title: Genetic and forensic implications in epilepsy and cardiac arrhythmias: a case series.
abstract: 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.
authors.affiliation: Institute of Legal Medicine, School of Medicine, Catholic University, Rome, Italy.
authors.forename: Sara
authors.initials: S
authors.lastname: Partemi
authors.forename: Monica Coll
authors.initials: MC
authors.lastname: Vidal
authors.forename: Pasquale
authors.initials: P
authors.lastname: Striano
authors.forename: Oscar
authors.initials: O
authors.lastname: Campuzano
authors.forename: Catarina
authors.initials: C
authors.lastname: Allegue
authors.forename: Marianna
authors.initials: M
authors.lastname: Pezzella
authors.forename: Maurizio
authors.initials: M
authors.lastname: Elia
authors.forename: Pasquale
authors.initials: P
authors.lastname: Parisi
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Belcastro
authors.forename: Susanna
authors.initials: S
authors.lastname: Casellato
authors.forename: Lucio
authors.initials: L
authors.lastname: Giordano
authors.forename: Massimo
authors.initials: M
authors.lastname: Mastrangelo
authors.forename: Nicola
authors.initials: N
authors.lastname: Pietrafusa
authors.forename: Salvatore
authors.initials: S
authors.lastname: Striano
authors.forename: Federico
authors.initials: F
authors.lastname: Zara
authors.forename: Amedeo
authors.initials: A
authors.lastname: Bianchi
authors.forename: Daniela
authors.initials: D
authors.lastname: Buti
authors.forename: Angela
authors.initials: A
authors.lastname: La Neve
authors.forename: Carlo Alberto
authors.initials: CA
authors.lastname: Tassinari
authors.forename: Antonio
authors.initials: A
authors.lastname: Oliva
authors.forename: Ramon
authors.initials: R
authors.lastname: Brugada
mesh_terms: D000483:Alleles; D001145:Arrhythmias, Cardiac / Q000235:genetics* / Q000401:mortality*; D053840:Brugada Syndrome / Q000235:genetics / Q000401:mortality; D053447:Channelopathies / Q000235:genetics / Q000401:mortality; D018389:Codon, Nonsense / Q000235:genetics; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D004252:DNA Mutational Analysis; D003645:Death, Sudden / Q000453:epidemiology* / Q000209:etiology*; D004827:Epilepsy / Q000235:genetics* / Q000401:mortality*; D053803:Forensic Genetics; D006580:Genetic Carrier Screening; D005820:Genetic Testing; D014644:Genetic Variation / Q000235:genetics; D006801:Humans; D015994:Incidence; D008133:Long QT Syndrome / Q000235:genetics / Q000401:mortality; D020125:Mutation, Missense / Q000235:genetics; D017422:Sequence Analysis, DNA
chemical_list: D018389:Codon, Nonsense