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Heart rate and conductivity disorders in juvenile myoclonic epilepsy: genetic predictors

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General practitioners, therapists, and cardiologists do not have formal education (training) regarding cerebrocardial syndrome, primarily heart rhythm and conduction disorders in epilepsy and sudden unexpected death in epilepsy (SUDEP), as well as the potential arrhythmogenic effect of antiepileptic drugs. This lecture presents important elements of knowledge about the genetic predictors of cerebrocardial syndrome and SUDEP in juvenile myoclonic epilepsy, which is the most common form of genetic generalized epilepsy.

About the Authors

N. A. Shnayder
Bekhterev National Medical Research Centre for Psychiatry and Neurology; Krasnoyarsk State Medical University
Russian Federation

Natalia A. Shnayder – Dr. Med. Sc., Professor, Leading Researcher, Department of Personalized Psychiatry and Neurology; Leading Researcher, Center of Collective Usage “Molecular and Cellular Technologies”

ResearcherID: M-7084-2014; RSCI SPIN-code: 1952-3043

3 Bekhterev Str., Saint Petersburg 192019

1 Partizan Zheleznyak Str., Krasnoyarsk Region, Krasnoyarsk 660022

M. M. Petrova
Krasnoyarsk State Medical University
Russian Federation

Marina M. Petrova – Dr. Med. Sc., Professor, Head of the Department of Outpatient Therapy and General Practice with the Course of Postgraduate Education

Scopus Author ID: 23987271200; ResearcherID: L-5623-2014; RSCI SPIN-code: 5563-1009

1 Partizan Zheleznyak Str., Krasnoyarsk Region, Krasnoyarsk 660022

K. V. Petrov
Krasnoyarsk State Medical University
Russian Federation

Kirill V. Petrov – Resident of the Department of Neurological Diseases with the Course of Postgraduate Education

RSCI SPIN-code: 5830-0594

1 Partizan Zheleznyak Str., Krasnoyarsk Region, Krasnoyarsk 660022

D. V. Dmitrenko
Krasnoyarsk State Medical University
Russian Federation

Diana V. Dmitrenko – Dr. Med. Sc., Professor, Head of the Department of Medical Genetics and Clinical Neurophysiology, Institute of Postgraduate Education

ResearcherID: H-7787-2016; RSCI SPIN-code: 9180-6623

1 Partizan Zheleznyak Str., Krasnoyarsk Region, Krasnoyarsk 660022

R. F. Nasyrova
Bekhterev National Medical Research Centre for Psychiatry and Neurology
Russian Federation

Regina F. Nasyrova – Dr. Med. Sc., Senior Researcher, Head of the Department of Personalized Psychiatry and Neurology

RSCI SPIN-code: 1952-3043

3 Bekhterev Str., Saint Petersburg 192019


1. Karlov V.A., Freydkova N.V. Juvenile myoclonic epilepsy. In: Karlov V.A. (Ed.) Epilepsy in children and adult women and men. Мoscow: Meditsina; 2010 (in Russ.).

2. Ovchinnikova A.A., Gulyaev S.A., Gulyaeva S.E. et al. Heart rhythm disorder and epilepsy. Far East Medical Journal. 2016; 1: 54–8 (in Russ.).

3. Sadykova A.V., Shnayder N.A., Dmitrenko D.V. Ways of predicting and early detection of acute cardiovascular complications of antiepileptic therapy. Bulletine of Clinical Hospital No. 51. 2012; 5 (3): 66–8 (in Russ.).

4. Shnayder N.A. Some aspects of sudden death syndrome in epilepsy. Modern Technologies in Medicine. 2010; 5: 55–9 (in Russ.).

5. Russell A.E. Cessation of the pulse during the onset of epileptic fits. Lancet. 1906; 168 (4325): 152–4.

6. Stollberger C., Finsterer J. Cardiorespiratory findings in sudden unexplained death. Epilepsy Res. 2004; 59 (1): 51–60.

7. Shorvon S., Tomson T. Sudden unexpected death in epilepsy. Lancet. 2011; 378 (9808): 2028–38.

8. Berg A.T., Nickels K., Wirrell E.C., et al. Mortality risks in new-onset childhood epilepsy. Pediatrics. 2013; 132 (1): 124–31.

9. You C.F., Chong C.F., Wang T.L. et al. Unrecognized paroxysmal ventricular standstill masquerading as epilepsy: a Stokes-Adams attack. Epileptic Disord. 2007; 9 (2): 179–81.

