Medscape is available in 5 Language Editions – Choose your Edition here.


Tuberous Sclerosis

  • Author: David Neal Franz, MD; Chief Editor: Amy Kao, MD  more...
Updated: Oct 14, 2015

Practice Essentials

Tuberous sclerosis complex (TSC) is a genetic disorder affecting cellular differentiation, proliferation, and migration early in development, resulting in a variety of hamartomatous lesions that may affect virtually every organ system of the body.

The best-known cutaneous manifestation of TSC is adenoma sebaceum, which often does not appear until late childhood or early adolescence. This lesion is an angiofibroma (ie, cutaneous hamartoma) and is not related to excessive sebum or acne. Flat, reddish macular lesions develop first, which can be mistaken for freckles early on. See the image below.

Facial angiofibromas in a young man with tuberous Facial angiofibromas in a young man with tuberous sclerosis complex.

Signs and symptoms

Findings in TSC include the following:

  • Neurologic findings: Abnormal neurologic findings result from the location, size, and growth of tubers and the presence of subependymal nodules (SENs) and subependymal giant cell astrocytomas (SEGAs)
  • Cutaneous findings: The best-known cutaneous manifestation of TSC is adenoma sebaceum, which often does not appear until late childhood or early adolescence
  • Cardiac findings: Cardiac involvement is usually maximal at birth or early in life; it may be the presenting sign of TSC, particularly in early infancy; 50-60% of individuals with TSC have evidence of cardiac disease, mostly rhabdomyomas.
  • Ophthalmic findings: At least 50% of patients have ocular abnormalities; some studies have reported a prevalence as high as 80%; these lesions are actually retinal astrocytomas that tend to become calcified over time
  • Pulmonary findings: Prospective and retrospective studies have found cystic pulmonary abnormalities in as many as 40% of women with TSC
  • Renal findings: Renal manifestations of TSC are the second most common clinical feature; 4 types of lesions can occur: autosomal dominant polycystic kidney disease lesions, isolated renal cyst(s), angiomyolipomas (AMLs), and renal cell carcinomas
  • Dental findings: Pitting of the dental enamel is invariably present in the permanent teeth of patients with TSC [1] ; gingival fibromas occur in 70% of adults with TSC, in 50% of children with mixed dentition (primary and permanent teeth), and in 3% of children with only primary teeth
  • Gastrointestinal findings: Hamartomas and polyposis of the stomach, intestine, and colon may occur
  • Hepatic findings: Hepatic cysts and hepatic AMLs, typically asymptomatic and nonprogressive, have been reported in as many as 24% of patients with TSC, with a marked female predominance (female-to-male ratio 5:1)
  • Skeletal findings: Sclerotic and hypertrophic lesions of bone may be found incidentally on radiography performed for other indications

See Clinical Presentation for more detail.


Laboratory studies

Laboratory studies are performed as indicated clinically to identify genetic mutations associated with TSC, monitor anticonvulsant treatment, identify idiosyncratic or dose-related adverse effects, and identify or monitor underlying renal or pulmonary disease. Diagnosis should be possible in most cases using established clinical criteria. Molecular genetic testing is useful in uncertain or questionable cases, as well as for prenatal diagnosis and for screening family members of an affected individual.

Imaging studies

The following 3 imaging studies are usually undertaken in patients with TSC:

  • Computed tomography scanning or magnetic resonance imaging of the brain: Performed to identify SEGAs before obstructive hydrocephalus occurs; they also identify the extent and number of cortical tubers present [2]
  • Renal ultrasonography: Performed to assess change in AMLs or cysts, in the hope that this will allow operative intervention prior to the development of renal failure
  • Echocardiography: Performed as part of the baseline evaluation in a patient with newly diagnosed or suspected TSC

Additional tests

Other tests used in the assessment of patients with TSC include the following:

  • Electroencephalography: Should be performed in patients with TSC in whom seizures are suspected; follow-up electroencephalography is performed as clinically indicated
  • Electrocardiography: Baseline electrocardiography is recommended for all patients newly diagnosed with TSC, since cardiac arrhythmias, although rare, may have sudden death as their presenting symptom

See Workup for more detail.


