Yu Liwei, Neves Raquel, Bos Martijn M, Tester David J, Sardana Mayank, Giudicessi John R, Ackerman Michael J
Department of Pediatric and Adolescent Medicine/Division of Pediatric Cardiology, Mayo Clinic, Rochester, MN, USA.
Department of Molecular Pharmacology & Experimental Therapeutics (Windland Smith Rice Sudden Death Genomics Laboratory), Mayo Clinic, Rochester, MN, USA.
J Cardiovasc Transl Res. 2025 Jun 17. doi: 10.1007/s12265-025-10638-7.
Genetic variants in CACNA1C are associated with several cardiac and neurologic conditions. We conducted a retrospective review of patients evaluated and treated who presented with a pathogenic (P), likely pathogenic (LP), or variant of uncertain significance (VUS) in CACNA1C. Among 4,774 patients, 49 had P, LP, or VUS variants (55% female; median age 15 years; mean QTc 481 ms). Of these, 22 had long QT syndrome type 8, 8 had Timothy syndrome, 2 had cardiac only Timothy syndrome, and 9 had no cardiac phenotype. Ten patients exhibited extracardiac findings. Thirty-one patients were treated with a beta-blocker, 21 patients had an implantable cardioverter-defibrillator (ICD). Nine patients were on intentional non-therapy. Six patients had at least 1 breakthrough cardiac event on follow-up. Overall, CACNA1C-positive patients present with diverse diagnoses and severity. Treatments vary by phenotype, however management with preventative measures only presents a reasonable option for some phenotype-negative, genotype-positive patients.
CACNA1C基因的遗传变异与多种心脏和神经疾病相关。我们对接受评估和治疗的患者进行了回顾性研究，这些患者的CACNA1C基因存在致病性（P）、可能致病性（LP）或意义未明的变异（VUS）。在4774例患者中，49例存在P、LP或VUS变异（女性占55%；中位年龄15岁；平均QTc为481毫秒）。其中，22例患有8型长QT综合征，8例患有蒂莫西综合征，2例仅患有心脏型蒂莫西综合征，9例无心脏表型。10例患者有心脏外表现。31例患者接受了β受体阻滞剂治疗，21例患者植入了植入式心律转复除颤器（ICD）。9例患者接受了非治疗。6例患者在随访期间至少发生1次心脏突破性事件。总体而言，CACNA1C阳性患者的诊断和严重程度各不相同。治疗因表型而异，然而，对于一些表型阴性、基因型阳性的患者，仅采取预防措施进行管理是一种合理的选择。
