nnpNeurology, Neuropsychiatry, PsychosomaticsНеврология, нейропсихиатрия, психосоматика2074-27112310-1342"IMA-Press", LLC10.14412/2074-2711-2017-1S-74-77nnp-731Research ArticleCLINICAL OBSERVATIONSКЛИНИЧЕСКИЕ НАБЛЮДЕНИЯA clinical case of epilepsy in a female patient with double mutations in the SCN2A and PCDH19 genesКлинический случай эпилепсии у пациентки с двойной мутацией в генах SCN2A и PCDH19МироновМ. Б.MironovM. B.

Department of Clinical Physiology and Functional Diagnosis, 91, Volokolamskoe Shosse, Moscow 123371;

74, Michurinsky Prospect, Moscow 119602

БобыловаМ. Ю.BobylovaM. Yu.

119579 Москва, ул. Академика Анохина, 9

9, Academician Anokhin St., Moscow 119579

БурдС. Г.BurdS. G.

119602 Москва, Мичуринский проспект, 74;

Кафедра неврологии, нейрохирургии и медицинской генетики лечебного факультета, 117997 Москва, ул. Островитянова, 1

74, Michurinsky Prospect, Moscow 119602;

Department of Neurology, Neurosurgery, and Medical Genetics, Faculty ofGeneral Medicine, 1, Ostrovityanov St., Moscow 117997

КрасильщиковаТ. М.KrasilshchikovaT. M.

Кафедра неврологии, нейрохирургии и медицинской генетики педиатрического факультета,

117997 Москва, ул. Островитянова, 1

Department of Neurology, Neurosurgery, and Medical Genetics, Faculty of Pediatrics, 

1, Ostrovityanov St., Moscow 117997

ГунченкоМ. М.GunchenkoM. M.

119602 Москва, Мичуринский проспект, 74

74, Michurinsky Prospect, Moscow 119602

СаржинаМ. Н.SarzhinaM. N.

119602 Москва, Мичуринский проспект, 74

74, Michurinsky Prospect, Moscow 119602

БатышеваТ. Т.BatyshevaT. T.

119602 Москва, Мичуринский проспект, 74

74, Michurinsky Prospect, Moscow 119602

ФГБОУ ДПО «Институт повышения квалификации Федерального медико-биологического агентства»; Научно-практический центр детской психоневрологии Департамента здравоохранения города МосквыРоссияInstitute of Advanced Training, Federal Biomedical Agency; Research and Practical Center of Pediatric Psychoneurology, Moscow Healthcare DepartmentRussian FederationИнститут детской и взрослой неврологии и эпилепсии им. Святителя ЛукиРоссияSaint Luke Institute of Pediatric and Adult Neurology and EpilepsyRussian FederationНаучно-практический центр детской психоневрологии Департамента здравоохранения города Москвы; ФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава РоссииРоссияResearch and Practical Center of Pediatric Psychoneurology, Moscow Healthcare Department; N.I. Pirogov Russian National Research Medical University, Ministry of Health of RussiaRussian FederationФГБОУ ВО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова» Минздрава РоссииРоссияN.I. Pirogov Russian National Research Medical University, Ministry of Health of RussiaRussian FederationНаучно-практический центр детской психоневрологии Департамента здравоохранения города МосквыРоссияResearch and Practical Center of Pediatric Psychoneurology, Moscow Healthcare DepartmentRussian Federation20171406201791SSPECIAL ISSUE: EPILEPSY7477Copyright © Mironov M.B., Bobylova M.Y., Burd S.G., Krasilshchikova T.M., Gunchenko M.M., Sarzhina M.N., Batysheva T.T., 20172017Миронов М.Б., Бобылова М.Ю., Бурд С.Г., Красильщикова Т.М., Гунченко М.М., Саржина М.Н., Батышева Т.Т.Mironov M.B., Bobylova M.Y., Burd S.G., Krasilshchikova T.M., Gunchenko M.M., Sarzhina M.N., Batysheva T.T.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://nnp.ima-press.net/nnp/article/view/731

The paper describes a 6-year-old female patient with epilepsy caused by mutations in the SCN2A and PCDH19 genes, which clinically appears as epileptic seizures, drug-resistant epilepsy, secondary microcephaly, mental retardation, and autism. It reviews the literature regarding both mutations. World literature lacks publications on a combination of two SCN2A and PCDH19 mutations in one female patient with epileptic encephalopathies.

Представлено описание пациентки 6 лет с эпилепсией, обусловленной мутациями в генах SCN2A и PCDH19, клинически проявляющейся эпилептическими приступами, фармакорезистентным течением эпилепсии, вторичной микроцефалией, задержкой психоречевого развития и аутизмом. Проведен обзор литературы, касающейся обеих мутаций. Публикаций на тему сочетания двух мутаций эпилептических энцефалопатий SCN2A и PCDH19 у одной пациентки в мировой литературе не обнаружено.

генетические эпилептические энцефалопатии у детейэпилепсиявидео-электроэнцефалографический мониторингчастые и тяжелые эпилептические приступымежприступная эпилептиформная активность на электроэнцефалограммевыраженная задержка развития с аутистическим поведениемgenetic epileptic encephalopathies in childrenepilepsyvideo EEG monitoringfrequent and severe epileptic seizuresinterictal epileptiform EEG activityobvious growth retardation with autistic behaviorReferencesStriano P, de Jonghe P, Zara F. Genetic epileptic encephalopathies: is all written into the DNA? Epilepsia. 2013 Nov;54 Suppl 8:22-6. doi: 10.1111/epi.12419Striano P, de Jonghe P, Zara F. Genetic epileptic encephalopathies: is all written into the DNA? Epilepsia. 2013 Nov;54 Suppl 8:22-6. doi: 10.1111/epi.12419Mastrangelo M, Leuzzi V. Genes of earlyonset epileptic encephalopathies: from genotype to phenotype. Pediatr Neurol. 2012 Jan;46(1): 24-31. doi: 10.1016/j.pediatrneurol.2011.11.003Mastrangelo M, Leuzzi V. Genes of earlyonset epileptic encephalopathies: from genotype to phenotype. Pediatr Neurol. 2012 Jan;46(1): 24-31. doi: 10.1016/j.pediatrneurol.2011.11.003Berkovic SF. Genetics of epilepsy in clinical practice. Epilepsy Curr. 2015 Jul-Aug;15(4):192-6. doi: 10.5698/1535-7511-15.4.192Berkovic SF. Genetics of epilepsy in clinical practice. Epilepsy Curr. 2015 Jul-Aug;15(4):192-6. doi: 10.5698/1535-7511-15.4.192McTague A, Howell KB, Cross JH, et al. The genetic landscape of the epileptic encephalopathies of infancy and childhood. Lancet Neurol. 2016 Mar;15(3):304-16. doi: 10.1016/S1474-4422(15)00250-1. Epub 2015 Nov 17.McTague A, Howell KB, Cross JH, et al. The genetic landscape of the epileptic encephalopathies of infancy and childhood. Lancet Neurol. 2016 Mar;15(3):304-16. doi: 10.1016/S1474-4422(15)00250-1. Epub 2015 Nov 17.Patel J, Mercimek-Mahmutoglu S. Epileptic encephalopathy in childhood: A stepwise approach for identification of underlying genetic causes. Indian J Pediatr. 2016 Oct;83(10):1164-74. doi: 10.1007/s12098-015-1979-9. Review. PMID: 2682154.Patel J, Mercimek-Mahmutoglu S. Epileptic encephalopathy in childhood: A stepwise approach for identification of underlying genetic causes. Indian J Pediatr. 2016 Oct;83(10):1164-74. doi: 10.1007/s12098-015-1979-9. Review. PMID: 2682154.Berkovic SF, Heron SE, Giordano L, et al. Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy. Ann Neurol. 2004;55:550-7. doi: 10.1002/ana.20029Berkovic SF, Heron SE, Giordano L, et al. Benign familial neonatal-infantile seizures: characterization of a new sodium channelopathy. Ann Neurol. 2004;55:550-7. doi: 10.1002/ana.20029Ogiwara I, Ito K, Sawaishi Y, et al. De novo mutations of voltage-gated sodium channel alpha-II gene SCN2A in intractable epilepsies. Neurology. 2009;73:1046-53. doi: 10.1212/WNL.0b013e3181b9cebcOgiwara I, Ito K, Sawaishi Y, et al. De novo mutations of voltage-gated sodium channel alpha-II gene SCN2A in intractable epilepsies. Neurology. 2009;73:1046-53. doi: 10.1212/WNL.0b013e3181b9cebcKamiya K, Kaneda M, Sugawara T, et al. A nonsense mutation of the sodium channel gene SCN2A in a patient with intractable epilepsy and mental decline. J Neurosci. 