Pharmacologic treatment

Antiepileptic medications (AEDs) are the mainstay of therapy for patients with TSC. The choice of specific AED(s) for treating seizures in patients with TSC is based on the patient's seizure type(s), epilepsy syndrome(s), other involved organ systems, and age, along with AED side-effect profiles and available formulations.

The drug everolimus (Afinitor) helped to reduce kidney tumors linked to tuberous sclerosis complex (TSC) in a double-blind, placebo-controlled, phase-3 trial. The efficacy of the drug, which has been approved for use against TSC in the United States and Europe, was measured by the proportion of patients (diagnosed with tuberous sclerosis or sporadic lymphangioleiomyomatosis) in whom target angiolipomas were reduced by at least half of their total volume relative to baseline.[3, 4]

In the study, 118 patients (median age 31) from 24 centers in 11 countries received either everolimus (n=79) or placebo (n=39). Angiomyolipomas had a 42% response rate to everolimus and a 0% response rate to placebo.


Surgical treatment of patients with TSC can include the following:

  • Focal cortical resection
  • Corpus callosotomy
  • Vagus nerve stimulation

In addition, SEGAs require resection if they produce hydrocephalus or significant mass effect. If a gross total resection can be achieved, recurrence is unlikely.

See Treatment and Medication for more detail.



In 1880, Bourneville first described the cerebral manifestations of this disorder, applying the term "sclerose tubereuse" to indicate the superficial resemblance of the lesions to a potato. In 1908 Vogt set forth the triad of intractable epilepsy, mental retardation, and adenoma sebaceum; this description (until relatively recently) represented the hallmark of tuberous sclerosis complex (TSC) to most clinicians. Unfortunately, this concept led many primary care physicians and even neurologists to conclude, incorrectly, that a diagnosis of TSC predestines a child to crippling, lifelong neurological and psychological morbidity.

TSC is now known to be a genetic disorder affecting cellular differentiation, proliferation, and migration early in development, resulting in a variety of hamartomatous lesions that may affect virtually every organ system of the body. Less than one third of affected persons fit the classic constellation of symptoms.



Clinically, TSC exhibits an autosomal dominant inheritance pattern, with a high spontaneous mutation rate. Two distinct genetic loci responsible for TSC have been identified: one on chromosome band 9q34 (also referred to as TSC1) and another on chromosome band 16p13 (TSC2).

The TSC2 gene was identified in 1993, and its protein product has been named tuberin. Tuberin has GTPase-activating properties and seems to function as a tumor suppressor. The highest levels of tuberin are found in adult human brain, heart, and kidney; tuberin also has been localized to arterioles of kidney, skin, and heart, as well as to pyramidal neurons and cerebellar Purkinje cells. Its exact function, particularly during neurogenesis, remains unknown. Individual tubers are thought to arise developmentally when mutated neural progenitor cells in the subependymal germinal matrix give rise to abnormally migrating daughter cells that in turn produce tubers. The tubers may undergo cystic degeneration or calcification, or exhibit contrast enhancement on neuroimaging, but these features do not necessarily imply malignant transformation.

Hamartin, the TSC1 product, was identified in 1997 and may also function as a tumor suppressor. Rather than having completely separate functions, both hamartin and tuberin have been shown to have "coiled-coil" domains that interact with each other.[5] Hamartin and tuberin together form a tumor suppressor complex, which, through the GTPase activating function of tuberin, drives the small GTPase (termed Ras, homolog enhanced in brain) or Rheb into the inactive GDP-bound state. Rheb in the GTP-bound, active state is a positive effector of mTOR[6] (mTOR, ammalian arget f r apamycin—so named because of its ability to bind to the immunosuppressant drug rapamycin [sirolimus, Rapamune] before its function was known) (see following image).

Mammalian target of rapamycin (mTOR) activates the Mammalian target of rapamycin (mTOR) activates the protein S6 kinase, which enhances cell growth and protein synthesis. It, in turn, is regulated by multiple factors, including insulin, amino acids, the drugs rapamycin and its congeners (eg, RAD001), and the TSC gene products via the GTPase-activating protein Rheb.

mTOR, a major effector of cell growth (as opposed to cell proliferation) functions, among other things, as a sort of master switch for cellular anabolism versus catabolism, and it has important regulatory functions for cell volume and protein synthesis. It is also regulated by a wide variety of other factors, including insulin and amino acids. mTOR is a highly conserved protein kinase in evolution and is present in a wide range of organisms, from yeast, to Drosophila, to mammals.

