tuberous sclerosis

Summary

Summary: 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.

Top Publications

  1. Curatolo P, Jozwiak S, Nabbout R. Management of epilepsy associated with tuberous sclerosis complex (TSC): clinical recommendations. Eur J Paediatr Neurol. 2012;16:582-6 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is a leading genetic cause of epilepsy. TSC-associated epilepsy generally begins during the first year of life, and is associated with neurodevelopmental and cognitive problems...
  2. Hoogeveen Westerveld M, Ekong R, Povey S, Karbassi I, Batish S, den Dunnen J, et al. Functional assessment of TSC1 missense variants identified in individuals with tuberous sclerosis complex. Hum Mutat. 2012;33:476-9 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in the TSC1 or TSC2 genes...
  3. Harari S, Torre O, Moss J. Lymphangioleiomyomatosis: what do we know and what are we looking for?. Eur Respir Rev. 2011;20:34-44 pubmed publisher
    ..It affects predominantly females and can occur sporadically or in patients with tuberous sclerosis complex...
  4. van den Ouweland A, Elfferich P, Zonnenberg B, Arts W, Kleefstra T, Nellist M, et al. Characterisation of TSC1 promoter deletions in tuberous sclerosis complex patients. Eur J Hum Genet. 2011;19:157-63 pubmed publisher
    b>Tuberous sclerosis complex (TSC), an autosomal dominant disorder, is a multisystem disease with manifestations in the central nervous system, kidneys, skin and/or heart. Most TSC patients carry a pathogenic mutation in either TSC1 or TSC2...
  5. Feliciano D, Su T, Lopez J, Platel J, Bordey A. Single-cell Tsc1 knockout during corticogenesis generates tuber-like lesions and reduces seizure threshold in mice. J Clin Invest. 2011;121:1596-607 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by mutations in Tsc1 or Tsc2 that lead to mammalian target of rapamycin (mTOR) hyperactivity...
  6. Kocabas A, Ekici F, Cetin I, Emir S, Demir H, Arı M, et al. Cardiac rhabdomyomas associated with tuberous sclerosis complex in 11 children: presentation to outcome. Pediatr Hematol Oncol. 2013;30:71-9 pubmed publisher
    Cardiac rhabdomyomas (CRs) are the most common heart tumors in children and closely associated with tuberous sclerosis complex (TSC)...
  7. Krueger D, Care M, Holland K, Agricola K, Tudor C, Mangeshkar P, et al. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med. 2010;363:1801-11 pubmed publisher
    ..resection is the standard treatment for subependymal giant-cell astrocytomas in patients with the tuberous sclerosis complex...
  8. Zhou J, Shrikhande G, Xu J, McKay R, Burns D, Johnson J, et al. Tsc1 mutant neural stem/progenitor cells exhibit migration deficits and give rise to subependymal lesions in the lateral ventricle. Genes Dev. 2011;25:1595-600 pubmed publisher
    ..SENs) and subependymal giant cell astrocytomas (SEGAs) are common brain lesions found in patients with tuberous sclerosis complex (TSC)...
  9. Ehninger D, Silva A. Increased levels of anxiety-related behaviors in a Tsc2 dominant negative transgenic mouse model of tuberous sclerosis. Behav Genet. 2011;41:357-63 pubmed publisher
    b>Tuberous sclerosis (TSC) is a single-gene disorder caused by heterozygous mutations in the TSC1 or TSC2 gene. TSC is often associated with neurological (e.g...

More Information

Publications92

  1. Reith R, Way S, McKenna J, Haines K, Gambello M. Loss of the tuberous sclerosis complex protein tuberin causes Purkinje cell degeneration. Neurobiol Dis. 2011;43:113-22 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is a neurogenetic disorder that often causes brain abnormalities leading to epilepsy, developmental delay, and autism...
  2. Auricchio N, Malinowska I, SHAW R, Manning B, Kwiatkowski D. Therapeutic trial of metformin and bortezomib in a mouse model of tuberous sclerosis complex (TSC). PLoS ONE. 2012;7:e31900 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is a human genetic disorder in which loss of either TSC1 or TSC2 leads to development of hamartoma lesions, which can progress and be life-threatening or fatal...
  3. Li S, Yu S, Zhang C, Shu H, Liu S, An N, et al. Increased expression of matrix metalloproteinase 9 in cortical lesions from patients with focal cortical dysplasia type IIb and tuberous sclerosis complex. Brain Res. 2012;1453:46-55 pubmed publisher
    ..lesions in the cerebral cortex that are characteristic of focal cortical dysplasia type IIb (FCDIIb) and tuberous sclerosis complex (TSC) are well-recognized causes of chronic intractable epilepsy in children...
  4. Jozwiak S, Kotulska K, Domańska Pakieła D, Lojszczyk B, Syczewska M, Chmielewski D, et al. Antiepileptic treatment before the onset of seizures reduces epilepsy severity and risk of mental retardation in infants with tuberous sclerosis complex. Eur J Paediatr Neurol. 2011;15:424-31 pubmed publisher
    Epilepsy appears in 70-80% of patients with tuberous sclerosis complex, most commonly in the first year of age. Early manifestation of epilepsy is associated with drug-resistant epilepsy and mental retardation in more than 80% of patients...
  5. Torrelo A, Hadj Rabia S, Colmenero I, Piston R, Sybert V, Hilari Carbonell H, et al. Folliculocystic and collagen hamartoma of tuberous sclerosis complex. J Am Acad Dermatol. 2012;66:617-21 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is an autosomal dominant disorder characterized by tumors and hamartomas in several organs including the skin.
  6. Tillema J, Leach J, Krueger D, Franz D. Everolimus alters white matter diffusion in tuberous sclerosis complex. Neurology. 2012;78:526-31 pubmed publisher
    Diffusion tensor imaging (DTI) analysis was performed on patients with tuberous sclerosis complex (TSC) to investigate potential changes in normal-appearing white matter after treatment with everolimus, a mammalian target of rapamycin (..
  7. Peters J, Sahin M, Vogel Farley V, Jeste S, Nelson C, Gregas M, et al. Loss of white matter microstructural integrity is associated with adverse neurological outcome in tuberous sclerosis complex. Acad Radiol. 2012;19:17-25 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is a genetic neurocutaneous syndrome in which cognitive and social-behavioral outcomes for patients vary widely in an unpredictable manner. The cause of adverse neurologic outcome remains unclear...
  8. Khwaja O, Sahin M. Translational research: Rett syndrome and tuberous sclerosis complex. Curr Opin Pediatr. 2011;23:633-9 pubmed publisher
    ..Rett syndrome (RTT) and tuberous sclerosis complex (TSC) are both Mendelian disorders that present with autism, epilepsy, and intellectual disability, ..
  9. Bissler J, Kingswood J, Radzikowska E, Zonnenberg B, Frost M, Belousova E, et al. Everolimus for angiomyolipoma associated with tuberous sclerosis complex or sporadic lymphangioleiomyomatosis (EXIST-2): a multicentre, randomised, double-blind, placebo-controlled trial. Lancet. 2013;381:817-24 pubmed
    ..with constitutive activation of mammalian target of rapamycin (mTOR), and are common in patients with tuberous sclerosis complex and sporadic lymphangioleiomyomatosis...
  10. Anderl S, Freeland M, Kwiatkowski D, Goto J. Therapeutic value of prenatal rapamycin treatment in a mouse brain model of tuberous sclerosis complex. Hum Mol Genet. 2011;20:4597-604 pubmed publisher
    Epileptic seizures, particularly infantile spasms, are often seen in infants with tuberous sclerosis complex (TSC) soon after birth...
  11. Chopra M, Lawson J, Wilson M, Kennedy S, Taylor P, Buckley M, et al. An Australian tuberous sclerosis cohort: are surveillance guidelines being met?. J Paediatr Child Health. 2011;47:711-6 pubmed publisher
    This study aims to describe the phenotypic and genotypic characteristics of 45 Australian patients with tuberous sclerosis complex (TSC), to assess risk factors for intellectual disability, to compare patients with TSC1 and TSC2 mutations ..
  12. Dimitroff B, Howe K, Watson A, Campion B, Lee H, Zhao N, et al. Diet and energy-sensing inputs affect TorC1-mediated axon misrouting but not TorC2-directed synapse growth in a Drosophila model of tuberous sclerosis. PLoS ONE. 2012;7:e30722 pubmed publisher
    ..Hyperactivation of the TOR pathway by mutations in the upstream TOR inhibitors TSC1 (tuberous sclerosis complex 1) or TSC2 promotes benign tumors and neurological and behavioral deficits, a syndrome known as ..
  13. Wataya Kaneda M, Tanaka M, Nakamura A, Matsumoto S, Katayama I. A topical combination of rapamycin and tacrolimus for the treatment of angiofibroma due to tuberous sclerosis complex (TSC): a pilot study of nine Japanese patients with TSC of different disease severity. Br J Dermatol. 2011;165:912-6 pubmed publisher
    Dysregulation of mTOR signalling by mutations in tuberin and/or hamartin leads to the formation of tuberous sclerosis complex (TSC). Trials to treat TSC using mTOR inhibitors, including rapamycin, have been performed...
  14. Franz D, Belousova E, Sparagana S, Bebin E, Frost M, Kuperman R, et al. Efficacy and safety of everolimus for subependymal giant cell astrocytomas associated with tuberous sclerosis complex (EXIST-1): a multicentre, randomised, placebo-controlled phase 3 trial. Lancet. 2013;381:125-32 pubmed publisher
    b>Tuberous sclerosis complex is a genetic disorder leading to constitutive activation of mammalian target of rapamycin (mTOR) and growth of benign tumours in several organs...
