Особенности фокальной кортикальной дисплазии при туберозном склерозе
https://doi.org/10.25557/2073-7998.2021.09.3-13
Аннотация
Туберозный склероз - орфанное аутосомно-доминантное наследственное заболевание, причиной которого являются инактивирующие мутации в генах TSC1 или TSC2, сопровождающиеся гиперактивацией сигнального пути mTOR, отвечающего за регуляцию роста, пролиферации, выживаемости клеток, а также аутофагии. Одним из основных клинических симптомов туберозного склероза является наличие туберов в головном мозге. Данные образования характеризуются нарушениями кортикальной ламинации, появлением аномальных нейронов и выраженным глиозом. Известно, что количество кортикальных туберов коррелирует с развитием нейропсихиатрических расстройств, в том числе фармакорезистентной эпилепсии. В данной статье освещены вопросы молекулярной генетики туберозного склероза, приведена гистопатологическая характеристика кортикальных туберов, рассмотрен молекулярный механизм морфогенеза кортикальных туберов, а также приведены данные о связи этих образований с развитием неврологических проявлений и методах их лечения.
Об авторах
Е. В. Бычкова
ГБОУ ВПО «Российский национальный исследовательский медицинский университет им. Н.И. Пирогова Минздрава России»
Россия
Россия
М. Ю. Дорофеева
Научно-исследовательский клинический институт педиатрии им. академика Ю.Е. Вельтищева, ФГАОУ ВО «РНИМУ им. Н. И. Пирогова Минздрава России»
Россия
Россия
В. В. Стрельников
ФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»
Россия
Россия
К. И. Аношкин
ФГБНУ «Медико-генетический научный центр имени академика Н.П. Бочкова»
Россия
Россия
Список литературы
1. Henske E.P., Józwiak S., Kingswood J.C., et al. Tuberous sclerosis complex. Nature Reviews Disease Primers. 2016;2:16035.
2. Saxton R.A., Sabatini D.M. mTOR Signaling in Growth, Metabolism, and Disease. Cell. 2017;168:960-976.
3. Curatolo P., Moavero R., de Vries P.J. Neurological and neuropsychiatric aspects of tuberous sclerosis complex. The Lancet Neurology. 2015;14:733-745.
4. Дорофеева М.Ю. Туберозный склероз. Диагностика и лечение. Москва: АДАРЕ; 2017. 292 с.
5. Feliciano D.M. The Neurodevelopmental Pathogenesis of Tuberous Sclerosis Complex (TSC). Frontiers in Neuroanatomy. 2020;14:39.
6. Gelot A.B., Represa A. Progression of Fetal Brain Lesions in Tuberous Sclerosis Complex. Frontiers in Neuroscience. 2020;14:899.
7. Salussolia C.L., Klonowska K., Kwiatkowski D.J., Sahin M. Genetic Etiologies, Diagnosis, and Treatment of Tuberous Sclerosis Complex. Annu Rev Genomics Hum Genet. 2019;20:217-240.
8. Lim K.C., Crino P.B. Focal malformations of cortical development: New vistas for molecular pathogenesis. Neuroscience. 2013;252:262-276.
9. Blair J.D., Hockemeyer D., Bateup H.S. Genetically engineered human cortical spheroid models of tuberous sclerosis. Nature Medicine. 2018;24:1568-1578.
10. Tee A.R., Sampson J.R., Pal D.K., Bateman J.M. The role of mTOR signalling in neurogenesis, insights from tuberous sclerosis complex. Seminars in Cell and Developmental Biology. 2016;52:12-20.
11. Mühlebner A., Iyer A.M., van Scheppingen J., et al. Specific pattern of maturation and differentiation in the formation of cortical tubers in tuberous sclerosis complex (TSC): Evidence from layer-specific marker expression. Journal of Neurodevelopmental Disorders. 2016;8:9
12. Way S.W., Mckenna J., Mietzsch U., et al. Loss of Tsc2 in radial glia models the brain pathology of tuberous sclerosis complex in the mouse. Human Molecular Genetics. 2009;18:1252-1265.
13. Foerster P., Daclin M., Asm S., et al. mTORC1 signaling and primary cilia are required for brain ventricle morphogenesis. Development (Cambridge). 2017;144:201-210.
