Preview

Russian Journal of Child Neurology

Advanced search

Dynamics of management of monogenic epilepsies, developmental and epileptic encephalopathies in routine clinical practice

https://doi.org/10.17650/2073-8803-2024-19-4-10-19

Abstract

Background. There is no doubt that genetic testing should be one of the main studies in modern clinical diagnosis of epileptic syndromes.

Aim. To describe and compare the spectrum of detected gene mutations in patients with epilepsy and developmental and epileptic encephalopathies (DEE) over the last 3 years of clinical practice of neurologists-epileptologists, including: analysis of diagnosed epileptic syndromes, timing of etiological diagnosis, treatment options and effectiveness.

Materials and methods. A multicenter retrospective study including patients of any age and gender with epilepsy or DEE (with the obligatory presence of epileptic seizures) and verified gene mutations. The analysis was carried out as of 2020 and 2023. Over a three-year period, the number of data received in the study increased and amounted to 100 and 205 patients, respectively, 87–90 % of whom were children under 18 years of age.

Results and discussion. Over a three-year period, the number of genes with mutations increased from 67 to 98 variants. The clear leader remains mutations in the SCN1A gene. In practice, the number of referrals for whole exome sequencing has doubled from 9 to 18.6 % and the proportion of patients with mutation confirmation by Sanger sequencing has doubled from 32 % to 50.7 %. Up to 68 % of patients with a confirmed gene mutation are patients with one or another variant of DEE. Approaches to therapy with antiepileptic drugs have not undergone significant changes. but the volume of alternative methods decreased slightly from 52 to 45 %, with an emerging trend toward an increase in the effectiveness of therapy (an increase in the percentage of patients with no seizures from 46 to 54 %).

Conclusion. Analytical processing and expansion of experience in the etiological diagnosis of monogenic epilepsies and DEE is reflected in a more targeted selection and effectiveness of therapy for this category of patients.

About the Authors

О. A. Rakhmanina
Tyumen State Medical University, Ministry of Health of Russia
Russian Federation

Olga Aleksandrovna Rakhmanina

54 Odesskaya St., Tyumen 625023



I. V. Volkov
Sibneiromed LLC
Russian Federation

5 Vokzalnaya Magistral St., Novosibirsk 630091



Т. R. Tomenko
European medical center “UMMC-Health” LLC; Ural State Medical University, Ministry of Health of Russia
Russian Federation

113 Sheinkmana St., Yekaterinburg 620144

3 Repina St., Yekaterinburg 620028



O. I. Shestakova
Omsk State Medical University, Ministry of Health of Russia
Russian Federation

12 Lenina St., Omsk 644099



О. К. Volkova
Sibneiromed LLC; Children’s City Clinical Hospital of Emergency Medical Care
Russian Federation

5 Vokzalnaya Magistral St., Novosibirsk 630091

3 Krasnyy Prospekt, Novosibirsk 630091



References

1. Belousova E.D., Groznova O.S., Voinova V.Yu. Whole genome sequencing in children with epilepsy and developmental disorders. Rossiyskiy vestnik perinatologii i pediatrii = Russian Bulletin of Perinatology and Pediatrics 2024;69(2):56–64. (In Russ.). DOI: 10.21508/1027-4065-2024-69-2-56-64

2. Belousova E.D., Sharkov A.A. Difficulties in the diagnosis, prognosis and treatment of genetic epileptic encephalopathies: the view of a neurologist. Zhurnal Nevrologii i Psikhiatrii im. S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry 2019;119(11):34–40. (In Russ.). DOI: 10.17116/jnevro201911911234

3. Belousova E.D. Genetics of epilepsy: What for and how to examine children with epilepsy. Nevrologiya, neyropsikhiatriya, psikhosomatika = Neurology, Neuropsychiatry, Psychosomatics 2014;(special issue 1): 4–8. (In Russ.). DOI: 10.14412/2074-2711-2014-1S-4-8

4. Gamirova R.G., Gamirova R.R., Esin R.G. Genetics of epilepsy: successes, problems and development prospects. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry 2020;120(9):144–50. (In Russ.). DOI: 10.17116/jnevro2020120091144

5. Dadali E.L., Konovalov F.A., Akimova I.A. et al. Early epileptic encephalopathy associated with SCN2A mutations: clinical and genetic description of eight novel patients. Nervno-myshechnye bolezni = Neuromuscular Diseases 2018;8(2):42–52. (In Russ.). DOI: 10.17650/2222-8721-2018-8-2-42-52