  15. Feliciano D, Quon J, Su T, Taylor M, Bordey A. Postnatal neurogenesis generates heterotopias, olfactory micronodules and cortical infiltration following single-cell Tsc1 deletion. Hum Mol Genet. 2012;21:799-810 pubmed publisher
    Neurological symptoms in tuberous sclerosis complex (TSC) and associated brain lesions are thought to arise from abnormal embryonic neurogenesis due to inherited mutations in Tsc1 or Tsc2...
  16. Gomes A, Gomes Y, Lima F, Pessoa S. Multiple facial angiofibromas treated with high-frequency equipment. An Bras Dermatol. 2011;86:S186-9 pubmed
    b>Tuberous sclerosis is a rare genetic disease with autosomal dominant inheritance, associated with multiple hamartomas in several organs, such as the brain, skin, lung, kidney, heart and eyes...
  17. Araujo L, Lima L, Alvarenga T, Martelli Junior H, Coletta R, de Aquino S, et al. Oral and neurocutaneous phenotypes of familial tuberous sclerosis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2011;111:87-94 pubmed publisher
    The objective of this study was to describe the pattern of inheritance and the clinical features in a large family with tuberous sclerosis (TS), and to focus on the general diagnosis after the initial oral examination.
  18. Michelozzi C, Di Leo G, Galli F, Silva Barbosa F, Labriola F, Sardanelli F, et al. Subependymal nodules and giant cell tumours in tuberous sclerosis complex patients: prevalence on MRI in relation to gene mutation. Childs Nerv Syst. 2013;29:249-54 pubmed publisher
    ..the presence of subependymal nodules (SENs), subependymal giant cell tumours (SGCTs) and gene mutation in tuberous sclerosis complex (TSC) patients...
  19. Kassiri J, Snyder T, Bhargava R, Wheatley B, Sinclair D. Cortical tubers, cognition, and epilepsy in tuberous sclerosis. Pediatr Neurol. 2011;44:328-32 pubmed publisher
    b>Tuberous sclerosis complex is an autosomal-dominant genetic disorder characterized by hamartomatous growth in various organs. Patients who have this disorder exhibit a high rate of epilepsy and cognitive problems...
  20. Birca A, Mercier C, Major P. Rapamycin as an alternative to surgical treatment of subependymal giant cell astrocytomas in a patient with tuberous sclerosis complex. J Neurosurg Pediatr. 2010;6:381-4 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is associated with the potential development of benign hamartomas, including subependymal giant cell astrocytomas (SEGAs)...
  21. Yates J, MacLean C, Higgins J, Humphrey A, le Maréchal K, Clifford M, et al. The Tuberous Sclerosis 2000 Study: presentation, initial assessments and implications for diagnosis and management. Arch Dis Child. 2011;96:1020-5 pubmed publisher
    The Tuberous Sclerosis 2000 Study is the first comprehensive longitudinal study of tuberous sclerosis (TS) and aims to identify factors that determine prognosis. Mode of presentation and findings at initial assessments are reported here...
  22. Carson R, Van Nielen D, Winzenburger P, Ess K. Neuronal and glia abnormalities in Tsc1-deficient forebrain and partial rescue by rapamycin. Neurobiol Dis. 2012;45:369-80 pubmed publisher
    b>Tuberous Sclerosis Complex (TSC) is a multiorgan genetic disease that prominently features brain malformations (tubers) with many patients suffering from epilepsy and autism...
  23. Bateup H, Johnson C, Denefrio C, Saulnier J, Kornacker K, Sabatini B. Excitatory/inhibitory synaptic imbalance leads to hippocampal hyperexcitability in mouse models of tuberous sclerosis. Neuron. 2013;78:510-22 pubmed publisher
    ..Here, we examine the function of the tuberous sclerosis complex (TSC)-mTOR signaling pathway, a common target of mutations associated with epilepsy and autism ..
  24. Krueger D, Northrup H. Tuberous sclerosis complex surveillance and management: recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013;49:255-65 pubmed publisher
    b>Tuberous sclerosis complex is a genetic disorder affecting every organ system, but disease manifestations vary significantly among affected individuals...
  25. Zeng L, Rensing N, Zhang B, Gutmann D, Gambello M, Wong M. Tsc2 gene inactivation causes a more severe epilepsy phenotype than Tsc1 inactivation in a mouse model of tuberous sclerosis complex. Hum Mol Genet. 2011;20:445-54 pubmed publisher
    b>Tuberous Sclerosis Complex (TSC) is an autosomal dominant, multi-system disorder, typically involving severe neurological symptoms, such as epilepsy, cognitive deficits and autism...