14. Yasin S.A., Ali A.M., Tata M., et al. mTOR-dependent abnormalities in autophagy characterize human malformations of cortical development: Evidence from focal cortical dysplasia and tuberous sclerosis. Acta Neuropathologica. 2013;126:207-218.
15. Dibble C.C,. Elis W., Menon S., et al. TBC1D7 Is a Third Subunit of the TSC1-TSC2 Complex Upstream of mTORC1. Molecular Cell. 2012;47:535-546.
16. Martin K.R., Zhou W., Bowman M.J., et al. The genomic landscape of tuberous sclerosis complex. Nature Communications. 2017;8:15816.
17. Winden K.D., Sundberg M., Yang C., et al. Biallelic mutations in TSC2 lead to abnormalities associated with cortical tubers in human iPSC-derived neurons. Journal of Neuroscience. 2019;39:9294-9305.
18. Sancak O., Nellist M., Goedbloed M., et al. Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: Genotype-phenotype correlations and comparison of diagnostic DNA techniques in tuberous sclerosis complex. European Journal of Human Genetics. 2005;13:731-741.
19. Jansen F.E., Braams O., Vincken K.L.,, et al. Overlapping neurologic and cognitive phenotypes in patients with TSC1 or TSC2 mutations. Neurology. 2008;70:908-915.
20. Ogórek B., Hamieh L., Hulshof H.M., et al. TSC2 pathogenic variants are predictive of severe clinical manifestations in TSC infants: results of the EPISTOP study. Genetics in Medicine. 2020;22:1489-1497.
21. Overwater I.E., Swenker R., van der Ende E.L., et al. Genotype and brain pathology phenotype in children with tuberous sclerosis complex. European Journal of Human Genetics. 2016;24:1688-1695.
22. Chu-Shore C.J., Major P., Montenegro M., Thiele E. Cyst-like tubers are associated with TSC2 and epilepsy in tuberous sclerosis complex. Neurology. 2009;72:1165-1169.
23. Ding Y., Wang J., Zhou S., et al. Genotype and Phenotype Analysis of Chinese Children With Tuberous Sclerosis Complex: A Pediatric Cohort Study. Frontiers in Genetics. 2020;11:204.
24. Farach L.S., Pearson D.A., Woodhouse J.P., et al. Tuberous Sclerosis Complex Genotypes and Developmental Phenotype. Pediatric Neurology. 2019;96:58-63.
25. He J., Zhou W., Shi J., et al. Analysis of genotypes, EEG and phenotypes of tuberous sclerosis complex patients. National Medical Journal of China. 2020;100:136-140.
26. Mills J.D., Iyer A.M., van Scheppingen J., et al. Coding and small non-coding transcriptional landscape of tuberous sclerosis complex cortical tubers: Implications for pathophysiology and treatment. Scientific Reports. 2017;7:8089.
27. Boer K., Crino P.B., Gorter J.A., et al. Gene expression analysis of tuberous sclerosis complex cortical tubers reveals increased expression of adhesion and inflammatory factors. Brain Pathology. 2010;20:704-719.
28. Bagla S., Cukovic D., Asano E., et al. A distinct microRNA expression profile is associated with α[11C]-methyl-L-tryptophan (AMT) PET uptake in epileptogenic cortical tubers resected from patients with tuberous sclerosis complex. Neurobiology of Disease. 2018;109:76-87.
29. Dombkowski A.A., Batista C.E., Cukovic D., et al. Cortical Tubers: Windows into Dysregulation of Epilepsy Risk and Synaptic Signaling Genes by MicroRNAs. Cerebral Cortex. 2016;26:1059-1071.
30. Boer K., Troost D., Jansen F., et al. Clinicopathological and immunohistochemical findings in an autopsy case of tuberous sclerosis complex. Neuropathology. 2008;28:577-590.
31. Mizuguchi M. Abnormal giant cells in the cerebral lesions of tuberous sclerosis complex. Congenital Anomalies. 2007;47:2-8.
32. Wong M., Crino P.B. Tuberous sclerosis and epilepsy: Role of astrocytes. GLIA. 2012;60:1244-1250.
33. Zhang B., Zou J., Han L., et al. Microglial activation during epileptogenesis in a mouse model of tuberous sclerosis complex. Epilepsia. 2016;57:1317-1325.
34. Boer K., Jansen F., Nellist M., et al. Inflammatory processes in cortical tubers and subependymal giant cell tumors of tuberous sclerosis complex. Epilepsy Research. 2008;78:7-21.
