Evaluation of CACNA1C-Positive Patients Evaluated in a Tertiary Genetic Heart Rhythm Clinic

Area of Science:

• Genetics
• Cardiology
• Neurology

Background:

• Genetic variants in CACNA1C are associated with cardiac and neurological disorders.
• CACNA1C gene mutations can lead to conditions like long QT syndrome and Timothy syndrome.

Purpose of the Study:

• To review patients with pathogenic, likely pathogenic, or variant of uncertain significance (VUS) CACNA1C variants.
• To understand the clinical presentation, management, and outcomes of individuals with CACNA1C variants.

Main Methods:

• Retrospective review of 4,774 patients.
• Analysis of patients with pathogenic, likely pathogenic, or VUS variants in CACNA1C.
• Evaluation of clinical phenotypes, treatments, and cardiac events.

Main Results:

• 49 patients had pathogenic, likely pathogenic, or VUS CACNA1C variants.
• Diagnoses included long QT syndrome type 8, Timothy syndrome, and extracardiac findings.
• Treatments included beta-blockers, implantable cardioverter-defibrillators (ICDs), and intentional non-therapy.

Conclusions:

• CACNA1C variants present with diverse clinical phenotypes and severity.
• Treatment approaches are phenotype-dependent.
• Preventative management may be appropriate for genotype-positive, phenotype-negative patients.