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Identification of a SCN5A Genetic Variant Associated With Type 1 Brugada Syndrome (BrS) in a Family
Jack Jnani1, Dorota Gruber2, Tafadzwa Mtisi3
1Internal Medicine, North Shore University Hospital, Manhasset, USA.
Insights
Brugada pattern, a genetic disorder, increases sudden cardiac death risk. A SCN5A gene variant, initially uncertain, was reclassified as pathogenic due to family history and clinical context.
Area of Science:
- Cardiology
- Genetics
- Molecular Biology
Background:
- Brugada pattern is an EKG finding linked to genetic disorders and increased risk of sudden cardiac death.
- SCN5A gene mutations, encoding cardiac sodium channels, are associated with Brugada syndrome (BrS).
Observation:
- A patient presented with spontaneous type 1 Brugada pattern on routine EKG.
- Electrophysiological testing provoked ventricular tachycardia, leading to implantable cardioverter defibrillator placement.
- Family history included sudden cardiac death, syncope, and diagnosed BrS.
Findings:
- Genetic testing identified a SCN5A variant of uncertain significance (VUS) in the patient and six relatives.
- The VUS, in conjunction with clinical presentation and family segregation, supports reclassification to pathogenic.
- This highlights the importance of genetic analysis in diagnosing Brugada syndrome.
Implications:
- Reclassifying the SCN5A VUS as pathogenic aids in diagnosing BrS in affected families.
- This case underscores the clinical utility of genetic testing and family history in identifying arrhythmia risks.
- Understanding SCN5A variants is crucial for risk stratification and management of patients with Brugada pattern.
Abstract:
The Brugada pattern is associated with a genetic disorder characterized by ST-segment elevation in the right precordial leads on electrocardiogram (EKG) in the absence of structural heart disease. Patients with the Brugada pattern have an increased risk for ventricular tachyarrhythmia and sudden cardiac death. Loss-of-function mutations in the SCN5A gene which encodes the alpha subunit of the cardiac sodium channel have been associated with Brugada syndrome (BrS). We report a case of a patient who was found to have a spontaneous type 1 Brugada pattern on a routine EKG done prior to travel. He underwent electrophysiological testing (EPS) which provoked ventricular tachycardia and underwent implantable cardioverter defibrillator (ICD) placement. His family history revealed a history of sudden cardiac death, abnormal EKG, syncope, dilated cardiomyopathy, and BrS. Genetic testing revealed a variant of uncertain significance (VUS) in the SCN5A gene in the proband and six of his relatives. The SCN5A VUS in this clinical context and segregation with the disease in his family supports its reclassification to pathogenic.
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