10. Hunt J., Tang K. Long QT syndrome presenting as epileptic seizures in an adult. Emerg Med J. 2005; 22 (8): 600–1.

11. Tan H.L., Hou C.J., Lauer M.R., Sung R.J. Electrophysiologic mechanism of the long QT interval syndromes and torsades de pointes. Ann Intern Med. 1995; 122 (9): 701–14.

12. Surges R., Agjei P., Kallis C., et al. Pathological cardiac repolarization in pharmacoresistant epilepsy and its potential role in sudden sudden unexpected death in epilepsy: a case-control study. Epilepsia. 2010; 51 (2): 233–42.

13. Chahal C.A., Salloum M.N., Alahdab F., et al. Systematic review of the genetics of sudden unexpected death in epilepsy: potential overlap with sudden cardiac death and arrhythmia-related genes. J Am Heart Assoc. 2020; 9 (1): e012264.

14. Donner E.J. Sudden unexpected death in epilepsy: who are the children at risk? Paediatr Child Health. 2014; 19 (7): 389.

15. Scheffer I.E., Berkovic S., Capovilla G., et al. ILAE classification of the epilepsies: position paper of the ILAE Commission for Classification and Terminology. Epilepsia. 2017; 58 (4): 512–21.

16. Shilkina O.S., Schnaider N.A. Epidemiology of juvenile myoclonic epilepsy. Neurology, Neuropsychiatry, Psychosomatics. 2017; 9 (1S): 26–31. (in Russ.).

17. Shnayder N.A., Shilkina O.S., Petrov K.V., et al. Clinical and genetic heterogenity of juvenile myoclonic epilepsy. Epilepsy and Paroxysmal Conditions. 2016; 8 (2): 20–36. (in Russ.).

18. Karlov V.A., Zolovkina V.S. Problems of juvenile myoclonic epilepsy. A view through the prism of time. S.S. Korsakov Journal of Neurology and Psychiatry. 2017; 117 (9): 24–33. doi: 10.17116/jnevro20171179224-33 (in Russ.).

19. Caciagli L., Wandschneider B., Xiao F., et al. Abnormal hippocampal structure and function in juvenile myoclonic epilepsy and unaffected siblings. Brain. 2019; 142 (9): 2670–87.

20. Wandschneider B., Koepp M., Scott C., et al. Structural imaging biomarkers of sudden unexpected death in epilepsy. Brain. 2015; 138 (Pt 10): 2907–19.

21. Moskaleva P.V., Shilkina O.S., Shnayder N.A. Individual neuropsychological characteristics in patients with juvenile myoclonic epilepsy. Psychology in Russia: State of the Art. 2018; 11 (2): 42–54.

22. Salmina A.B., Shnayder N.A., Mikhutkina S.V. Modern concepts about the ion channels and chanellopathies. Siberian Medical Review. 2005; 1 (34): 75–8 (in Russ.).

23. Alekov A., Rahman M.M., Mitrovic N., et al. A sodium channel mutation causing epilepsy in man exhibits subtle defects in fast inactivation and activation in vitro. J Physiol. 2000; 529 (Pt 3): 533–9.

24. Vilin Y.Y., Ruben P.C. Slow inactivation in voltage-gated sodium channels: molecular substrates and contributions to channelopathies. Cell Biochem Biophys. 2001; 35 (2): 171–90.

25. Meisler M.H., Kearney J.A. Sodium channel mutations in epilepsy and other neurological disorders. J Clin Invest. 2005; 115 (8): 2010–7.

26. Ito M., Shirasaka Y., Hirose S., et al. Seizure phenotypes of a family with missense mutations in SCN2A. Pediatr Neurol. 2004; 31 (2): 150–2.

27. Aurlien D., Leren T.P., Taubøll E., Gjerstad L. New SCN5A mutation in a SUDEP victim with idiopathic epilepsy. Seizure. 2009; 18 (2): 158–60.

28. Littleton J.T., Ganetzky B. Ion channels and synaptic organization: analysis of the Drosophila genome. Neuron. 2000; 26 (1): 35–43.

29. Lehmann-Horn P., Jurkat-Rott K. Nanotechnology for neuronal ion channels. J Neurol Neurosurg Psychiatry. 2003; 74 (11): 1466–75.

