Features of brain involvement in tuberous sclerosis patients in the Republic of Bashkortostan

Mustafin R.N.

doi:https://doi.org/10.17116/jnevro202612603181

Mustafin R.N.

Bashkir State Medical University, Ufa, Russia

ORCID: 0000-0002-4091-382X

Features of brain involvement in tuberous sclerosis patients in the Republic of Bashkortostan

Authors:

Mustafin R.N.

More about the authors

Journal: S.S. Korsakov Journal of Neurology and Psychiatry. 2026;126(3): 81‑86

DOI: 10.17116/jnevro202612603181

Read: 351 times

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To cite this article:

Mustafin RN. Features of brain involvement in tuberous sclerosis patients in the Republic of Bashkortostan. S.S. Korsakov Journal of Neurology and Psychiatry. 2026;126(3):81‑86. (In Russ.)
https://doi.org/10.17116/jnevro202612603181

Подписка 2026 Журнал неврологии и психиатрии им. С.С. Корсакова (S.S. Korsakov Journal of Neurology and Psychiatry)

Использование инфографики авторами научных работ

OBJECTIVE

To identify the features of brain involvement and to characterize the genetic causes of tuberous sclerosis (TS) in patients in the Republic of Bashkortostan.

MATERIAL AND METHODS

A retrospective analysis of data on patients with TS registered with geneticists of the Republican Medical Genetic Center for the period from 2012 to 2025 was performed.

RESULTS

The prevalence of TS in the republic was 2.12 per 100.000 population. Subependymal giant cell astrocytoma was detected in 19%, epilepsy in 67%, subependymal hamartomas in 66%, and cortical tubers in 43% of patients. Cognitive deficits were present in 47% of patients, while autism spectrum disorders were found in only 1%. Mutations were identified in the TSC1 gene in 5 patients, the TSC2 gene in 19 patients, and extended deletions of the TSC2 gene in 4 patients.

DISCUSSION

TS prevalence in the region is 5.24 times lower than the global average. The frequencies of cortical tubers, subependymal nodes, cognitive deficits, and autism spectrum disorders are also significantly lower than those reported in international meta-analyses. No data were available on behavioral disorders or attention-deficit hyperactivity disorder. Five TSC1 gene mutations (three de novo) and 19 TSC2 gene mutations (one de novo) were reported. Eight patients received targeted therapy.

CONCLUSION

Raising awareness of TS among physicians in all specialties is essential to ensure comprehensive case reporting. Genetic confirmation of TS enables effective treatment with mTOR inhibitors. All TS patients should consult a psychiatrist and psychologist for the diagnosis and management of intellectual disability, autism spectrum disorders, and behavioral disorders.

Keywords:

giant cell astrocytoma

TSC1 gene

TSC2 gene

cortical tubers

subependymal hamartoma

tuberous sclerosis

epilepsy

Authors:

Mustafin R.N.

Bashkir State Medical University, Ufa, Russia

ORCID: 0000-0002-4091-382X

Received:

23.04.2025

Accepted:

10.11.2025

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References:

Robinson J, Uzun O, Loh NR, et al. The association of neurodevelopmental abnormalities, congenital heart and renal defects in a tuberous sclerosis complex patient cohort. BMC Med. 2022;20(1):123. https://doi.org/10.1186/s12916-022-02325-0
Wang S, Ma R, Gao C, et al. Unraveling the function of TSC1-TSC2 complex: implications for stem cell fate. Stem Cell Res Ther. 2025;16(1):38. https://doi.org/10.1186/s13287-025-04170-3
Jóźwiak J, Sontowska I, Płoski R. Frequency of TSC1 and TSC2 mutations in American, British, Polish and Taiwanese populations. Mol Med Rep. 2013;8(3):909-913. https://doi.org/10.3892/mmr.2013.1583
Sasongko TH, Ismail NF, Nik Abdul Malik NM, et al. Rapamycin and its analogues (rapalogs) for Tuberous Sclerosis Complex-associated tumors: a systematic review on non-randomized studies using meta-analysis. Orphanet J Rare Dis. 2015;10:95. https://doi.org/10.1186/s13023-015-0317-7
Portocarrero LKL, Quental KN, Samorano LP, et al. Tuberous sclerosis complex: review based on new diagnostic criteria. An Bras Dermatol. 2018;93(3):323-331. https://doi.org/10.1590/abd1806-4841.20186972
Mitchell RA, Mitchell M, Williams K. The autism spectrum disorder phenotype in children with tuberous sclerosis complex: A systematic review and meta-analysis. Dev Med Child Neurol. 2022;64(10):1214-1229. https://doi.org/10.1111/dmcn.15307
de Vries PJ, Wilde L, de Vries MC, et al. A clinical update on tuberous sclerosis complex-associated neuropsychiatric disorders (TAND). Am J Med Genet C Semin Med Genet. 2018;178(3):309-320. https://doi.org/10.1002/ajmg.c.31637
Vanclooster S, Bissell S, van Eeghen AM, et al. The research landscape of tuberous sclerosis complex-associated neuropsychiatric disorders (TAND)-a comprehensive scoping review. J Neurodev Disord. 2022;14(1):13. https://doi.org/10.1186/s11689-022-09423-3
de Vries PJ, Heunis TM, Vanclooster S, et al. International consensus recommendations for the identification and treatment of tuberous sclerosis complex-associated neuropsychiatric disorders (TAND). J Neurodev Disord. 2023;15(1):32. https://doi.org/10.1186/s11689-023-09500-1
Northrup H, Aronow ME, Bebin EM, et al. International Tuberous Sclerosis Complex Consensus Group. Updated International Tuberous Sclerosis Complex Diagnostic Criteria and Surveillance and Management Recommendations. Pediatr Neurol. 2021;123:50-66. https://doi.org/10.1016/j.pediatrneurol.2021.07.011
Saleem MD, Oussedik E, Picardo M, et al. Acquired disorders with hypopigmentation: A clinical approach to diagnosis and treatment. J Am Acad Dermatol. 2019;80(5):1233-1250.e10. https://doi.org/10.1016/j.jaad.2018.07.070
Li M, Zhou Y, Chen C, et al. Efficacy and safety of mTOR inhibitors (rapamycin and its analogues) for tuberous sclerosis complex: a meta-analysis. Orphanet J Rare Dis. 2019;14(1):39. https://doi.org/10.1186/s13023-019-1012-x
Liu M, Ye J, You X. An updated meta-analysis of effectiveness and safety of mTOR inhibitors in the management of tuberous sclerosis complex patients. Childs Nerv Syst. 2024;40(3):823-829. https://doi.org/10.1007/s00381-023-06200-y
Rendtorff ND, Bjerregaard B, Frödin M, et al. Danish Tuberous Sclerosis Group. Analysis of 65 tuberous sclerosis complex (TSC) patients by TSC2 DGGE, TSC1/TSC2 MLPA, and TSC1 long-range PCR sequencing, and report of 28 novel mutations. Hum Mutat. 2005;26(4):374-383. https://doi.org/10.1002/humu.20227
Rosset C, Vairo F, Bandeira IC, et al. Molecular analysis of TSC1 and TSC2 genes and phenotypic correlations in Brazilian families with tuberous sclerosis. PLoS One. 2017;12(10):e0185713. https://doi.org/10.1371/journal.pone.0185713
Au KS, Williams AT, Roach ES, et al. Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States. Genet Med. 2007;9(2):88-100. https://doi.org/10.1097/gim.0b013e31803068c7
Hung CC, Su YN, Chien SC, et al. Molecular and clinical analyses of 84 patients with tuberous sclerosis complex. BMC Med Genet. 2006;7:72. https://doi.org/10.1097/10.1186/1471-2350-7-72
Tyburczy ME, Dies KA, Glass J, et al. Mosaic and Intronic Mutations in TSC1/TSC2 Explain the Majority of TSC Patients with No Mutation Identified by Conventional Testing. PLoS Genet. 2015;11(11):e1005637. https://doi.org/10.1371/journal.pgen.1005637
Ali M, Girimaji SC, Markandaya M, et al. Mutation and polymorphism analysis of TSC1 and TSC2 genes in Indian patients with tuberous sclerosis complex. Acta Neurol Scand. 2005;111(1):54-63. https://doi.org/10.1111/j.1600-0404.2004.00366.x
Yang G, Shi ZN, Meng Y, et al. Phenotypic and genotypic characterization of Chinese children diagnosed with tuberous sclerosis complex. Clin Genet. 2017;91(5):764-768. https://doi.org/10.1111/cge.12920
Chen H, Lin X, Lian S, et al. Novel nonsense mutation of the TSC2 gene in a case of Tuberous Sclerosis Complex. Eur J Dermatol. 2016;26(3):295-296. https://doi.org/10.1684/ejd.2016.2735
Hoogeveen-Westerveld M, Wentink M, van den Heuvel D, et al. Functional assessment of variants in the TSC1 and TSC2 genes identified in individuals with Tuberous Sclerosis Complex. Hum Mutat. 2011;32(4):424-435. https://doi.org/10.1002/humu.21451
Dabora SL, Jozwiak S, Franz DN, et al. Mutational analysis in a cohort of 224 tuberous sclerosis patients indicates increased severity of TSC2, compared with TSC1, disease in multiple organs. Am J Hum Genet. 2001;68(1):64-80. https://doi.org/10.1086/316951
Ding Y, Wang J, Zhou S, et al. Genotype and Phenotype Analysis of Chinese Children With Tuberous Sclerosis Complex: A Pediatric Cohort Study. Front Genet. 2020;11:204. https://doi.org/10.3389/fgene.2020.00204
Reyna-Fabián ME, Hernández-Martínez NL, Velázquez-Aragón JA, et al. First comprehensive TSC1/TSC2 mutational analysis in Mexican patients with Tuberous Sclerosis Complex reveals numerous novel pathogenic variants. Sci Rep. 2020;10(1):6589. https://doi.org/10.1038/s41598-020-62759-5