Mutations in either hamartin or tuberin drive Rheb into the GTP-bound state, which results in constitutive mTOR signaling. mTOR appears to mediate many of its effects on cell growth through the phosphorylation of the ribosomal protein S6 kinases (S6Ks) and the repressors of protein synthesis initiation factor eIF4E, the 4EBPs. The S6Ks act to increase cell growth and protein synthesis, whereas the 4EBPs serve to inhibit these processes. mTOR interacts with the S6Ks and the 4EBPs through an associated protein, Raptor. When mTOR is constitutively activated through mutations in either hamartin or tuberin this results in the hamartomatous lesions of tuberous sclerosis in the brain, kidneys, heart, lungs, and other organs.

Rapamycin is capable of inducing regression of renal angiomyolipomas in animal models of TSC, and this effect appears to be enhanced by interferon-gamma, whose receptors are up-regulated by overactivity of mTOR. This pathway may be excessively active in other human malignancies as well as in TSC. These observations raise the possibility of new therapeutic interventions for this disorder. Trials of rapamycin for renal angiomyolipomas in humans with TSC have been completed (see Treatment section). Multicenter, randomized, placebo-controlled studies investigating RAD001 (everolimus) in the treatment of angiomyolipomatas (AMLs) and subependymal giant cell astrocytomas (SEGAs) are currently underway. On November 1, 2010, everolimus was approved by the US Food and Drug Administration (FDA) for SEGAs associated with tuberous sclerosis that cannot be treated with surgery.

The high incidence of sporadic TSC, coupled with a probable "second hit" phenomenon, seems a likely explanation for the marked phenotypic variability observed. The second hit hypothesis suggests that in addition to an inherited or sporadic autosomal mutation in one allele of either TSC 1 or TSC 2, clinical signs and/or symptoms manifest only after a further mutation or inactivating event in the second, unaffected allele (“second hit”). This allows considerable potential for diversity, not only among various deletions and mutations between 2 genetic loci, but also with regard to possible interactions between protein products of varying functionality arising from different mutations on each allele. Thereby adjacent tubers, angiomyolipomas, even facial angiofibromas can have different second hits and different genotypes within the same organ of the same patient.

Further complicating the high spontaneous mutation rate is the observation that parents of an affected child, who themselves show no sign of TSC, nonetheless have an increased risk (approximately 2% overall) of having additional affected children. This is thought to result from parental mosaicism for one of the TSC genes limited to cells of their germ line (ie, gonadal tissues). True failure of penetrance of the TSC genes is believed to be rare.

Recent research has identified phenotypic differences as they may relate to particular genotypes. Linkage studies initially suggested a roughly equal distribution of TSC1 and TSC2 mutations among affected individuals. However, subsequent mutational analysis has shown TSC2 mutations to be present in 80-90% of affected individuals, while TSC1 mutations are present in 10-20%. The TSC2 gene is contiguous with the gene producing polycystic kidney disease (PKD1). Individuals with features of both TSC and polycystic kidney disease (as opposed to simple renal cysts) likely have deletions spanning both genes.

Jones et al found a higher incidence of "mental handicap" in persons with TSC2 mutations than in those with TSC1 mutations. They identified mental handicap retrospectively in relatively broad terms: developmental quotient less than 70, inability to attend regular school without supplementary assistance, institutionalization, requiring assistance with daily activities, etc.

Dabora et al recently described genotypic and phenotypic features in 224 persons with TSC.[7] A TSC2 genetic abnormality was found to be associated consistently with more severe clinical disease regardless of organ system. Although prominent phenotypic variability was still the rule, patients with TSC2 abnormalities were more apt to have higher tuber counts, refractory seizures, autism, larger AML and/or cardiac rhabdomyomata, and more severe cutaneous lesions. This suggests that, while tuberin and hamartin have similar functions, tuberin plays a more critical role in regulation of cellular differentiation. While TSC2 mutations are more apt to be associated with severe clinical phenotypes, they predominate in all forms of the disease, mild and severe, familial and sporadic. Spontaneous mutations are also much more likely to reflect TSC2 disease. Suggestions that TSC1 disease is more likely familial than sporadic appear to be incorrect.




Birth incidence is 1 case per 6,000 population, with a prevalence of 1 case per 10,000 population.