30. Aiba I., Noebels J.L. Spreading depolarization in the brainstem mediates sudden cardiorespiratory arrest in mouse SUDEP models. Sci Transl Med. 2015; 7 (282): 282ra46.

31. Tu E., Bagnall R.D., Duflou J., Semsarian C. Post-mortem review and genetic analysis of sudden unexpected death in epilepsy (SUDEP) cases. Brain Pathol. 2011; 21 (2): 201–8.

32. Winkel B.G., Larsen M.K., Berge K.E., et al. The prevalence of mutations in KCNQ1, KCNH2, and SCN5A in an unselected national cohort of young sudden unexplained death cases. J Cardiovasc Electrophysiol. 2012; 23 (10): 1092–8.

33. Hartmann H.A., Colom L.V., Sutherland M.L., Noebels J.L. Selective localization of cardiac SCN5A sodium channels in limbic regions of rat brain. Nat Neurosci. 1999; 2 (7): 593–5.

34. Delgado-Escueta A.V. Advances in genetics of juvenile myoclonic epilepsies. Epilepsy Curr. 2007; 7 (3): 61–7.

35. Escayg A., Heils A., MacDonald B.T., et al. A novel SCN1A mutation associated with generalized epilepsy with febrile seizures plus – and prevalence of variants in patients with epilepsy. Am J Hum Genet. 2001; 68 (4): 866–73.

36. Jingami N., Matsumoto R., Ito H., et al. A novel SCN1A mutation in a cytoplasmic loop in intractable juvenile myoclonic epilepsy without febrile seizures. Epileptic Disord. 2014; 16 (2): 227–31.

37. Bhat M.A., Guru S.A., Mir R., et al. Role of SCN1A and SCN2A gene polymorphisms in epilepsy syndromes-A study from India. J Neurol Neurosci. 2018; 9 (1): 238.

38. Chan C.K., Low J.S., Lim K.S., et al. Whole exome sequencing identifies a novel SCN1A mutation in genetic (idiopathic) generalized epilepsy and juvenile myoclonic epilepsy subtypes. Neurol Sci. 2020; 41 (3): 591–8.

39. Anderson J.H., Bos J.M., Cascino G.D., Ackerman M.J. Prevalence and spectrum of electroencephalogram – identified epileptiform activity among patients with long QT syndrome. Heart Rhythm. 2014; 11 (1): 53–7.

40. Johnson J.N., Hofman N., Haglund C.M., et al. Identification of a possible pathogenic link between congenital long QT syndrome and epilepsy. Neurology. 2009; 72 (3): 224–31.

41. Goldman A.M., Behr E.R., Semsarian C., et al. Sudden unexpected death in epilepsy genetics: molecular diagnostics and prevention. Epilepsia. 2016; 57 (Suppl 1): 17–25.

42. Goldman A.M., Glasscock E., Yoo J., et al. Arrhythmia in heart and brain: KCNQ1 mutations link epilepsy and sudden unexplained death. Sci Transl Med. 2009; 1 (2): 2ra6.

43. Massey C.A., Sowers L.P., Dlouhy B.J., Richerson G.B. Mechanisms of sudden unexpected death in epilepsy: the pathway to prevention. Nat Rev Neurol. 2014; 10 (5): 271–82.

44. Goldman A.M. Mechanisms of sudden unexplained death in epilepsy. Curr Opin Neurol. 2015; 28 (2): 166–74.

45. Hata Y., Yoshida K., Kinoshita K., Nishida N. Epilepsy-related sudden unexpected death: targeted molecular analysis of inherited heart disease genes using next-generation DNA sequencing. Brain Pathol. 2017; 27 (3): 292–304.

46. Bagnall R.D., Crompton D.E., Petrovski S., et al. Exome-based analysis of cardiac arrhythmia, respiratory control, and epilepsy genes in sudden unexpected death in epilepsy. Ann Neurol. 2016; 79 (4): 522–34.

47. Genetic cardiological diseases. Сhannalopathies. Aavailable at: (accessed December 23, 2020) (in Russ.).


For citations:

Shnayder N.A., Petrova M.M., Petrov K.V., Dmitrenko D.V., Nasyrova R.F. Heart rate and conductivity disorders in juvenile myoclonic epilepsy: genetic predictors. Epilepsy and paroxysmal conditions. 2020;12(4):237-247. (In Russ.)

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ISSN 2311-4088 (Online)