0486: Postmortem genetic testing in a series of 36 young patients after sudden cardiac death

Abstract

The incidence of sudden cardiac death (SCD) increases with age in parallel with coronary’s diseases’ prevalence. In young persons and athletes, SCD occurs in half of the cases, in the setting of genetically transmitted disorders such as cardiomyopathies. Molecular testing performed after necropsy may help management of families but experience in this area appears very limited. The aim is to report our experience of post mortem molecular testing after SCD and necropsy. We studied 36 patients <40 years who died suddenly with a suspected diagnosis of cardiomyopathy, established either after autopsy or known before death, with 6 dilated cardiomyopathy (DCM), 12 hypertrophic (HCM), 2 HCM/DCM, 1 restrictive (CMR), 14 arrhythmogenic right ventricular cardiomyopathy (ARVC), 1 HMC and left ventricular noncompaction. Sanger sequencing was performed in most 4-5 frequent genes for a given phenotype. Fifteen mutations have been identified in sarcomeric (11 mutations) or desmosomal (3 mutations) or lamin (1 mutation) genes. The identification of these mutations had significant impact: assessing right diagnosis in a doubtful case (HCM without LVH), modifying the appropriate diagnosis in another case (HCM and not DCM), confirming a genetic disease even in the absence of affected relatives in the family, providing guidance for genetic counselling and predictive genetic testing in relatives in all situations. Technical, ethical and legal issues may however be encountered and will be discussed. This study is one of rare series of post-mortem molecular testing after SCD. Our findings suggest the feasibility, molecular efficiency and the clinical benefit of the approach in order to improve the management of families. Postmortem molecular testing must take its place in the strategy of family care after SCD, even if a cardiomyopathy is suspected at necropsy, since genetic findings provide additional information useful for the relatives.