...so what is tuberous sclerosis complex?
This webpage was produced as an assignment for Genetics 564, an undergraduate capstone course at the University of Wisconsin-Madison.
Tuberous sclerosis complex (TSC) is a genetic disorder that results in the formation of benign (non-cancerous) tumors in various organs, including the brain, kidneys, heart, lungs, eyes, and skin. These tumors, which often look like tubers---hence "tuberous" sclerosis complex, are non-cancerous because they are unable to invade other tissues or to metastasize .
Despite this, they may still have severe consequences if the growths disrupt the function of vital organs. TSC is one of the few known genetic causes for autism spectrum disorder, as well as epilepsy . It can also increase vulnerability to cancerous tumors such as renal cell carcinoma (kidney cancer) .
Above: A brief informational video about TSC by Novartis
How does it work?
TSC belongs to a family of hamartoma (benign tumor) and hypertrophic (excessive growth) syndromes. These disorders are caused by dysfunction in molecules/regulatory events that are directly involved in mTOR signaling . TSC, in particular, causes mTOR hyperactivity . For more information on how mTOR and TSC are related, see the tuberin page.
How do you get TSC?
What are the signs of TSC?
Not pictured: Hypomelanotic macules (skin), Shagreen patch (skin), or Nontraumatic ungual or periungual fibroma (nails) .
In addition to the major features presented above, minor features include: multiple, randomly distributed pits in dental enamel, hamartomatous rectal polyps, bone cysts, cerebral white matter radial migration lines, gingival fibromas, nonrenal hamartoma, retinal achromic patch, 'confetti' skin lesions, and multiple renal cysts .
A definite diagnosis of TSC includes two major features or one major feature and two minor features, while a probable diagnosis can be made with one major and one minor feature, and a possible diagnosis consists of one major or two minor features .
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 Davis, P. E., Peters, J. M., Krueger, D. A., & Sahin, M. (2015). Tuberous Sclerosis: A New Frontier in Targeted Treatment of Autism. Neurotherapeutics, 12(3), 572–583. http://doi.org/10.1007/s13311-015-0359-5
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 Inoki, K., Corradetti, M. N., Guan, K. (2005). Dysregulation of the TSC-mTOR pathway in human disease. Nature Genetics 37, 19-24. http://doi.org/10.1038/ng1494
 Roach, E.S., Gomez, Manuel, R., Northup, H. (1998). Tuberous Sclerosis Complex Consensus Conference: Revised Clinical Diagnostic Criteria. Journal of Child Neurology, 13(12) 624-628. http://doi.org/10.1177/088307389801301206
 Kwiatkowski, D. J., Palmer, M. R., Jozwiak, S., Bissler, J., et al. (2015). Response to everolimus is seen in TSC-associated SEGAs and angiomyolipomas independent of mutation type and site in TSC1 and TSC2. European Journal of Human Genetics 23, 1665–1672. http://doi.org/10.1038/ejhg.2015.47
 Qin, W., Kozlowski, P., Taillon, B.E. et al. (2010). Ultra deep sequencing detects a low rate of mosaic mutations in tuberous sclerosis complex. Human Genetics, 127(5), 573-582. http://doi.org/10.1007/s00439-010-0801-z
 Tyburczy M. E., Dies K. A., Glass J., Camposano S., Chekaluk Y., et al. (2015) Mosaic and Intronic Mutations in TSC1/TSC2 Explain the Majority of TSC Patients with No Mutation Identified by Conventional Testing. PLOS Genetics 11(11): e1005637. http://doi.org/10.1371/journal.pgen.1005637
 Giannikou K., Malinowska I. A., Pugh T. J., Yan R., Tseng Y. Y., et al. (2016). Whole Exome Sequencing Identifies TSC1/TSC2 Biallelic Loss as the Primary and Sufficient Driver Event for Renal Angiomyolipoma Development. PLOS Genetics 12(8): e1006242. http://doi.org/0.1371/journal.pgen.1006242
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 Foulkes, W. D., & Real, F. X. (2013). Many mosaic mutations. Current Oncology, 20(2), 85–87. http://doi.org/10.3747/co.20.1449
Dr. House: http://www.housemd-guide.com/timeline-ep.php
Fig 1: http://www.lsi.umich.edu/inoki-lab/inoki-lab-research, 
Fig 3: http://ib.bioninja.com.au/standard-level/topic-3-genetics/34-inheritance/mosaicism.html
Fig 4: https://en.wikipedia.org/wiki/Everolimus
Forehead plaque: http://www.medicinenet.com/image-collection/tuberous_sclerosis_fibrous_plaque_picture/picture.htm
Retinal Nodular hamartoma: http://flylib.com/books/en/3.283.1.13/1/
Cortical tuber: http://frontalcortex.com/?page=oll&topic=24&qid=479
Cardiac Rhabdomyoma: http://neuropathology-web.org/chapter7/images7/7-ts-heartmicro.jpg
Renal angiomyolipoma: http://www.webpathology.com/image.asp?case=71&n=5
Nontraumatic ungual/periungual fibroma: