Definition and research guide
This page combines a MeSH definition, publication statistics and selected research abstracts. It is a starting point for reading the literature, not a medical textbook or a systematic evidence review.
Content available: 4 complete abstracts (753 words), 10 references. Full article text is not stored or reproduced here; follow the PMID, DOI or PMC links to read the original sources and their access terms.
Definition
Autosomal dominant neurocutaneous syndrome classically characterized by mental retardation; epilepsy; and skin lesions (e.g., adenoma sebaceum and hypomelanotic macules). There is, however, considerable heterogeneity in the neurologic manifestations. It is also associated with cortical tuber and hamartomas formation throughout the body, especially the heart, kidneys, and eyes. Mutations in two loci TSC1 and TSC2 that encode hamartin and tuberin, respectively, are associated with the disease.
Definition: NLM Medical Subject Headings (MeSH) scope note (Public domain (U.S. National Library of Medicine); attribution requested). View the MeSH record.
Also known as: Sclerosis, Tuberous; Bourneville Disease; Bourneville Phakomatosis; Bourneville Syndrome; Syndrome, Bourneville; Bourneville's Disease; Bourneville's Syndrome; Syndrome, Bourneville's.
Where it fits in the MeSH classification
- Broader topics
- Hamartoma; Neoplasms, Multiple Primary; Neoplastic Syndromes, Hereditary; Malformations of Cortical Development, Group I; Neurocutaneous Syndromes; Heredodegenerative Disorders, Nervous System
Related concepts
Research landscape
PubMed indexes 7,249 records tagged with the MeSH heading “Tuberous Sclerosis” (counts retrieved 2026-10-29). 1,229 of them (17.0%) were published from 2020 onward, and the busiest period so far is through 1999 with 2,887 records.
Reviews account for 1,037 records (14.3%) and meta-analyses for 23. Randomized controlled trials number 42 (0.6%) as a share of all records on the topic. Randomized trials make up only a small share of this literature, so much of what is known comes from laboratory, observational or descriptive work.
Show the data
| Period | Records |
|---|---|
| through 1999 | 2,887 |
| 2000-2009 | 1,297 |
| 2010-2019 | 1,836 |
| 2020 onward | 1,229 |
Publication-type chart data
| Type | Records | Share |
|---|---|---|
| Reviews | 1,037 | 14.3% |
| Meta-analyses | 23 | 0.3% |
| Randomized controlled trials | 42 | 0.6% |
Method: PubMed query "Tuberous Sclerosis"[MeSH Terms] with publication-type and date filters, retrieved 2026-10-29.
Reading the evidence in rare and inherited diseases
Rare conditions are difficult to study: few patients means small studies, case reports and registries are common, and randomized trials are the exception. Small samples limit precision and can exaggerate effects, and cases reported in the literature may be the most severe or unusual. Evidence from many small studies is best read together. Check how patients were identified, how many were included and how long they were followed.
Evidence from open-access studies
These open-access studies come from PubMed’s best-match results for this heading (papers whose main topic it is), ranked here by citation count, with one recent addition. Each abstract is reproduced in full under its recorded open licence so that you can read the authors’ own words. They illustrate the literature; they are not a systematic summary of it. Citation counts measure attention, not reliability or clinical benefit.
| Study / authors | Year | Source label / design | Europe PMC citations | Licence / source |
|---|---|---|---|---|
| Perfect match: mTOR inhibitors and tuberous sclerosis complex | 2022 | Review article Design not recorded in structured metadata | 67 | cc by PMID 35246210 · DOI · PMC8895788 |
| TFEB drives mTORC1 hyperactivation and kidney disease in Tuberous Sclerosis Complex | 2024 | Research article Design not recorded in structured metadata | 53 | cc by PMID 38195686 · DOI · PMC10776564 |
| Renal Cell Carcinoma in Tuberous Sclerosis Complex | 2021 | Review article Design not recorded in structured metadata | 50 | cc by PMID 34680979 · DOI · PMC8535193 |
| NEAT1 Promotes Epileptogenesis in Tuberous Sclerosis Complex | 2026 | Research article Design not recorded in structured metadata | 2 | cc by PMID 41090516 · DOI · PMC12767121 |
Perfect match: mTOR inhibitors and tuberous sclerosis complex [1]
Abstract reading summary — source excerpts
- Opening excerpt
- Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome that presents with diverse and complex clinical features and involves multiple human systems.
