Genetic and forensic implications in epilepsy and cardiac arrhythmias: a case series

• Published in: International journal of legal medicine 2015-05, Vol.129 (3), p.495-504
• Main Authors: Partemi, Sara, Vidal, Monica Coll, Striano, Pasquale, Campuzano, Oscar, Allegue, Catarina, Pezzella, Marianna, Elia, Maurizio, Parisi, Pasquale, Belcastro, Vincenzo, Casellato, Susanna, Giordano, Lucio, Mastrangelo, Massimo, Pietrafusa, Nicola, Striano, Salvatore, Zara, Federico, Bianchi, Amedeo, Buti, Daniela, La Neve, Angela, Tassinari, Carlo Alberto, Oliva, Antonio, Brugada, Ramon
• Format: Article
• Language: English
• Subjects: Alleles; Arrhythmias, Cardiac - genetics; Arrhythmias, Cardiac - mortality; Autopsies; Brain research; Brugada Syndrome - genetics; Brugada Syndrome - mortality; Cardiac arrhythmia; Channelopathies - genetics; Channelopathies - mortality; Codon, Nonsense - genetics; Cohort Studies; Cross-Sectional Studies; Death, Sudden - epidemiology; Death, Sudden - etiology; Disease; DNA Mutational Analysis; Epilepsy; Epilepsy - genetics; Epilepsy - mortality; Forensic Genetics; Forensic Medicine; Genetic Carrier Screening; Genetic Testing; Genetic Variation - genetics; Heart; Hospitals; Humans; Incidence; Long QT Syndrome - genetics; Long QT Syndrome - mortality; Maternal & child health; Medical Law; Medicine; Medicine & Public Health; Mutation; Mutation, Missense - genetics; Neurology; Neurosciences; Original Article; Sequence Analysis, DNA
• ISSN: 0937-9827; 1437-1596
• DOI: 10.1007/s00414-014-1063-4

Epilepsy affects approximately 3 % of the world’s population, and sudden death is a significant cause of death in this population. Sudden unexpected death in epilepsy (SUDEP) accounts for up to 17 % of all these cases, which increases the rate of sudden death by 24-fold as compared to the general population. The underlying mechanisms are still not elucidated, but recent studies suggest the possibility that a common genetic channelopathy might contribute to both epilepsy and cardiac disease to increase the incidence of death via a lethal cardiac arrhythmia. We performed genetic testing in a large cohort of individuals with epilepsy and cardiac conduction disorders in order to identify genetic mutations that could play a role in the mechanism of sudden death. Putative pathogenic disease-causing mutations in genes encoding cardiac ion channel were detected in 24 % of unrelated individuals with epilepsy. Segregation analysis through genetic screening of the available family members and functional studies are crucial tasks to understand and to prove the possible pathogenicity of the variant, but in our cohort, only two families were available. Despite further research should be performed to clarify the mechanism of coexistence of both clinical conditions, genetic analysis, applied also in post-mortem setting, could be very useful to identify genetic factors that predispose epileptic patients to sudden death, helping to prevent sudden death in patients with epilepsy.