Factors that hamper accurate assessment of incidence and prevalence include under-recognition of less severe phenotypes, high spontaneous mutation rate (approximately two thirds), marked variability of symptoms (even within specific kindreds of affected individuals), and reluctance of asymptomatic parents and relatives to undergo diagnostic testing related to concerns of uninsurability and social stigma.


Complications of neurological involvement are the most common causes of mortality and morbidity. These are due chiefly to intractable epilepsy, status epilepticus, and subependymal giant cell astrocytoma (SEGA) with associated hydrocephalus.

Renal complications are the next most frequent cause of morbidity and death. These usually arise from an enlarging AML, resulting in retroperitoneal hemorrhage. End-stage renal disease can occur, as a result of either destruction of normal renal parenchyma by an enlarging AML or polycystic kidney disease.

Less common are cardiac arrhythmias (which can present with sudden, unexplained death), congestive heart failure, and end-stage lung disease. Cardiac involvement is maximal in infants and exhibits spontaneous regression as the child grows older. Pulmonary disease occurs predominantly in women in the third and fourth decades of life.

Race-, sex-, and age-related statistics

TSC affects all races without a clear-cut predominance.

TSC affects both sexes equally. Some studies have suggested that males are more likely to suffer neurological morbidity, but this has not been demonstrated conclusively.

TSC can present at any age. In infants and children, it usually is identified as a cause of epilepsy, autism, or cardiac failure.

Older persons[8] may present with renal failure or pulmonary or cutaneous manifestations in the absence of prominent, or any, neurological symptoms.

Various organ systems are affected maximally at different points in life.

  • Cardiac involvement occurs during the intrauterine or neonatal period.
  • Rhabdomyomas tend to regress over time.
  • Epilepsy, autism, and developmental delays manifest themselves from infancy to adolescence.
  • Polycystic kidney disease usually is apparent in infancy or early childhood.
  • AMLs may develop at any time from childhood into adult life.
  • Lymphangiomyomatosis typically presents in the third or fourth decade of life.
Contributor Information and Disclosures

David Neal Franz, MD Professor of Pediatrics and Neurology, University of Cincinnati College of Medicine; Director, Tuberous Sclerosis Clinic, Cincinnati Children's Hospital Medical Center

David Neal Franz, MD is a member of the following medical societies: American Academy of Neurology, American Medical Association, Ohio State Medical Association, Children's Oncology Group, American Academy of Pediatrics, Child Neurology Society

Disclosure: Nothing to disclose.


Cameron W Thomas, MD, MS Assistant Professor of Pediatrics and Neurology, Department of Neurology, Cincinnati Children's Hospital Medical Center

Cameron W Thomas, MD, MS is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Kenneth J Mack, MD, PhD Senior Associate Consultant, Department of Child and Adolescent Neurology, Mayo Clinic

Kenneth J Mack, MD, PhD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, Phi Beta Kappa, Society for Neuroscience

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Have stock from Cellectar Biosciences; have stock from Varian medical systems; have stock from Express Scripts.

Additional Contributors

Robert J Baumann, MD Professor of Neurology and Pediatrics, Department of Neurology, University of Kentucky College of Medicine

Robert J Baumann, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, Child Neurology Society

Disclosure: Nothing to disclose.


The authors and editors of Medscape Reference gratefully acknowledge the contributions of previous author Tracy A Glauser, MD to the development and writing of this article.

  1. Flanagan N, O''Connor WJ, McCartan B, et al. Developmental enamel defects in tuberous sclerosis: a clinical genetic marker?. J Med Genet. 1997 Aug. 34(8):637-9. [Medline].

  2. Goodman M, Lamm SH, Engel A, et al. Cortical tuber count: a biomarker indicating neurologic severity of tuberous sclerosis complex. J Child Neurol. 1997 Feb. 12(2):85-90. [Medline].

  3. Everolimus Reduces Kidney Tumors in Tuberous Sclerosis Complex. Medscape Medical News. Jan 11, 2013. [Full Text].

  4. Bissler JJ, Kingswood JC, Radzikowska E, Zonnenberg BA, 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 Jan 10. [Medline].

  5. Van Slegtenhorst M, Nellist M, Nagelkerken B. Interaction between hamartin and tuberin, the TSC1 and TSC2 gene products. Hum Mol Genet. 7(6):1053-7. [Medline].

