actabiomedicaActa Biomedica ScientificaActa Biomedica Scientifica2541-94202587-9596Scientific Centre for Family Health and Human Reproduction Problems10.29413/ABS.2019-4.3.4actabiomedica-2082Research ArticleГЕНЕТИКА, ПРОТЕОМИКА И МЕТАБОЛОМИКАGENETICS, PROTEOMICS AND METABOLOMICSВрождённый спастический церебральный паралич: генетические аспекты патогенезаGenetic Aspects of Pathogenesis of Congenital Spastic Cerebral Paralysishttps://orcid.org/0000-0001-8899-4107ПритыкоА. Г.PritykoA. G.

Притыко Андрей Георгиевич – доктор медицинских наук, профессор, директор

119619, г. Москва, ул. Авиаторов, 38

Andrey G. Prityko – Dr. Sc. (Med.), Professor, Director

 

npcprakt@mail.ruhttps://orcid.org/0000-0002-8344-500XЧебаненкоН. В.ChebanenkoN. V.

Чебаненко Наталья Владимировна – кандидат медицинских наук, заведующая отделением общей психоневрологии

119619, г. Москва, ул. Авиаторов, 38

Natalya V. Chebanenko – Cand. Sc. (Med.), Head of the Department of General Psychoneurology

ul. Aviatorov 38, Moscow 119619

npcprakt@mail.ruhttps://orcid.org/0000-0002-0625-1404СоколовП. Л.SokolovP. L.

Соколов Павел Леонидович – доктор медицинских наук, ведущий научный сотрудник отдела лучевой диагностики

119619, г. Москва, ул. Авиаторов, 38

Pavel L. Sokolov – Dr. Sc. (Med.), Leading Research Officer at the Department of Radiation Diagnostics

ul. Aviatorov 38, Moscow 119619

psok.sci@gmail.comhttps://orcid.org/0000-0002-1401-5479ЗыковВ. П.ZykovV. P.

Зыков Валерий Петрович – доктор медицинских наук, профессор, заведующий кафедрой неврологии детского возраста 

125373, г. Москва, ул. Героев Панфиловцев, 28

Valery P. Zykov – Dr. Sc. (Med.), Professor, Head of the Department of Children Neurology

ul. Geroev Panfilovtsev 28, Moscow 125373

rmapo@rmapo.ruКлимчукО. В.KlimchukO. V.

Климчук Олег Владимирович – кандидат медицинских наук, заведующий отделом лучевой диагностики 

119619, г. Москва, ул. Авиаторов, 38

Oleg V. Klimchuk – Cand. Sc. (Med.), Head of the Department of Radiation Diagnostics

ul. Aviatorov 38, Moscow 119619

https://orcid.org/0000-0001-5821-9783КанивецИ. В.KanivetsI. V.

Канивец Илья Вячеславович – кандидат медицинских наук, врач-генетик, руководитель отдела генетики медико-генетического центра 

115093, г. Москва, Подольское шоссе, д. 8, корп. 5

Ilya V. Kanivets – Cand. Sc. (Med.), Geneticist, Head of the Genetics Department

Podolskoye shosse build. 8, korp. 5, Moscow 5115093

ГБУЗ «Научно-практический центр специализированной помощи детям имени Н.В. Войно-Ясенецкого Департамента здравоохранения г. Москвы»Scientific-Practical Center for Specialized Assistance for Children named after N.V. Voino-Yasenetsky of Department of Healthcare of MoscowКафедра неврологии детского возраста ФГБОУ ДПО «Российская медицинская академия непрерывного профессионального образования» Минздрава РоссииDepartment of Children’s Neurology, Russian Medical Academy of Continuing Professional EducationООО «Геномед»OOO Genomed201915072019432839Copyright © Притыко А.Г., Чебаненко Н.В., Соколов П.Л., Зыков В.П., Климчук О.В., Канивец И.В., 20192019Притыко А.Г., Чебаненко Н.В., Соколов П.Л., Зыков В.П., Климчук О.В., Канивец И.В.Prityko A.G., Chebanenko N.V., Sokolov P.L., Zykov V.P., Klimchuk O.V., Kanivets I.V.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.actabiomedica.ru/jour/article/view/2082

Врождённый спастический церебральный паралич представляет собой большую группу непрогрессирующих расстройств нервной системы, в основе которой лежат воздействия многих факторов. Многообразие клинической картины заболевания и синдромальный принцип классифицирования определяют массу неясностей и неопределенностей в диагностике состояний данной группы. Мультифакториальность лежащих в основе поражений головного мозга очевидна и не вызывает сомнений. Накопленный к настоящему времени объём информации не позволяет исключить роль и значимость непосредственного воздействия острой асфиксии в родах на нормально сформированный в процессе беременности плод, роли инфекционных поражений головного мозга, нарушений нейрональной миграции. Столь же затруднительно проигнорировать зависимость клинической картины заболевания от того, на каком этапе онтогенеза происходит воздействие повреждающего агента. Как один из патогенетических факторов справедливо рассматривается генетическая детерминированность фенотипа клинической картины заболевания. Настоящий обзор посвящён генетическим аспектам патогенеза этой патологии. Подробно проанализирована информация по моногенным механизмам наследования. Отдельно рассмотрены данные близнецовых исследований. В рамках проводимого изучения полиморфизмов прослежено их влияние на гемостаз, иммунореактивность и формирование воспалительных реакций. Проанализированы данные о влиянии полиморфизмов на молекулярные механизмы, лежащие в основе повреждающего воздействия ишемии, как на уровне нейроглии, так и на уровне нейрона. Рассмотрено влияние на формирование фенотипа детского церебрального паралича полиморфизма генов, регулирующих обмен липопротеинов и транспортных мембранных белков. Отдельно рассматриваются эпигенетические влияния на формирование фенотипа врождённого церебрального паралича, механизмы их реализации и перспективы коррекции генома с помощью молекулярных технологий.

Congenital spastic cerebral palsy (СР) is a large group of non-progressive disorders of the nervous system. The basis of the pathogenesis of these conditions is considered the impact of many factors. The clinical diversity of the disease and the syndromic principle of classification determine the existing uncertainties in the diagnosis of these diseases. The multifactorial nature of the underlying brain lesions is obvious and beyond doubt. The volume of information accumulated to date does not allow one to exclude the role and significance of the direct effect of acute asphyxiation in childbirth on a fetus normally formed during pregnancy, the role of infectious brain lesions, and disorders of neuronal migration. It is impossible to ignore the dependence of the clinical picture of the disease on what stage of ontogenesis the impact of the damaging agent occurs. As one of the pathogenetic factors, the genetic determinism of the phenotype of the clinical picture of a disease is fairly considered. This review focuses on the genetic aspects of the pathogenesis of this pathology. The information on monogenic mechanisms of inheritance is analyzed in detail. Such genetically determined mechanisms of pathogenesis as the inheritance of prerequisites for brain trauma in the perinatal period are considered separately. The new clinically significant variants of chromosomal mutations found in patients with CР are reviewed in detail,  the evidence of the influence of genetic factors on the development of cerebral palsy in the absence of a pronounced monogenic cause of the disease, obtained through twin studies, is reviewed.  Lit search of polymorphisms markers of predisposition to the development of cerebral palsy genes of the folate cycle, genes of glutamate receptors, the gene of apolipoprotein and of the gene for the transcription factor of oligodendrocytes (OLIG2) in Detail the role of epigenetic effects on the activity of genes coding for mitochondrial proteins.

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