  26. Trindade A, Medvetz D, Neuman N, Myachina F, Yu J, Priolo C, et al. MicroRNA-21 is induced by rapamycin in a model of tuberous sclerosis (TSC) and lymphangioleiomyomatosis (LAM). PLoS ONE. 2013;8:e60014 pubmed publisher
    ..Women with LAM can also develop renal angiomyolipomas. LAM is caused by mutations in the tuberous sclerosis complex genes (TSC1 or TSC2), resulting in hyperactive mammalian Target of Rapamycin (mTOR) signaling...
  27. Yasin S, Ali A, Tata M, Picker S, Anderson G, Latimer Bowman E, et al. mTOR-dependent abnormalities in autophagy characterize human malformations of cortical development: evidence from focal cortical dysplasia and tuberous sclerosis. Acta Neuropathol. 2013;126:207-18 pubmed publisher
    ..Similar pathological changes are seen in the cortical malformations that characterize patients with tuberous sclerosis complex (TSC)...
  28. Díaz Díaz D, Ibarrola C, Gómez Sanz R, Pérez Hurtado B, Salazar Tabares J, Colina Ruizdelgado F. Neuroendocrine tumor of the pancreas in a patient with tuberous sclerosis: a case report and review of the literature. Int J Surg Pathol. 2012;20:390-5 pubmed publisher
    A rare case of pancreatic neuroendocrine neoplasm in a patient with tuberous sclerosis complex is described...
  29. Larson A, Hedgire S, Deshpande V, Stemmer Rachamimov A, Harisinghani M, Ferrone C, et al. Pancreatic neuroendocrine tumors in patients with tuberous sclerosis complex. Clin Genet. 2012;82:558-63 pubmed publisher
    We explored pancreatic neuroendocrine tumors (PanNETs) associated with tuberous sclerosis complex (TSC) to determine their incidence in the TSC population; define their clinical, radiological, and pathological characteristics; and ..
  30. Franz D, WEISS B. Molecular therapies for tuberous sclerosis and neurofibromatosis. Curr Neurol Neurosci Rep. 2012;12:294-301 pubmed publisher
    Neurofibromatosis type 1 (NF1) and tuberous sclerosis complex (TSC) are autosomal-dominant genetic disorders that result from dysregulation of the PI3K/AKT/mammalian target of rapamycin (mTOR) pathway...
  31. Adriaensen M, Schaefer Prokop C, Duyndam D, Zonnenberg B, Prokop M. Radiological evidence of lymphangioleiomyomatosis in female and male patients with tuberous sclerosis complex. Clin Radiol. 2011;66:625-8 pubmed publisher
    To determine the gender-specific prevalence of pulmonary cysts typical for lymphangioleiomyomatosis (LAM) in adult patients with known tuberous sclerosis complex (TSC).
  32. Staehler M, Sauter M, Helck A, Linsenmaier U, Weber L, Mayer K, et al. Nephron-sparing resection of angiomyolipoma after sirolimus pretreatment in patients with tuberous sclerosis. Int Urol Nephrol. 2012;44:1657-61 pubmed publisher
    Renal angiomyolipoma in patients with tuberous sclerosis can cause life-threatening bleeding. Embolization or resection is recommended, but either intervention may result in substantial loss of renal function...
  33. Sato A, Kasai S, Kobayashi T, Takamatsu Y, Hino O, Ikeda K, et al. Rapamycin reverses impaired social interaction in mouse models of tuberous sclerosis complex. Nat Commun. 2012;3:1292 pubmed publisher
    ..Genetic disorders frequently accompany autism spectrum disorder, such as tuberous sclerosis complex caused by haploinsufficiency of the TSC1 and TSC2 genes...
  34. Aboian M, Wong Kisiel L, Rank M, Wetjen N, Wirrell E, Witte R. SISCOM in children with tuberous sclerosis complex-related epilepsy. Pediatr Neurol. 2011;45:83-8 pubmed publisher
    Identification of a single epileptogenic focus in patients with tuberous sclerosis complex is a challenge...
  35. Cohen J, Tham K, Mastrandrea N, Gallegos A, Monks T, Lau S. cAMP-dependent cytosolic mislocalization of p27(kip)-cyclin D1 during quinol-thioether-induced tuberous sclerosis renal cell carcinoma. Toxicol Sci. 2011;122:361-71 pubmed publisher
    The loss of tuberin, the tuberous sclerosis-2 (Tsc-2) gene product, is associated with cytoplasmic mislocalization of p27 in uterine leiomyomas derived from Eker rats (Tsc-2(EK/+)) and in human metastatic renal cell carcinoma tissue...