  6. Nobukini T, Thomas G. The mTOR/S6K signalling pathway: the role of the TSC1/2 tumour suppressor complex and the proto-oncogene Rheb. Novartis Found Symp. 2004. 262:148-54; discussion 154-9, 265-8. [Medline].

  7. 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 Jan. 68(1):64-80. [Medline].

  8. Gates J, Jordan JE. Tuberous sclerosis in old age. South Med J. 1978 Aug. 71(8):974-6. [Medline].

  9. Northrup H, Krueger DA. Tuberous sclerosis complex diagnostic criteria update: recommendations of the 2012 Iinternational Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013 Oct. 49(4):243-54. [Medline]. [Full Text].

  10. Sampson JR, Attwood D, al Mughery AS, Reid JS. Pitted enamel hypoplasia in tuberous sclerosis. Clin Genet. 1992 Jul. 42(1):50-2. [Medline].

  11. Boehler A, Speich R, Russi EW, Weder W. Lung transplantation for lymphangioleiomyomatosis. N Engl J Med. 1996 Oct 24. 335(17):1275-80. [Medline].

  12. Beltramello A, Puppini G, Bricolo A, et al. Does the tuberous sclerosis complex include intracranial aneurysms? A case report with a review of the literature. Pediatr Radiol. 1999 Mar. 29(3):206-11. [Medline].

  13. Takanashi J, Sugita K, Fujii K, Niimi H. MR evaluation of tuberous sclerosis: increased sensitivity with fluid- attenuated inversion recovery and relation to severity of seizures and mental retardation. AJNR Am J Neuroradiol. 1995 Oct. 16(9):1923-8. [Medline].

  14. Bissler JJ, McCormack FX, Young LR, Elwing JM, Chuck G, Leonard JM. Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med. 2008 Jan 10. 358(2):140-51. [Medline].

  15. Dabora SL, Franz DN, Ashwal S, 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(9):e23379. [Medline].

  16. Franz, DN, Leonard, J, Tudor, C. Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Annals of Neurology. 2006 March. 59(3):490-498. [Medline].

  17. Krueger DA, Care MM, Holland K, et al. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. N Engl J Med. 2010 Nov 4. 363(19):1801-11. [Medline].

  18. DeKlotz CM, Ogram AE, Singh S, Dronavalli S, MacGregor JL. Dramatic improvement of facial angiofibromas in tuberous sclerosis with topical rapamycin: optimizing a treatment protocol. Arch Dermatol. 2011 Sep. 147(9):1116-7. [Medline].

  19. Hancock E, Osborne JP. Vigabatrin in the treatment of infantile spasms in tuberous sclerosis: literature review. J Child Neurol. 1999 Feb. 14(2):71-4. [Medline].

  20. Camposano SE, Major P, Halpern E, Thiele EA. Vigabatrin in the treatment of childhood epilepsy: a retrospective chart review of efficacy and safety profile. Epilepsia. 2008 Jul. 49(7):1186-91. [Medline].

  21. Curatolo P, Verdecchia M, Bombardieri R. Vigabatrin for tuberous sclerosis complex. Brain Dev. 2001 Nov. 23(7):649-53. [Medline].

  22. Parisi P, Bombardieri R, Curatolo P. Current role of vigabatrin in infantile spasms. Eur J Paediatr Neurol. 2007 Nov. 11(6):331-6. [Medline].

  23. Willmore LJ, Abelson MB, Ben-Menachem E, Pellock JM, Shields WD. Vigabatrin: 2008 update. Epilepsia. 2009 Feb. 50(2):163-73. [Medline].

  24. Glauser TA. Topiramate. Epilepsia. 1999. 40 Suppl 5:S71-80. [Medline].

  25. Franz DN, Tudor C, Leonard J, et al. Lamotrigine therapy of epilepsy in tuberous sclerosis. Epilepsia. 2001 Jul. 42(7):935-40. [Medline].

  26. Avellino AM, Berger MS, Rostomily RC, et al. Surgical management and seizure outcome in patients with tuberous sclerosis. J Neurosurg. 1997 Sep. 87(3):391-6. [Medline].

