategies, and outcomes. Patients were classified as either early era or current era based on whether they were diagnosed pre- or post-2004.
Results: Three patients (#1 – 3) were classified as early era and 14 patients (#4 – 17) as current era. Mean follow-up period was 4.9 years (range 0 - 19 years). Amongst all patients, mean maximum QTc = 640 msec (range 500 – 976 msec). The canonical G406R mutation in exon 8 or 8a of CACNA1C was present in 8 (44%) patients. All patients were treated with beta blockers, with 11/14 (78%) current-era patients being treated with an implantable cardioverter defibrillator (ICD). Eleven (61%) total patients had an episode of aborted cardiac arrest, six associated with general anesthesia and two with hypoglycemia. There were four (22%) sudden deaths with one occurring in the early era and three in the current era.
Conclusions: In contrast to previously published data from the early era, TS mortality in patients diagnosed since 2004 is 27%. While increased numbers are needed for definitive results, the data suggests that ICD implantation may increase survival in TS patients, and there is a possible association between general anesthesia and hypoglycemia and sudden cardiac death.
Author Disclosures: K.A. Dufendach: None. K.W. Timothy: None. B. Blevins: None. A. Pflaumer: None. S. Etheridge: None. J. Perry: None. N.A. Blom: None. J. Temple: Consultant/Advisory Board; Modest; St. Jude Medical. D. Chowdhury: None. J. Skinner: None. C. Johnsrude: None. A. Bratincsak: None. J. Bos: None. M.J. Ackerman: Consultant/Advisory Board; Modest; Boston Scientific, Gilead Sciences, Medtronic, St. Jude Medical. Other; Significant; Transgenomic. M. Shah: None.
- © 2016 by American Heart Association, Inc.