  36. Yuan E, Tsai P, Greene Colozzi E, Sahin M, Kwiatkowski D, Malinowska I. Graded loss of tuberin in an allelic series of brain models of TSC correlates with survival, and biochemical, histological and behavioral features. Hum Mol Genet. 2012;21:4286-300 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is a neurodevelopmental disorder with prominent brain manifestations due to mutations in either TSC1 or TSC2...
  37. Dabora S, Franz D, Ashwal S, Sagalowsky A, DiMario F, Miles D, et al. Multicenter phase 2 trial of sirolimus for tuberous sclerosis: kidney angiomyolipomas and other tumors regress and VEGF- D levels decrease. PLoS ONE. 2011;6:e23379 pubmed publisher
    b>Tuberous sclerosis (TSC) related tumors are characterized by constitutively activated mTOR signaling due to mutations in TSC1 or TSC2.
  38. Prabowo A, Anink J, Lammens M, Nellist M, van den Ouweland A, Adle Biassette H, et al. Fetal brain lesions in tuberous sclerosis complex: TORC1 activation and inflammation. Brain Pathol. 2013;23:45-59 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is an autosomal dominant disorder caused by mutations in either the TSC1 or TSC2 genes and characterized by developmental brain abnormalities...
  39. CHEVERE TORRES I, Maki J, Santini E, Klann E. Impaired social interactions and motor learning skills in tuberous sclerosis complex model mice expressing a dominant/negative form of tuberin. Neurobiol Dis. 2012;45:156-64 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is a genetic disorder characterized by the development of hamartomas in multiple organs...
  40. Jozwiak S, Nabbout R, Curatolo P. Management of subependymal giant cell astrocytoma (SEGA) associated with tuberous sclerosis complex (TSC): Clinical recommendations. Eur J Paediatr Neurol. 2013;17:348-52 pubmed publisher
    ..giant cell astrocytoma (SEGA) is a type of brain tumour that develops in 10-15% of individuals with tuberous sclerosis complex (TSC)...
  41. Gallagher A, Madan N, Stemmer Rachamimov A, Thiele E. Progressive calcified tuber in a young male with tuberous sclerosis complex. Dev Med Child Neurol. 2010;52:1062-5 pubmed publisher
    Tubers are the most common brain lesions in tuberous sclerosis complex (TSC), and typically remain stable in size and appearance...
  42. Ehninger D, Silva A. Rapamycin for treating Tuberous sclerosis and Autism spectrum disorders. Trends Mol Med. 2011;17:78-87 pubmed publisher
    b>Tuberous sclerosis (TSC) is a genetic disorder caused by heterozygous mutations in the TSC1 or TSC2 genes and is associated with autism spectrum disorders (ASD) in 20-60% of cases...
  43. Goto J, Talos D, Klein P, Qin W, Chekaluk Y, Anderl S, et al. Regulable neural progenitor-specific Tsc1 loss yields giant cells with organellar dysfunction in a model of tuberous sclerosis complex. Proc Natl Acad Sci U S A. 2011;108:E1070-9 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is a multiorgan genetic disease in which brain involvement causes epilepsy, intellectual disability, and autism...
  44. Rubí S, Costes N, Heckemann R, Bouvard S, Hammers A, Martí Fuster B, et al. Positron emission tomography with ?-[11C]methyl-L-tryptophan in tuberous sclerosis complex-related epilepsy. Epilepsia. 2013;54:2143-50 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is often associated with cerebral tubers and medically intractable epilepsy...
  45. CHEVERE TORRES I, Kaphzan H, Bhattacharya A, Kang A, Maki J, Gambello M, et al. Metabotropic glutamate receptor-dependent long-term depression is impaired due to elevated ERK signaling in the ?RG mouse model of tuberous sclerosis complex. Neurobiol Dis. 2012;45:1101-10 pubmed publisher
    b>Tuberous sclerosis complex (TSC) and fragile X syndrome (FXS) are caused by mutations in negative regulators of translation. FXS model mice exhibit enhanced metabotropic glutamate receptor-dependent long-term depression (mGluR-LTD)...
  46. Truchuelo T, Díaz Ley B, Rios L, Alcántara J, Jaen P. Facial angiofibromas treated with topical rapamycin: an excellent choice with fast response. Dermatol Online J. 2012;18:15 pubmed
    b>Tuberous sclerosis (TS) is the second most common genodermatosis in our country and one of its main characteristics is the presence of facial angiofibromas...
  47. Hoogeveen Westerveld M, Wentink M, van den Heuvel D, Mozaffari M, Ekong R, Povey S, et al. Functional assessment of variants in the TSC1 and TSC2 genes identified in individuals with Tuberous Sclerosis Complex. Hum Mutat. 2011;32:424-35 pubmed publisher
    ..to characterize variants identified in the TSC1 and TSC2 genes in individuals with, or suspected of having, Tuberous Sclerosis Complex (TSC). Here we present an overview of our functional studies on 45 TSC1 and 107 TSC2 variants...