  27. Levine NB, Collins J, Franz DN, Crone KR. Gradual formation of an operative corridor by balloon dilation for resection of subependymal giant cell astrocytomas in children with tuberous sclerosis: specialized minimal access technique of balloon dilation. Minim Invasive Neurosurg. 2006 Oct. 49(5):317-20. [Medline].

  28. Asano E, Chugani DC, Muzik O, et al. Autism in tuberous sclerosis complex is related to both cortical and subcortical dysfunction. Neurology. 2001 Oct 9. 57(7):1269-77. [Medline].

  29. Asano E, Chugani DC, Muzik O, et al. Multimodality imaging for improved detection of epileptogenic foci in tuberous sclerosis complex. Neurology. 2000 May 23. 54(10):1976-84. [Medline].

  30. Bolton PF, Griffiths PD. Association of tuberous sclerosis of temporal lobes with autism and atypical autism. Lancet. 1997 Feb 8. 349(9049):392-5. [Medline].

  31. Bowen J, Beasley SW. Rare pulmonary manifestations of tuberous sclerosis in children. Pediatr Pulmonol. 1997 Feb. 23(2):114-6. [Medline].

  32. Bruni O, Cortesi F, Giannotti F, Curatolo P. Sleep disorders in tuberous sclerosis: a polysomnographic study. Brain Dev. 1995 Jan-Feb. 17(1):52-6. [Medline].

  33. Christophe C, Sekhara T, Rypens F, et al. MRI spectrum of cortical malformations in tuberous sclerosis complex. Brain Dev. 2000 Dec. 22(8):487-93. [Medline].

  34. Chugani DC, Chugani HT, Muzik O, et al. Imaging epileptogenic tubers in children with tuberous sclerosis complex using alpha-[11C]methyl-L-tryptophan positron emission tomography. Ann Neurol. 1998 Dec. 44(6):858-66. [Medline].

  35. Crino, PB, Nathanson, KL, Henske, EP. The tuberous sclerosis complex. New England Journal of Medicine. 2006 Sep 28. 355(13):1345-56. [Medline].

  36. El-Hashemite N, Zhang H, Walker V, et al. Perturbed IFN-gamma-Jak-signal transducers and activators of transcription signaling in tuberous sclerosis mouse models: synergistic effects of rapamycin-IFN-gamma treatment. Cancer Res. 2004 May 15. 64(10):3436-43. [Medline].

  37. Enbergs A, Borggrefe M, Kurlemann G, et al. Ventricular tachycardia caused by cardiac rhabdomyoma in a young adult with tuberous sclerosis. Am Heart J. 1996 Dec. 132(6):1263-5. [Medline].

  38. Franz DN. Diagnosis and management of tuberous sclerosis complex. Semin Pediatr Neurol. 1998 Dec. 5(4):253-68. [Medline].

  39. Franz DN, Brody A, Meyer C, et al. Mutational and radiographic analysis of pulmonary disease consistent with lymphangioleiomyomatosis and micronodular pneumocyte hyperplasia in women with tuberous sclerosis. Am J Respir Crit Care Med. 2001 Aug 15. 164(4):661-8. [Medline].

  40. Harding B, Copp AJ. Malformations: tuberous sclerosis. In: Greenfield's Neuropathology. 6th ed. Arnold Edward. 1997:497-502.

  41. Harrison JE, Bolton PF. Annotation: tuberous sclerosis. J Child Psychol Psychiatry. 1997 Sep. 38(6):603-14. [Medline].

  42. Henske EP, Wessner LL, Golden J, et al. Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two-hit model for the pathogenesis of tuberous sclerosis tumors. Am J Pathol. 1997 Dec. 151(6):1639-47. [Medline].

  43. Holley DG, Martin GR, Brenner JI, et al. Diagnosis and management of fetal cardiac tumors: a multicenter experience and review of published reports. J Am Coll Cardiol. 1995 Aug. 26(2):516-20. [Medline].

  44. Hyman MH, Whittemore VH. National Institutes of Health consensus conference: tuberous sclerosis complex. Arch Neurol. 2000 May. 57(5):662-5. [Medline].

  45. Inoki K, Ouyang H, Li Y, Guan KL. Signaling by target of rapamycin proteins in cell growth control. Microbiol Mol Biol Rev. 2005 Mar. 69(1):79-100. [Medline].

