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

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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.

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Acknowledgments

This work was supported by the Cardiovascular Genetics Center, University of Girona, Spain, and by Telethon Foundation Italy, Grant GGP10186A. We wish also to thank the Collaborative Group on SUDEP of Italian League Against Epilepsy (LICE) for the support in sample collections.

Authors’ contribution

The study concept or design was made by SP, MCV, PS, AO, and RB. All authors draft/revise the manuscript. All the authors made the analysis of interpretation.

Conflict of interests

The authors declare that they have no competing interests.

Disclosure

All authors report no disclosure.

Author information

Authors and Affiliations

  1. Institute of Legal Medicine, School of Medicine, Catholic University, Rome, Italy

    Sara Partemi, Monica Coll Vidal & Antonio Oliva

  2. Cardiovascular Genetics Center, Institut d’Investigació Biomèdica Girona-IdIBGi, Universitat de Girona, Girona, Spain

    Sara Partemi, Monica Coll Vidal, Oscar Campuzano, Catarina Allegue & Ramon Brugada

  3. Pediatric Neurology and Muscular Diseases Unit, DINOGMI-Department of Neurosciences, Rehabilitation, Ophthalmology, Genetics, Maternal and Child Health, University of Genova, Genoa, Italy

    Pasquale Striano & Marianna Pezzella

  4. Oasi Institute for Research on Mental Retardation and Brain Aging (IRCCS), Troina, EN, Italy

    Maurizio Elia

  5. Child Neurology, Chair of Pediatrics, NESMOS Department, Faculty of Medicine and Psychology, Sapienza University, Rome, Italy

    Pasquale Parisi

  6. Neurology Unit, Department of Medicine, S. Anna Hospital, Como, Italy

    Vincenzo Belcastro

  7. Department of Child Neuropsychiatry, University of Sassari, Sassari, Italy

    Susanna Casellato

  8. Pediatric Neuropsychiatric Division, Spedali Civili, Brescia, Italy

    Lucio Giordano

  9. Pediatric Neurology Unit, V. Buzzi Hospital, A.O. ICP, Milan, Italy

    Massimo Mastrangelo

  10. Department of Neurological and Psychiatric Sciences, Section of 1st Neurologic Clinic, University of Bari, Bari, Italy

    Nicola Pietrafusa & Angela La Neve

  11. Epilepsy Center, Department of Neuroscience, Reproductive Science and Odontostomatology, Federico II University, Naples, Italy

    Salvatore Striano

  12. Laboratory of Neurogenetics, Department of Neuroscience, Institute G. Gaslini, Genoa, Italy

    Federico Zara

  13. Department of Neurology and Epilepsy Centre (A.B..), San Donato Hospital, Arezzo, Italy

    Amedeo Bianchi

  14. Pediatric Neurology Unit and Laboratories, Children’s Hospital A. Meyer—University of Florence, Florence, Italy

    Daniela Buti

  15. Department of Neurological Sciences, University of Bologna, Bologna, Italy

    Carlo Alberto Tassinari

Authors
  1. Sara Partemi
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  2. Monica Coll Vidal
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  3. Pasquale Striano
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  4. Oscar Campuzano
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  5. Catarina Allegue
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  6. Marianna Pezzella
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  7. Maurizio Elia
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  8. Pasquale Parisi
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  9. Vincenzo Belcastro
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  10. Susanna Casellato
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  11. Lucio Giordano
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  13. Nicola Pietrafusa
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  14. Salvatore Striano
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  15. Federico Zara
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  16. Amedeo Bianchi
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  17. Daniela Buti
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  18. Angela La Neve
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  19. Carlo Alberto Tassinari
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  20. Antonio Oliva
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  21. Ramon Brugada
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Corresponding author

Correspondence to Antonio Oliva.

Additional information

Sara Partemi and Monica Coll Vidal equally contributed to this study.

Antonio Oliva and Ramon Brugada are co-senior authors

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Partemi, S., Vidal, M.C., Striano, P. et al. Genetic and forensic implications in epilepsy and cardiac arrhythmias: a case series. Int J Legal Med 129, 495–504 (2015). https://doi.org/10.1007/s00414-014-1063-4

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  • DOI: https://doi.org/10.1007/s00414-014-1063-4

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