2004;24:2690-8. doi: 10.1523/JNEUROSCI.3089-03.2004Kamiya K, Kaneda M, Sugawara T, et al. A nonsense mutation of the sodium channel gene SCN2A in a patient with intractable epilepsy and mental decline. J Neurosci. 2004;24:2690-8. doi: 10.1523/JNEUROSCI.3089-03.2004Liao Y, Deprez L, Maljevic S, et al. Molecular correlates of age-dependent seizures in an inherited neonatal-infantile epilepsy. Brain. 2010;133:1403-14. doi: 10.1093/brain/awq057Liao Y, Deprez L, Maljevic S, et al. Molecular correlates of age-dependent seizures in an inherited neonatal-infantile epilepsy. Brain. 2010;133:1403-14. doi: 10.1093/brain/awq057Sanders SJ, Murtha MT, Gupta AR, et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature. 2012;485:237-41. doi: 10.1038/nature10945Sanders SJ, Murtha MT, Gupta AR, et al. De novo mutations revealed by whole-exome sequencing are strongly associated with autism. Nature. 2012;485:237-41. doi: 10.1038/nature10945Tavassoli T, Kolevzon A, Wang AT, et al. De novo SCN2A splice site mutation in a boy with autism spectrum disorder. BMC Med Genet. 2014;15:35. doi: 10.1186/1471-2350-15-35Tavassoli T, Kolevzon A, Wang AT, et al. De novo SCN2A splice site mutation in a boy with autism spectrum disorder. BMC Med Genet. 2014;15:35. doi: 10.1186/1471-2350-15-35Bergren SK, Chen S, Galecki A, Kearney JA. Genetic modifiers affecting severity of epilepsy caused by mutation of sodium channel SCN2A. Mammalian Genome. 2005;16(9):683-90. doi: 10.1007/s00335-005-0049-4Bergren SK, Chen S, Galecki A, Kearney JA. Genetic modifiers affecting severity of epilepsy caused by mutation of sodium channel SCN2A. Mammalian Genome. 2005;16(9):683-90. doi: 10.1007/s00335-005-0049-4Dibbens LM, Tarpey PS, Hynes K, et al. X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment. Nat Genet. 2008;40:776-81. doi: 10.1038/ng.149Dibbens LM, Tarpey PS, Hynes K, et al. X-linked protocadherin 19 mutations cause female-limited epilepsy and cognitive impairment. Nat Genet. 2008;40:776-81. doi: 10.1038/ng.149Duszyc K, Terczynska I, HoffmanZacharska D. Epilepsy and mental retardation restricted to females: X-linked epileptic infantile encephalopathy of unusual inheritance. J Appl Genet. 2015;56(1):49-56. doi: 10.1007/s13353-014-0243-8Duszyc K, Terczynska I, HoffmanZacharska D. Epilepsy and mental retardation restricted to females: X-linked epileptic infantile encephalopathy of unusual inheritance. J Appl Genet. 2015;56(1):49-56. doi: 10.1007/s13353-014-0243-8Depienne C, Bouteiller D, Keren B, et al. Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females. PLoS Genet. 2009 Feb;5(2):e1000381. doi: 10.1371/journal.pgen.1000381Depienne C, Bouteiller D, Keren B, et al. Sporadic infantile epileptic encephalopathy caused by mutations in PCDH19 resembles Dravet syndrome but mainly affects females. PLoS Genet. 2009 Feb;5(2):e1000381. doi: 10.1371/journal.pgen.1000381Gagliardi M, Annesi G, Sesta M, et al. PCDH19 mutations in female patients from Southern Italy. Seizure. 2015 Jan;24:118-20. doi: 10.1016/j.seizure.2014.08.010Gagliardi M, Annesi G, Sesta M, et al. PCDH19 mutations in female patients from Southern Italy. Seizure. 2015 Jan;24:118-20. doi: 10.1016/j.seizure.2014.08.010Cappelletti S, Specchio N, Moavero R, et al. Cognitive development in females with PCDH19 gene-related epilepsy. Epilepsy Behavior. 2015;42:36-40. doi: 10.1016/j.yebeh.2014.10.019Cappelletti S, Specchio N, Moavero R, et al. Cognitive development in females with PCDH19 gene-related epilepsy. Epilepsy Behavior. 2015;42:36-40. doi: 10.1016/j.yebeh.2014.10.019

The authors declare that there are no conflicts of interest present.