  46. Jost CJ, Gloviczki P, Edwards WD, et al. Aortic aneurysms in children and young adults with tuberous sclerosis: report of two cases and review of the literature. J Vasc Surg. 2001 Mar. 33(3):639-42. [Medline].

  47. Jozwiak S, Pedich M, Rajszys P, Michalowicz R. Incidence of hepatic hamartomas in tuberous sclerosis. Arch Dis Child. 1992 Nov. 67(11):1363-5. [Medline].

  48. Kandt RS, Haines JL, Smith M, et al. Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease. Nat Genet. 1992 Sep. 2(1):37-41. [Medline].

  49. Kenerson H, Dundon TA, Yeung RS. Effects of rapamycin in the Eker rat model of tuberous sclerosis complex. Pediatr Res. 2005 Jan. 57(1):67-75. [Medline].

  50. Koprowski C, Rorke LB. Spinal cord lesions in tuberous sclerosis. Pediatr Pathol. 1983 Oct-Dec. 1(4):474-80. [Medline].

  51. Langkau N, Martin N, Brandt R. TSC1 and TSC2 mutations in tuberous sclerosis, the associated phenotypes and a model to explain observed TSC1/ TSC2 frequency ratios. Eur J Pediatr. 2002 Jul. 161(7):393-402. [Medline].

  52. Louis DN, Scheithauer BW, Budka H. Meningiomas. In: Pathology and Genetics of Tumours of the Nervous System. London: Oxford University Press. 2000:176-84.

  53. Maeda M, Tartaro A, Matsuda T, Ishii Y. Cortical and subcortical tubers in tuberous sclerosis and FLAIR sequence. J Comput Assist Tomogr. 1995 Jul-Aug. 19(4):660-1. [Medline].

  54. Mak BC, Yeung RS. The tuberous sclerosis complex genes in tumor development. Cancer Invest. 2004. 22(4):588-603. [Medline].

  55. Miller SP, Tasch T, Sylvain M, et al. Tuberous sclerosis complex and neonatal seizures. J Child Neurol. 1998 Dec. 13(12):619-23. [Medline].

  56. Pui MH, Kong HL, Choo HF. Bone changes in tuberous sclerosis mimicking metastases. Australas Radiol. 1996 Feb. 40(1):77-9. [Medline].

  57. Roach ES, DiMario FJ, Kandt RS, Northrup H. Tuberous Sclerosis Consensus Conference: recommendations for diagnostic evaluation. National Tuberous Sclerosis Association. J Child Neurol. 1999 Jun. 14(6):401-7. [Medline].

  58. Roach ES, Gomez MR, Northrup H. Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. J Child Neurol. 1998 Dec. 13(12):624-8. [Medline].

  59. Sener N. Tuberous sclerosis: diffusion MRI findings in the brain. Eur Radiol. 2002 Jan. 12(1):138-43. [Medline].

  60. Seri S, Cerquiglini A, Pisani F, et al. Frontal lobe epilepsy associated with tuberous sclerosis: electroencephalographic-magnetic resonance image fusioning. J Child Neurol. 1998 Jan. 13(1):33-8. [Medline].

  61. Shepherd CW, Houser OW, Gomez MR. MR findings in tuberous sclerosis complex and correlation with seizure development and mental impairment. AJNR Am J Neuroradiol. 1995 Jan. 16(1):149-55. [Medline].

  62. Webb DW, Fryer AE, Osborne JP. Morbidity associated with tuberous sclerosis: a population study. Dev Med Child Neurol. 1996 Feb. 38(2):146-55. [Medline].

  63. Webb DW, Thomas RD, Osborne JP. Cardiac rhabdomyomas and their association with tuberous sclerosis. Arch Dis Child. 1993 Mar. 68(3):367-70. [Medline].

  64. Weber AM, Egelhoff JC, McKellop JM, Franz DN. Autism and the cerebellum: evidence from tuberous sclerosis. J Autism Dev Disord. 2000 Dec. 30(6):511-7. [Medline].

