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Molecular genetics has recently entered the field of sudden cardiac
death. The pioneering work of Mark Keating and his group has opened the way to the understanding of the role
of inherited ion channels abnormalities and their link to cardiac arrest.
In less than one decade three syndromes, based on genetically determined ion channel dysfunction, have been
described: The Long QT syndrome, Brugada syndrome and Lenegre-Lev syndrome.
This short review presents basic knowledge on the molecular properties of cardiac ion channels, on the
electrophysiological consequences of the mutations that interfere with their kinetic and the correlation with
clinical and electrocardiographic features.
Molecular genetics has completely changed the clinical approach to these syndromes, allowing to understand
their etiology, to modify their classification and demonstrating that some arrhythmogenic diseases considered as
completely independent disorders share defects on the same genes.
Application of molecular diagnosis to individuals affected by cardiac channelopaties has allowed clinicians to
“redraw” the epidemiology of the diseases and to modify the diagnostic algorithms. Patients previously
considered on clinical ground as “non affected” by a disease, have now been re-classified as silent gene carriers
of the inherited defect: this step represents a major improvement in the diagnostic capabilities and has a
profound impact on the patients and their families.
Understanding that mutations may not only “cause” a disease, but it may also predispose to electrical instability
is a recent concept that, if conclusively demonstrated, may change the risk stratification process not only in rare
genetic diseases, but also in multifactorial disorders.
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