  48. Neuman N, Henske E. Non-canonical functions of the tuberous sclerosis complex-Rheb signalling axis. EMBO Mol Med. 2011;3:189-200 pubmed publisher
    The protein products of the tuberous sclerosis complex (TSC) genes, TSC1 and TSC2, form a complex, which inhibits the small G-protein, Ras homolog enriched in brain (Rheb)...
  49. Tomasoni R, Mondino A. The tuberous sclerosis complex: balancing proliferation and survival. Biochem Soc Trans. 2011;39:466-71 pubmed publisher
    Mutations in genes encoding either hamartin [TSC1 (tuberous sclerosis complex 1)] or tuberin (TSC2) result in a multisystem disorder characterized by the development of benign tumours and hamartomas in several organs...
  50. Cusmai R, Moavero R, Bombardieri R, Vigevano F, Curatolo P. Long-term neurological outcome in children with early-onset epilepsy associated with tuberous sclerosis. Epilepsy Behav. 2011;22:735-9 pubmed publisher
    In tuberous sclerosis complex, early seizure onset is associated with high risk of intractable epilepsy and cognitive/behavioral impairment...
  51. Amin S, Carter M, Edwards R, Pople I, Aquilina K, Merrifield J, et al. The outcome of surgical management of subependymal giant cell astrocytoma in tuberous sclerosis complex. Eur J Paediatr Neurol. 2013;17:36-44 pubmed publisher
    ..The indications for surgery and outcomes of patients who underwent surgical removal of subependymal giant cell astrocytomas (SEGAs) in our institution between 2000 and 2011 were reviewed...
  52. Carson R, Fu C, Winzenburger P, Ess K. Deletion of Rictor in neural progenitor cells reveals contributions of mTORC2 signaling to tuberous sclerosis complex. Hum Mol Genet. 2013;22:140-52 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is a multisystem genetic disorder with severe neurologic manifestations, including epilepsy, autism, anxiety and attention deficit hyperactivity disorder...
  53. Benyounes N, Fohlen M, Devys J, Delalande O, Moures J, Cohen A. Cardiac rhabdomyomas in tuberous sclerosis patients: a case report and review of the literature. Arch Cardiovasc Dis. 2012;105:442-5 pubmed publisher
    Rhabdomyomas are the most common benign cardiac tumours. They are often associated with tuberous sclerosis and can be diagnosed antenatally and postnatally by echocardiography...
  54. Koenig M, Hebert A, Roberson J, Samuels J, SLOPIS J, Woerner A, et al. Topical rapamycin therapy to alleviate the cutaneous manifestations of tuberous sclerosis complex: a double-blind, randomized, controlled trial to evaluate the safety and efficacy of topically applied rapamycin. Drugs R D. 2012;12:121-6 pubmed publisher
    Facial angiofibromas are disfiguring facial lesions, present in up to 80% of patients with tuberous sclerosis complex...
  55. van Eeghen A, Nellist M, van Eeghen E, Thiele E. Central TSC2 missense mutations are associated with a reduced risk of infantile spasms. Epilepsy Res. 2013;103:83-7 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is an autosomal dominant syndrome with a variable neurocognitive phenotype...
  56. Lim G, Oliva E. The morphologic spectrum of uterine PEC-cell associated tumors in a patient with tuberous sclerosis. Int J Gynecol Pathol. 2011;30:121-8 pubmed publisher
    ..We report a 59-year-old woman with tuberous sclerosis, initially diagnosed with a uterine malignant mixed müllerian tumor, in whom the hysterectomy specimen also ..
  57. Kim S, Speirs C, Solnica Krezel L, Ess K. Zebrafish model of tuberous sclerosis complex reveals cell-autonomous and non-cell-autonomous functions of mutant tuberin. Dis Model Mech. 2011;4:255-67 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is an autosomal dominant disease caused by mutations in either the TSC1 (encodes hamartin) or TSC2 (encodes tuberin) genes...
  58. Grajkowska W, Kotulska K, Jurkiewicz E, Matyja E. Brain lesions in tuberous sclerosis complex. Review. Folia Neuropathol. 2010;48:139-49 pubmed
    b>Tuberous sclerosis complex (TSC) is an autosomal dominant, multisystem disease characterized by the development of multiple hamartomas and benign or rarely malignant neoplasms distributed at various sites throughout the body, especially ..
  59. Cabrera López C, Martí T, Catalá V, Torres F, Mateu S, Ballarín Castán J, et al. Effects of rapamycin on angiomyolipomas in patients with tuberous sclerosis. Nefrologia. 2011;31:292-8 pubmed publisher
    b>Tuberous sclerosis (TS) is a systemic disease, with an autosomal dominant pattern of inheritance caused by mutations in two genes (TSC1 and TSC2) that cause tumours (angiomyolipomas [AML], angiofibromas, astrocytomas)...
  60. Ryther R, Wong M. Mammalian target of rapamycin (mTOR) inhibition: potential for antiseizure, antiepileptogenic, and epileptostatic therapy. Curr Neurol Neurosci Rep. 2012;12:410-8 pubmed publisher
    ..mTOR inhibitors have antiepileptogenic and antiseizure effects in animal models of the genetic disease, tuberous sclerosis complex...
  61. Guo Y, Kwiatkowski D. Equivalent benefit of rapamycin and a potent mTOR ATP-competitive inhibitor, MLN0128 (INK128), in a mouse model of tuberous sclerosis. Mol Cancer Res. 2013;11:467-73 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is a hamartoma syndrome in which brain, renal, and lung tumors develop and cause both morbidity and death. Loss of either TSC1 or TSC2 in TSC hamartomas leads to activation of mTORC1...
  62. Hallett L, Foster T, Liu Z, Blieden M, Valentim J. Burden of disease and unmet needs in tuberous sclerosis complex with neurological manifestations: systematic review. Curr Med Res Opin. 2011;27:1571-83 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is a progressive genetic disorder characterized by pervasive benign tumor growth. We sought to assess the current understanding of burden of TSC-related neurological manifestations.
  63. Parkhitko A, Myachina F, Morrison T, Hindi K, Auricchio N, Karbowniczek M, et al. Tumorigenesis in tuberous sclerosis complex is autophagy and p62/sequestosome 1 (SQSTM1)-dependent. Proc Natl Acad Sci U S A. 2011;108:12455-60 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is a tumor suppressor syndrome characterized by benign tumors in multiple organs, including the brain and kidney...
  64. Curatolo P, Maria B. Tuberous sclerosis. Handb Clin Neurol. 2013;111:323-31 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is a genetic multisystem disorder characterized by widespread hamartomas in several organs, including the brain, heart, skin, eyes, kidney, lung, and liver...
  65. Northrup H, Krueger D. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 Iinternational Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013;49:243-54 pubmed publisher
    b>Tuberous sclerosis complex is highly variable in clinical presentation and findings. Disease manifestations continue to develop over the lifetime of an affected individual...
  66. Moavero R, Pinci M, Bombardieri R, Curatolo P. The management of subependymal giant cell tumors in tuberous sclerosis: a clinician's perspective. Childs Nerv Syst. 2011;27:1203-10 pubmed publisher
    b>Tuberous sclerosis (TSC) is a genetic multisystem disorder associated with hamartomas in several organs including subependymal giant cell tumors (SGCT)...
  67. Sun W, Zhu Y, Wang Z, Zhong Q, Gao F, Lou J, et al. Crystal structure of the yeast TSC1 core domain and implications for tuberous sclerosis pathological mutations. Nat Commun. 2013;4:2135 pubmed publisher
    b>Tuberous sclerosis complex is a disease caused by mutations in two tumor-suppressor genes, TSC1 and TSC2. The TSC1 protein, also known as hamartin, has a critical role in controlling mTOR signalling...
  68. Tsai P, Sahin M. Mechanisms of neurocognitive dysfunction and therapeutic considerations in tuberous sclerosis complex. Curr Opin Neurol. 2011;24:106-13 pubmed publisher
    ..b>Tuberous sclerosis complex (TSC) is a genetic disease that presents with epilepsy, autism, and intellectual disability...
  69. Budde K, Gaedeke J. Tuberous sclerosis complex-associated angiomyolipomas: focus on mTOR inhibition. Am J Kidney Dis. 2012;59:276-83 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is an autosomal dominant disorder promoting the development of benign tumors in multiple organ systems, including the skin, brain, and kidneys...
  70. Talos D, Sun H, Kosaras B, Joseph A, Folkerth R, Poduri A, et al. Altered inhibition in tuberous sclerosis and type IIb cortical dysplasia. Ann Neurol. 2012;71:539-51 pubmed publisher
    The most common neurological symptom of tuberous sclerosis complex (TSC) and focal cortical dysplasia (FCD) is early life refractory epilepsy...
  71. Sun P, Kohrman M, Liu J, Guo A, Rogerio J, Krueger D. Outcomes of resecting subependymal giant cell astrocytoma (SEGA) among patients with SEGA-related tuberous sclerosis complex: a national claims database analysis. Curr Med Res Opin. 2012;28:657-63 pubmed publisher
    To examine the outcomes following resection of subependymal giant cell astrocytoma (SEGA) among patients with SEGA-associated tuberous sclerosis complex (TSC).