Enhancing subependymal nodules, including a probable giant cell astrocytoma in the region of the foramen of Monro. Subependymal nodules may increase in size over time from one scan to the next, and then stabilize. This lesion had not changed with serial imaging over 2 years. The patient remains asymptomatic and is monitored closely for any deterioration.
Hydrocephalus from a subependymal giant cell astrocytoma in a patient with tuberous sclerosis. The patient presented with acute blindness and ataxia.
Facial angiofibromas in a young man with tuberous sclerosis complex.
Dysplastic periungual fibroma involving the great toe in a patient with tuberous sclerosis.
Gingival fibromas (see arrows) in a patient with tuberous sclerosis. A stain outlines dental pits and craters. Gingival hyperplasia from other causes (eg, phenytoin use) is more diffuse and usually not nodular/focal in nature.
Typical ash leaf macules; the reddish, nodular area at the upper lumbar area is a shagreen patch.
Atrial rhabdomyoma as seen on cardiac CT scan in a patient with tuberous sclerosis.
Nonobstructive ventricular rhabdomyomas in a patient with tuberous sclerosis.
Ventricular rhabdomyomas may diffusely infiltrate the myocardium, as in this patient with tuberous sclerosis. The patient presented with cardiac failure and hydrops at birth. After a period of intensive supportive care and inotropic therapy, she now has essentially normal cardiac function and is on no medications.
Multifocal pulmonary cysts characteristic of lymphangiomyomatosis. As many as 40% of women with tuberous sclerosis have pulmonary cysts on chest CT scan.
Massive bilateral angiomyolipomas in a woman with tuberous sclerosis. She also has lymphangiomyomatosis.
Pre-embolization angiography of the patient with angiomyolipomas shown the previous image. Dysplastic arterial vessels are demonstrated.
Vessels to the angiomyolipoma shown in the previous image have been occluded with coils. This should produce regression of the lesion and prevention of hemorrhage. Functional intervening renal parenchyma is preserved.
Enamel pitting in tuberous sclerosis. Pinpoint size pitting (A) and crater size pitting (B) are visible. Red dye is used to enhance recognition.
Basilar artery aneurysm in a 2-year-old girl with tuberous sclerosis. The arrow shows the anterior aspect of the aneurysm where it abuts the clivus. The lesion was not present on MRI performed 11 months earlier.
This presumed tuber was first noted in the left frontal region. It expanded in size, affecting adjacent structures across the midline and resulting in calcifications still evident in the right frontal region. The tuber then spontaneously involuted. About 20% of tubers may show changes in imaging characteristics over time, requiring close imaging follow-up. This patient remained asymptomatic from the mass effect, and his seizures resolved as the lesion involuted.
This father and all 3 children have tuberous sclerosis complex. The children are now grown up and of normal intelligence, including the young lady at left who is cushingoid from therapy with adrenocorticotropic hormone for infantile spasms.
The child whose CT scan is shown presented with medically intractable epilepsy thought to be due to partial hemimegalencephaly. She became seizure free after partial hemispherectomy. Pathology was consistent with a cortical tuber. She was subsequently found to have multiple ash leaf macules and diagnosed with tuberous sclerosis.
Multiple tubers in a child with tuberous sclerosis, normal intelligence, and well-controlled seizures. High tuber count does not invariably mean poor neurological outcome.
All tubers are not equal. This child has a smaller number of tubers than the patient shown in the previous image, but the tubers are larger in size. She too has normal intelligence and is seizure free on medication.
Mammalian target of rapamycin (mTOR) activates the protein S6 kinase, which enhances cell growth and protein synthesis. It, in turn, is regulated by multiple factors, including insulin, amino acids, the drugs rapamycin and its congeners (eg, RAD001), and the TSC gene products via the GTPase-activating protein Rheb.
Subependymal giant cell astrocytoma prior to stereotactic insertion of balloon catheter as seen on T2-weighted MRI.
Modified angioplasty catheter used in creation of surgical tract for astrocytoma resection.
Catheter placed in proximity to lesion, balloon inflated.
Postoperative T2-weighted MRI in a patient with subependymal giant cell astrocytoma showing gross total resection of giant cell astrocytoma with minimal disruption of overlying cortex.
Mean reduction in simple and complex partial seizures in patients with tuberous sclerosis complex (TSC) who were treated with vagus nerve stimulator at the author's institution at 6 and 12 months. Overall reduction in secondarily generalized seizures was 22% at 12 months (N = 17; 10 boys, 7 girls, aged 3-12 y).
Regression of a giant cell astrocytoma after approximately 15 months oral rapamycin therapy in a 4-year-old patient with tuberous sclerosis.
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.