SADS is defined as sudden death under the age of 40 years old in the absence of 
structural heart disease. Family screening studies are able to identify a cause 
in up to 50% of cases-most commonly long QT syndrome (LQTS), Brugada and early 
repolarization syndrome, and catecholaminergic polymorphic ventricular 
tachycardia (CPVT) using standard clinical screening investigations including 
pharmacological challenge testing. These diagnoses may be supported by genetic 
testing which can aid cascade screening and may help guide management. In the 
current era it is possible to undertake molecular autopsy provided suitable 
samples of DNA can be obtained from the proband. With the evolution of rapid 
sequencing techniques it is possible to sequence the whole exome for candidate 
genes. This major advance offers the opportunity to identify novel causes of 
lethal arrhythmia but also poses the challenge of managing the volume of data 
generated and evaluating variants of unknown significance (VUS). The emergence 
of induced pluripotent stem cell technology could enable evaluation of the 
electrophysiological relevance of specific ion channel mutations in the proband 
or their relatives and will potentially enable screening of idiopathic 
ventricular fibrillation survivors combining genetic and electrophysiological 
studies in derived myocytes. This also could facilitate the assessment of 
personalized preventative pharmacological therapies. This review will evaluate 
the current screening strategies in SADS families, the role of molecular autopsy 
and genetic testing and the potential applications of molecular and cellular 
diagnostic strategies on the horizon.