  72. Lodish M, Stratakis C. Endocrine tumours in neurofibromatosis type 1, tuberous sclerosis and related syndromes. Best Pract Res Clin Endocrinol Metab. 2010;24:439-49 pubmed publisher
    Neurofibromatosis type 1 (NF-1) and tuberous sclerosis complex (TSC) are two familial syndromes known as phakomatoses that may be associated with endocrine tumours...
  73. Crino P. Evolving neurobiology of tuberous sclerosis complex. Acta Neuropathol. 2013;125:317-32 pubmed publisher
    Over the past decade, there have been numerous advances in our understanding of the molecular pathogenesis of tuberous sclerosis complex (TSC)...
  74. Borkowska J, Schwartz R, Kotulska K, Jozwiak S. Tuberous sclerosis complex: tumors and tumorigenesis. Int J Dermatol. 2011;50:13-20 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is an inherited disorder characterized by hamartomas in different body organs, mainly in the brain, skin, kidney, liver, lung, and heart...
  75. Kotulska K, Chmielewski D, Borkowska J, Jurkiewicz E, Kuczyński D, Kmiec T, et al. Long-term effect of everolimus on epilepsy and growth in children under 3 years of age treated for subependymal giant cell astrocytoma associated with tuberous sclerosis complex. Eur J Paediatr Neurol. 2013;17:479-85 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is a genetic disorder characterized by increased mammalian target of rapamycin (mTOR) activation and growth of benign tumors in several organs throughout the body...
  76. Micozkadioglu H, Koc Z, Ozelsancak R, Yildiz I. Rapamycin therapy for renal, brain, and skin lesions in a tuberous sclerosis patient. Ren Fail. 2010;32:1233-6 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is an inherited multisystem disorder; it may involve kidney, brain, skin, lungs, and liver. We report a 37-year-old female TSC patient presenting with skin lesions (angiofibromas, molluscum pendulum)...
  77. Shelton J, Ramakrishnaiah R, Glasier C, Phillips P. Cavernous sinus syndrome from an internal carotid artery aneurysm in an infant with tuberous sclerosis. J AAPOS. 2011;15:389-91 pubmed publisher
    Aneurysms are associated with tuberous sclerosis complex. We describe the first case of cavernous sinus syndrome from an intracavernous internal carotid artery aneurysm in a 9-month-old boy with tuberous sclerosis...
  78. Perek Polnik M, Jozwiak S, Jurkiewicz E, Perek D, Kotulska K. Effective everolimus treatment of inoperable, life-threatening subependymal giant cell astrocytoma and intractable epilepsy in a patient with tuberous sclerosis complex. Eur J Paediatr Neurol. 2012;16:83-5 pubmed publisher
    ..successful everolimus treatment of a huge subependymal giant cell astrocytoma in a 10-year old boy with tuberous sclerosis complex. The patient underwent several partial tumor resections complicated by intraoperative cardiac arrest...
  79. Humphrey A, MacLean C, Ploubidis G, Granader Y, Clifford M, Haslop M, et al. Intellectual development before and after the onset of infantile spasms: a controlled prospective longitudinal study in tuberous sclerosis. Epilepsia. 2014;55:108-16 pubmed publisher
    ..We tested the hypothesis in a longitudinal study of children with tuberous sclerosis (TS), who have a high risk of developing IS.
  80. Numis A, Major P, Montenegro M, Muzykewicz D, Pulsifer M, Thiele E. Identification of risk factors for autism spectrum disorders in tuberous sclerosis complex. Neurology. 2011;76:981-7 pubmed publisher
    ..of this study was to assess the prevalence of and to identify epidemiologic, genetic, electrophysiologic, and neuroanatomic risk factors for autism spectrum disorders (ASD) in a cohort of patients with tuberous sclerosis complex (TSC).
  81. Atalay S, Aypar E, Ucar T, Altug N, Deda G, Teber S, et al. Fetal and neonatal cardiac rhabdomyomas: clinical presentation, outcome and association with tuberous sclerosis complex. Turk J Pediatr. 2010;52:481-7 pubmed
    ..Cardiac rhabdomyomas (CRs) have a natural history of spontaneous regression and are closely associated with tuberous sclerosis complex (TSC)...
  82. Tiberio D, Franz D, Phillips J. Regression of a cardiac rhabdomyoma in a patient receiving everolimus. Pediatrics. 2011;127:e1335-7 pubmed publisher
    b>Tuberous sclerosis complex (TSC) is an autosomal dominant neurocutaneous disorder that can affect every organ of the body, most commonly the brain, kidneys, heart, and lungs...
  83. Waltereit R, Japs B, Schneider M, de Vries P, Bartsch D. Epilepsy and Tsc2 haploinsufficiency lead to autistic-like social deficit behaviors in rats. Behav Genet. 2011;41:364-72 pubmed publisher
    ..The monogenic disorder Tuberous Sclerosis Complex (TSC) has high rates of ASD, epilepsy and cognitive deficits...