Chapters authored
Short QT Syndrome: Update on Genetic Basis
Short QT syndrome (SQTS) is an extremely rare inherited arrhythmogenic entity. Nowadays, less than 200 families affected worldwide have been reported. This syndrome is characterized by the presence of a short QT interval leading to malignant ventricular tachyarrhythmias, syncope and sudden cardiac death. It is one of the most lethal heart diseases in children and young adults. Both incomplete penetrance and variable expressivity are hallmarks of this entity, making it difficult to diagnose and manage. Currently, rare variants in nine genes have been associated with SQTS (CACNA1C, CACNA2D1, CACNB2, KCNH2, KCNJ2, KCNQ1, SLC22A5, SLC4A3 and SCN5A). However, only pathogenic variants in four genes (KCNH2, KCNQ1, KCNJ2 and SLC4A3) have been found to definitively cause SQTS. The remaining genes lack a clear association with the disease, making clinical interpretation of the variants challenging. The diagnostic yield of genetic tests is currently less than 30%, leaving most families clinically diagnosed with SQTS without a conclusive genetic diagnosis. We reviewed and updated the main genetic features of SQTS, as well as recent evidence on increasingly targeted treatment.
Part of the book: Rare Diseases
Samples Used in Molecular Autopsy: An Update
Molecular autopsy makes it possible to identify the genetic alteration responsible for an inherited arrhythmogenic disease, main suspected cause of sudden death in cases that remain unexplained after a complete medico-legal autopsy. By using next-generation sequencing technology, a massive genetic study can be carried out that identifies a rare variant classified as potentially pathogenic in up to 25% of sudden death cases in the young population. To carry out a post-mortem genetic study, it is necessary to have samples in suitable conservation conditions. Our chapter focuses on the type of samples that are used today in massively parallel genetic analyses.
Part of the book: Unlocking the Mysteries of Death