- Closing excerpt
- Herein, we have summarized the current utilization of mTOR inhibitors in the treatment of TSC and focused on their efficacy and safety, in an attempt to provide a reference to guide the treatment of TSC.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (175 words)
Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome that presents with diverse and complex clinical features and involves multiple human systems. TSC-related neurological abnormalities and organ dysfunction greatly affect the quality of life and can even result in death in patients with TSC. It is widely accepted that most TSC-related clinical manifestations are associated with hyperactivation of the mammalian target of rapamycin (mTOR) pathway caused by loss‑of‑function mutations in TSC1 or TSC2. Remarkable progress in basic and translational research has led to encouraging clinical advances. Although mTOR inhibitors (rapamycin/everolimus) demonstrate great potential in TSC management, two major concerns hamper their generalized application. One is the frequent manifestation of adverse events, such as stomatitis, infections, and menstrual disorders; and the other is the poor response in certain patients. Thus, indicators are required to effectively predict the efficacy of mTOR inhibitors. Herein, we have summarized the current utilization of mTOR inhibitors in the treatment of TSC and focused on their efficacy and safety, in an attempt to provide a reference to guide the treatment of TSC.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 35246210 · DOI · PMC8895788
TFEB drives mTORC1 hyperactivation and kidney disease in Tuberous Sclerosis Complex [2]
Abstract reading summary — source excerpts
- Opening excerpt
- Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, leading to hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) and lesions in multiple organs including lung (lymphangioleiomyomatosis) and kidney (angiomyolipoma and renal cell carcinoma).
- Closing excerpt
- These results change the view of the mechanisms of mTORC1 hyperactivation in TSC and may lead to therapeutic avenues.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (159 words)
Tuberous Sclerosis Complex (TSC) is caused by TSC1 or TSC2 mutations, leading to hyperactivation of mechanistic target of rapamycin complex 1 (mTORC1) and lesions in multiple organs including lung (lymphangioleiomyomatosis) and kidney (angiomyolipoma and renal cell carcinoma). Previously, we found that TFEB is constitutively active in TSC. Here, we generated two mouse models of TSC in which kidney pathology is the primary phenotype. Knockout of TFEB rescues kidney pathology and overall survival, indicating that TFEB is the primary driver of renal disease in TSC. Importantly, increased mTORC1 activity in the TSC2 knockout kidneys is normalized by TFEB knockout. In TSC2-deficient cells, Rheb knockdown or Rapamycin treatment paradoxically increases TFEB phosphorylation at the mTORC1-sites and relocalizes TFEB from nucleus to cytoplasm. In mice, Rapamycin treatment normalizes lysosomal gene expression, similar to TFEB knockout, suggesting that Rapamycin's benefit in TSC is TFEB-dependent. These results change the view of the mechanisms of mTORC1 hyperactivation in TSC and may lead to therapeutic avenues.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 38195686 · DOI · PMC10776564
Renal Cell Carcinoma in Tuberous Sclerosis Complex [3]
Abstract reading summary — source excerpts
- Opening excerpt
- Tuberous sclerosis complex (TSC) is an autosomal dominant disorder in which renal manifestations are prominent.
- Closing excerpt
- Finally, recent work has identified molecular links between TSC and BHD-associated tumors, involving the TFEB/TFE3 transcription factors.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (221 words)
Tuberous sclerosis complex (TSC) is an autosomal dominant disorder in which renal manifestations are prominent. There are three major renal lesions in TSC: angiomyolipomas, cysts, and renal cell carcinoma (RCC). Major recent advances have revolutionized our understanding of TSC-associated RCC, including two series that together include more than 100 TSC-RCC cases, demonstrating a mean age at onset of about 36 years, tumors in children as young as 7, and a striking 2:1 female predominance. These series also provide the first detailed understanding of the pathologic features of these distinctive tumors, which include chromophobe-like features and eosinophilia, with some of the tumors unclassified. This pathologic heterogeneity is distinctive and reminiscent of the pathologic heterogeneity in Birt-Hogg-Dube-associated RCC, which also includes chromophobe-like tumors. Additional advances include the identification of sporadic counterpart tumors that carry somatic TSC1/TSC2/mTOR mutations. These include unclassified eosinophilic tumors, eosinophilic solid cystic RCC (ESC-RCC), and RCC with leiomyomatous stroma (RCCLMS). A variety of epithelial renal neoplasms have been identified both in patients with tuberous sclerosis complex (TSC) and in the nonsyndromic setting associated with somatic mutations in the TSC1 and TSC2 genes. Interestingly, whether tumors are related to a germline or somatic TSC1/2 mutation, these tumors often display similar morphologic and immunophenotypic features. Finally, recent work has identified molecular links between TSC and BHD-associated tumors, involving the TFEB/TFE3 transcription factors.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 34680979 · DOI · PMC8535193
NEAT1 Promotes Epileptogenesis in Tuberous Sclerosis Complex [4]
Abstract reading summary — source excerpts
- Opening excerpt
- The primary neurological manifestations of tuberous sclerosis complex (TSC) are intractable epilepsy and intellectual impairment.
- Closing excerpt
- This study provides new insights into the transcriptional regulation of TSC-related epilepsy, highlighting the therapeutic potential of NEAT1.
