Provocative Cases -> Teaching Case Reports D-PO01 - Featured Poster Session (ID 11) Poster

D-PO01-085 - The Failure Of Current Risk Stratification Guidelines In SCN5A Overlap Syndromes - A Family Case Report (ID 914)

 D. Lee: Nothing relevant to disclose.


Background: SCN5A variants are associated with diverse clinical phenotypes including cardiomyopathy, conduction system disease and ventricular arrhythmia.
Objective: We identified a novel SCN5A variant (F1594L) in a pedigree affected by sudden cardiac death (SCD). Clinical phenotype and co-segregation with genotype within the pedigree were characterized.
Methods: Clinical data was collected by retrospective chart review. ECG analysis was by two independent electrophysiologists blinded to patient identity and genotype.
Results: Two of the six patients with the SCN5A variant had documented VF. A third obligate carrier suffered SCD in their 60s. In the gene positive group, 2/6 patients had at least one ECG showing a QTc>460ms and none had an ECG with a QTc >500ms; 5/6 patients had ventricular ectopy of variable morphologies. No patients had AV block but there was variable aberrancy of AV conduction in 5/6 mutation positive individuals. No such abnormalities were seen in the 4 genotype negative individuals. No patients had a Brugada pattern ECG or evidence of cardiomyopathy on echocardiography. Only one patient met current criteria for primary prevention ICD implantation.
Conclusion: This malignant SCN5A variant co-segregated with an abnormal but highly variable phenotype consisting of predominantly no to mild QTc prolongation, AV conduction disease, multifocal PVCs and cardiac arrest. This case highlights the significant difficulty in risk stratification of subjects with SCN5A variants and overlapping phenotypes. Current risk stratification strategies are inadequate for the identification of high risk patients with SCN5A overlap syndromes.