Molecular diagnosis in juvenile Sudden Unexpected Deaths (SUDs) : preliminary results of an extended autopsy protocol in the Milan (Italy) area

The discovery of a wide set of fatal arrhythmogenic genetic mutations has led us to set up a dedicated protocol for the investigation of juvenile sudden unexpected death (SUD) cases. The proposed protocol was designed to focus special attention on the requirements of the relatives of the victims (particularly the “duty to recall” potentially ill members of the same family), on those of the inquiring Magistrates and on the researchers’. In a two-year period a total of 26 cases of SUD was examined at the Institute of Legal Medicine of the University of Milan. The age of the samples to be studied was set between 0 and 30. Genomic DNA extraction was performed in every case and molecular investigation with SSCP performed on KCNQ1, KCNH2, KCNE1, KCNE2 genes involved in Long QT Syndrome (LQTS), SCN5A gene involved in LQTS and Brugada Syndrome and hRYR2 gene involved in Catecholaminergic polymorphic ventricular tachycardia. Toxicological screening was performed in every case, while histological examinations were performed only upon Magistrate’s request. 5 out of 26 cases turned out to be positive for arrhythmogenic genetic mutations/polymorphisms: 3 mutations and 1 polymorphism in the KCNQ1 gene and 1 mutation in the KCNH2 gene. Interestingly, the toxicology screening was positive in 2 out of 4 cases for cocaine and/or morphine. These preliminary findings demonstrate the need to extend traditional autopsy to new genetic analyses in case of SUD, thus making of the autopsy an important tool for prevention.