- Interpretation limits
- Verbatim excerpts from the authors’ abstract; the closing excerpt may describe a finding, limitation or recommendation. Design, population, effect size and uncertainty have not been independently extracted or appraised. Read the complete abstract and linked paper before interpreting the findings.
Read complete abstract (198 words)
The primary neurological manifestations of tuberous sclerosis complex (TSC) are intractable epilepsy and intellectual impairment. Current treatment outcomes remain limited. Investigating the role of the epigenetic long non-coding RNA NEAT1 in TSC-related epilepsy and cognition is essential. RNA sequencing analysis of clinical tissue samples revealed that NEAT1 is differentially expressed in epileptogenic versus non-epileptogenic tubers and enriched in the PI3K-AKT signaling pathway. To prove and further investigate the functional role suggested by the earlier transcriptomic and pathway enrichment analyses, NEAT1-overexpression and NEAT1-knockdown TSC2 conditional knockout (CKO) mouse models, as well as TSC2-KO cell models, are established. In vivo experiments demonstrated that NEAT1 knockdown reduced seizure frequency and improved spatial learning and working memory. Cellular analyses in TSC model further revealed that NEAT1 significantly regulates the PI3K/AKT/mTOR signaling pathway, neurotransmitter receptor balance, and outward potassium currents. Specifically, NEAT1 overexpression excessively activated the mTORC1 signaling, leading to changes in 4E-BP1 and S6K and abnormal cell proliferation. Moreover, NEAT1 overexpression contributed to an imbalance in excitatory neurotransmitter receptors and outward potassium currents, resulting in neuronal hyperexcitability, whereas NEAT1 knockdown has the opposite effect. This study provides new insights into the transcriptional regulation of TSC-related epilepsy, highlighting the therapeutic potential of NEAT1.
Abstract reproduced from the open-access article under the recorded cc by licence; © the authors. PMID 41090516 · DOI · PMC12767121
Key reviews and meta-analyses
The most cited review-type papers among PubMed’s best-match results for this heading, listed with bibliographic details only. Follow the links for the full text and access terms.
- Research article The tuberous sclerosis complex [5]
- Research article Tuberous sclerosis [6]
- Research article Tuberous sclerosis complex [7]
- Research article Neurological and neuropsychiatric aspects of tuberous sclerosis complex [8]
- Research article Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States [9]
- Research article The tuberous sclerosis complex [10]
References
- Luo C, Ye WR, Shi W, Yin P, Chen C, He YB, et al.. Perfect match: mTOR inhibitors and tuberous sclerosis complex. . 2022. PMID 35246210 · DOI · PMC8895788
- Alesi N, Khabibullin D, Rosenthal DM, Akl EW, Cory PM, Alchoueiry M, et al.. TFEB drives mTORC1 hyperactivation and kidney disease in Tuberous Sclerosis Complex. . 2024. PMID 38195686 · DOI · PMC10776564
- Henske EP, Cornejo KM, Wu CL. Renal Cell Carcinoma in Tuberous Sclerosis Complex. . 2021. PMID 34680979 · DOI · PMC8535193
- Kuang S, Liu T, Wei Z, Xu J, Han J, Wang J, et al.. NEAT1 Promotes Epileptogenesis in Tuberous Sclerosis Complex. . 2026. PMID 41090516 · DOI · PMC12767121
- Crino PB, Nathanson KL, Henske EP. The tuberous sclerosis complex. N Engl J Med. 2006. PMID 17005952 · DOI
- Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. Lancet. 2008. PMID 18722871 · DOI
- Henske EP, Jóźwiak S, Kingswood JC, Sampson JR, Thiele EA. Tuberous sclerosis complex. Nat Rev Dis Primers. 2016. PMID 27226234 · DOI
- Curatolo P, Moavero R, de Vries PJ. Neurological and neuropsychiatric aspects of tuberous sclerosis complex. Lancet Neurol. 2015. PMID 26067126 · DOI
- Au KS, Williams AT, Roach ES, Batchelor L, Sparagana SP, Delgado MR, et al.. Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States. Genet Med. 2007. PMID 17304050 · DOI
- Orlova KA, Crino PB. The tuberous sclerosis complex. Ann N Y Acad Sci. 2010. PMID 20146692 · DOI · PMC2892799
About this article
- Sources
- NLM Medical Subject Headings (definition, synonyms); NCBI PubMed (counts, identifiers); Europe PMC (open-access abstracts and citation counts).
- Verification
- Every reference was resolved against PubMed on 2026-10-31; title, year and DOI matched.
- Review state
- automated source verified; no human expert review has been recorded yet.
- Version
- 1, last updated 2026-10-29.
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Evidence strength
EvidenceHelix's computed view of the study designs behind this topic: how common meta-analyses, randomized trials and reviews are, how recent the literature is, and a plain-language reading. It describes the design mix of the literature. It is not a quality appraisal of any study, and it is not medical advice.