6. Dadali E.L., Sharkov A.A., Sharkova I.V. et al. Hereditary diseases and syndromes accompanied by febrile convulsions: clinical and genetic characteristics and diagnostic procedures. Russkiy zhurnal detskoy nevrologii = Russian Journal of Child Neurology 2016;11(2):33–41. (In Russ.). DOI: 10.17650/2073-8803-2016-11-2-33-41

7. Kozhanova T.V., Zhilina S.S., Mescheryakova T.I. et al. Significance of exome sequencing for diagnosis of epilepsy in children. Epilepsiya i paroksizmalnye sostoyaniya = Epilepsy and Paroxysmal Conditions 2019;11(4):379–87. (In Russ.). DOI: 10.17749/2077-8333.2019.11.4.379-387

8. Mukhin K.Yu., Pylaeva O.A. New classification of epileptic syndromes by the International League Against Epilepsy (2022): basic definitions and principles; differences from the draft classification; comments and discussion. Vestnik epileptologii = Bulletin of Epileptology 2022;4–14. (In Russ.).

9. Mukhin K.Yu., Pylaeva O.A., Kakaulina V.S., Bobylova M.Yu. Classification and definition of epilepsy. Position paper by the International League Against Epilepsy on Nosology and Definitions of Epilepsy Syndromes dated 2021. Russkiy zhurnal detskoy nevrologii = Russian Journal of Child Neurology 2022;17(1): 6–95. (In Russ.). DOI: 10.17650/2073-8803-2022-17-1-6-95

10. Rakhmanina O.A., Volkov I.V., Shestakova O.I. et al. Experience in the management of patients with genetic epilepsies and epileptic encephalopathies in the outpatient practice. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry 2021;121(2):99–105. (In Russ.). DOI: 10.17116/jnevro202112102199

11. Rakhmanina O.A., Levitina E.V., Velizhanina S.E. The share of epileptic encephalopathies in the structure of epilepsies and epileptic syndromes in children. Rossiyskiy vestnik perinatologii i pediatrii = Russian Bulletin of Perinatology and Pediatrics 2019;64(4):259, 260. (In Russ.). DOI: 10.21508/1027-4065-congress-2019

12. Semenova N.A., Dadali E.L., Sharkov A.A., Akimova I.A. Clinical and genetic characteristics and diagnosis of hereditary variants of neonatal epilepsy. Nervno-myshechnye bolezni = Neuromuscular Diseases 2017;7(3):36–42. (In Russ.). DOI: 10.17650/2222-8721-2017-7-3-36-42

13. Sharkov A.A., Sharkova I.V., Belousova E.I. et al. Genetics and treatment of early infantile epileptic encephalopathies. Zhurnal nevrologii i psikhiatrii im. S.S. Korsakova = S.S. Korsakov Journal of Neurology and Psychiatry 2016;9(2):67–73. (In Russ.). DOI: 10.17116/jnevro20161169267-73

14. Berkovic S.F. Genetics of epilepsy in clinical practice. Epil Curr 2015;15:192–6. DOI: 10.5698/1535-7511-15.4.19

15. Kato M., Yamagata T., Kubota M. et al. Clinical spectrum of early onset epileptic encephalopathies caused by KCNQ2 mutation. Epilepsia 2013;54(7):1282–7. DOI: 10.1111/epi.12200

16. Kwan P., Brodie M.J. Early identification of refractory epilepsy. N Engl J Med 2000;342(5):314–9. DOI: 10.1056/NEJM200002033420503

17. Ream M.A., Patel A.D. Obtaining genetic testing in pediatric epilepsy. Epilepsia 2015;56(10):1505–14. DOI: 10.1111/epi.13122

18. Sisodiya S.M. Genetic screening and diagnosis in epilepsy? Curr Opin Neurol 2015;28(2):136–42. DOI: 10.1097/WCO.0000000000000180

19. Snoeijen-Schouwenaars F.M., van Ool J.S., Verhoeven J.S. et al. Diagnostic exome sequencing in 100 consecutive patients with both epilepsy and intellectual disability. Epilepsia 2019;60(1):155–64. DOI: 10.1111/epi.14618

20. Wang J., Lin Z.J., Liu L. et al. Epilepsy-associated genes. Seizure 2017;44:11–20. DOI: 10.1016/j.seizure.2016.11.030


Review

For citations:


Rakhmanina О.A., Volkov I.V., Tomenko Т.R., Shestakova O.I., Volkova О.К. Dynamics of management of monogenic epilepsies, developmental and epileptic encephalopathies in routine clinical practice. Russian Journal of Child Neurology. 2024;19(4):10-19. (In Russ.) https://doi.org/10.17650/2073-8803-2024-19-4-10-19

Views: 287


Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.


ISSN 2073-8803 (Print)
ISSN 2412-9178 (Online)