35. Zimmer T.S., Broekaart D.W.M., Gruber V.E., et al. Tuberous Sclerosis Complex as Disease Model for Investigating mTOR-Related Gliopathy During Epileptogenesis. Frontiers in Neurology. 2020;11:1028.
36. Veersema T.J., de Neef A., van Scheppingen J., et al. Changes in vascular density in resected tissue of 97 patients with mild malformation of cortical development, focal cortical dysplasia or TSC-related cortical tubers. International Journal of Developmental Neuroscience. 2019;79:96-104.
37. Zhang M.N., Zou L.P., Wang Y.Y., et al. Calcification in cerebral parenchyma affects pharmacoresistant epilepsy in tuberous sclerosis. Seizure. 2018;60:86-90.
38. Mühlebner A., van Scheppingen J., Hulshof H.M., et al. Novel histopathological patterns in cortical tubers of epilepsy surgery patients with tuberous sclerosis complex. PLoS ONE. 2016;11.
39. Chu-Shore C.J., Frosch M.P., Grant P.E., Thiele E.A. Progressive multifocal cystlike cortical tubers in tuberous sclerosis complex: Clinical and neuropathologic findings. Epilepsia. 2009;50:2648-2651.
40. Curatolo P., Jóźwiak S., Nabbout R. Management of epilepsy associated with tuberous sclerosis complex (TSC): Clinical recommendations. European Journal of Paediatric Neurology. 2012;16:738-748.
41. Jansen F.E., Vincken K.L., Algra A., et al. Cognitive impairment in tuberous sclerosis complex is a multifactorial condition. Neurology. 2008;70:916-923.
42. Kannan L., Vogrin S., Bailey C., et al. Centre of epileptogenic tubers generate and propagate seizures in tuberous sclerosis. Brain. 2016;139:2653-2667.
43. French J.A., Lawson J.A., Yapici Z., et al. Adjunctive everolimus therapy for treatment-resistant focal-onset seizures associated with tuberous sclerosis (EXIST-3): a phase 3, randomised, double-blind, placebo-controlled study. The Lancet. 2016;388:2153-2163.
44. Wong M. The role of glia in epilepsy, intellectual disability, and other neurodevelopmental disorders in tuberous sclerosis complex. Journal of Neurodevelopmental Disorders. 2019;11:30.
45. Tye C., Mcewen F.S., Liang H., et al. Long-term cognitive outcomes in tuberous sclerosis complex. Developmental Medicine and Child Neurology. 2020;62:322-329.
46. Kotulska K., Kwiatkowski D.J., Curatolo P., et al. Prevention of Epilepsy in Infants with Tuberous Sclerosis Complex in the EPISTOP Trial. Annals of Neurology. 2021;89:304-314.
47. Sarbassov D.D., Ali S.M., Sengupta S., et al. Prolonged Rapamycin Treatment Inhibits mTORC2 Assembly and Akt/PKB. Molecular Cell. 2006;22:159-168.
48. Sadowski K., Kotulska-Jóźwiak K., Jóźwiak S. Role of mTOR inhibitors in epilepsy treatment. Pharmacological Reports. 2015;67:636-646.
49. Lu D.S., Karas P.J., Krueger D.A., Weiner H.L. Central nervous system manifestations of tuberous sclerosis complex. American Journal of Medical Genetics, Part C: Seminars in Medical Genetics. 2018;178:291-298.
50. Fallah A., Weil A.G., Sur S., et al. Epilepsy surgery related to pediatric brain tumors: Miami Children’s hospital experience. Journal of Neurosurgery: Pediatrics. 2015;16:675-680.
Рецензия
Для цитирования:
Бычкова Е.В., Дорофеева М.Ю., Стрельников В.В., Аношкин К.И. Особенности фокальной кортикальной дисплазии при туберозном склерозе. Медицинская генетика. 2021;20(9):3-13. https://doi.org/10.25557/2073-7998.2021.09.3-13
For citation:
Bychkova E.V., Dorofeeva M.I., Strelnikov V.V., Anoshkin K.I. Characteristics of cortical tubers in tuberous sclerosis. Medical Genetics. 2021;20(9):3-13. (In Russ.) https://doi.org/10.25557/2073-7998.2021.09.3-13
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