Sudden Cardiac Arrest Panel

Sudden cardiac arrest (SCA) is a disorder in which the sudden cessation of cardiac activity leads to hemodynamic collapse. SCA happens quickly with little warning. Rapid treatment with a defibrillator can be lifesaving. SCA contributes significantly to morbidity and mortality in the general population (Mozaffarian et al. 2015). Most SCA cases (70-80%) are attributed to coronary heart disease (CHD); 10-15% are associated with nonischemic cardiomyopathy disease; approximately 5% are caused by arrhythmic disorders with no heart structural defects (Chugh et al. 2008). Identification of genetic factors associated with SCA contributes to the diagnosis, risk stratification and prevention (Refaat et al. 2015).

Genetic studies in affected families have indicated that inherited cardiac disorders are associated with sudden cardiac arrest (Noseworthy et al. 2008). These disorders involve structural cardiac disease (hypertrophic cardiomyopathy, dilated cardiomyopathy, and arrhythmogenic cardiomyopathy) and arrhythmogenic syndromes without structural abnormalities (such as long QT syndrome and Brugada syndrome) (Bezzina et al. 2015). Sudden cardiac arrest is a group of heterogenic disorders and can be autosomal dominant (AD), autosomal recessive (AR), or both. The majority of cardiac-related genes in this panel are associated with autosomal dominant disorders. The CASQ2 gene is associated with autosomal recessive cardiac-related disorders. The DSC2, DSP, JUP, KCNE1, KCNQ1, LMNA, TNNI3, and TTN genes are associated with autosomal dominant and recessive disorders (OMIM; Human Gene Mutation Database). See individual gene test descriptions for information on molecular biology of gene products.

Pathogenic variants may be detected in 10~30% of cases, depending on clinical setting, family history and associated cardiac disorder phenotype (Hertz et al. 2015; McGorrian et al. 2013).

Gross deletions or duplications have been reported in CACNB2, CAV3, DES, DSP, GPD1L, KCNH2, KCNJ2, KCNQ1, RYR2 and SCN5A as individual cases (Human Gene Mutation Database).

This test is performed using Next-Gen sequencing with additional Sanger sequencing as necessary.

This panel typically provides 99.5% coverage of all coding exons of the genes plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define coverage as ≥20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).