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


Genetics of Tuberous Sclerosis Workup

  • Author: Robert A Schwartz, MD, MPH; Chief Editor: Luis O Rohena, MD  more...
Updated: Mar 27, 2015

Laboratory Studies

Some recommend annual urinalysis and electrolyte testing to detect progression of renal lesions in patients with tuberous sclerosis complex (TSC), although this testing is controversial.

Testing to determine genetic mutations is now available only on a clinical basis. Once a person affected with tuberous sclerosis complex is found to have a mutation in either of the 2 genes, at risk family members may be tested. Current information is available online from GeneTests.

MRI with the fluid-attenuated inversion recovery (FLAIR) sequence of cystlike cortical tubers was performed in patients with tuberous sclerosis complex.[36] FLAIR images confirmed the cystic character of some of these cortical tubers.

Renal cell carcinomas were divided in TSC into three different morphologic groups (Yang et al, 2014). The largest group were classified as "TSC-associated papillary renal cell carcinomas."


Imaging Studies

Brain MRI or CT scanning

Brain MRI is recommended for the detection and follow-up imaging of cortical tubers, subependymal nodules (SENs), and subependymal giant cell astrocytomas (SEGAs). Perform MRI during the initial diagnostic workup and then every 1-3 years in children with tuberous sclerosis complex. MRI may be performed less frequently in adults without lesions and as clinically indicated in adults with lesions. In addition, perform MRI in family members if results of physical examinations are negative or are not definitive for a diagnosis. MRI is preferred over CT scanning because of improved depiction of lesions and the lack of radiation exposure on repeat examinations.

Cortical tubers, best detected using T2-weighted MRI sequences, often develop in the gray-white junction. On T2-weighted images, cortical tubers demonstrate increased signal intensity and are often wedge shaped (tuber) or linear shaped (radial migration lines). Conversely, cortical tubers demonstrate decreased signal intensity on T1-weighted images. Previously believed to be pathognomonic, cortical tubers are no longer considered specific for tuberous sclerosis complex because isolated cortical dysplasia may demonstrate similar radiologic features. The number of tubers detected using MRI appears to be correlated with the severity of mental retardation or seizures.

SENs are located in the ventricles and often become calcified. The lesions are best detected using CT, although they are sometimes found using MRI or plain radiography if they are calcified. SENs demonstrate a candle-dripping appearance.

SENs may grow and give rise to SEGAs. A SEGA may cause obstruction, with evidence of hydrocephalus or mass effect in some patients. The lesions usually appear in the region of the Monro foramen, are partially calcified, and are often larger than 2 cm. Detection of SEGAs is slightly more sensitive using MRI than using CT scanning. The clinical presentation of TSC is highly variable and not well understood. SEGAs are found to be linked with autistic spectrum disorders in patients with TSC, suggesting that SEGA formation may also predispose (Kothare et al, 2014).

Renal ultrasonography, CT scanning, or MRI

Ultrasonography is usually preferred over CT scanning and MRI because of availability and cost. Ultrasonography is more sensitive in detecting renal lesions than CT scanning. Perform a study at initial diagnosis or evaluation and also in family members of patients with tuberous sclerosis complex. Perform subsequent surveillance studies in children or adults with tuberous sclerosis complex every 1-3 years. In those with renal lesions, perform studies every 6-12 months until no further growth occurs or lesions begin to regress.

Ultrasonography, CT scanning, or MRI may reveal evidence of benign or malignant angiomyolipomas, renal cysts, or, rarely, renal cell carcinoma. Avoid CT as much as possible to minimize radiation. Benign angiomyolipomas are found in 50-80% of patients with tuberous sclerosis complex. The lesions are usually bilateral, and the average size is 9 cm. Angiomyolipomas are more common in adults with tuberous sclerosis complex, whereas renal cysts are more common in children.


Obtain an echocardiogram at initial evaluation and in adults with tuberous sclerosis complex as clinically indicated. In children with previously detected lesions, obtain an echocardiogram every 6-12 months until lesions cease growing or begin to regress.

Cardiac rhabdomyomas occur in 50-70% of patients with tuberous sclerosis complex. Tumors almost always regress as the child ages. Occasionally, lesions are not detected using echocardiography, although they may still cause arrhythmia.

Pulmonary CT scanning or plain radiography

Obtain a CT scan of the lung in adult females with tuberous sclerosis complex beginning at age 18 years, even in the absence of symptoms. Pulmonary pathology is almost nonexistent in males. The average age of onset of pulmonary symptoms is in the early fourth decade of life.

Pulmonary lesions that may be detected on CT scans include lymphangioleiomyomatosis (LAM), clear cell tumors, and multifocal multinodular pneumocyte hyperplasia.

Plain radiography of the chest may reveal a honeycomb appearance due to the presence of multiple subpleural cysts.


Other Tests


EEG is not diagnostically helpful; obtain EEGs only in patients with a history of doubtful seizures.

EEG may reveal a hypsarrhythmia pattern in an infant with infantile spasms.

Onset of partial seizures is often localized to the frontal and temporal regions.

The interictal sleep EEG was recently recognized to have high sensitivity and positive predictive value in the neurologic outcome and seizure control of patients with tuberous sclerosis complex, with abnormal EEG results correlating with a worse outcome.

Neurodevelopmental testing

Perform neurodevelopmental testing in children at the time of diagnosis and in children with tuberous sclerosis complex entering the first grade. In children and adults with a history of developmental delay, perform repeated evaluations as clinically indicated.


Obtain ECGs with the same frequency as echocardiograms (ie, initial evaluation, as indicated in adults with tuberous sclerosis complex and cardiac lesions, and every 6-12 mo in children with known cardiac lesions).

Various arrhythmias or conduction defects may be noted on ECGs.

Funduscopic examination

Perform a funduscopic examination during the initial workup, when evaluating family members, and as clinically indicated in patients with tuberous sclerosis complex and known ophthalmologic lesions.

Funduscopic examination may reveal retinal hamartomas or astrocytomas in 50-80% of individuals with tuberous sclerosis complex. The lesions may have a rounded or multinodular appearance. Initially, lesions are semitranslucent or translucent but often calcify and become whitish with time.

An abnormal red reflex may also be present and may be confused with retinoblastoma.

Papilledema may be detected in the presence of increased intracranial pressure.

Pulmonary function testing

Some recommend performing pulmonary function tests (PFTs) in postpubertal females with tuberous sclerosis complex. PFT results in individuals with tuberous sclerosis complex usually demonstrate an obstructive pattern.


Histologic Findings

Tubers are dysplastic disorganized regions within the cortex, with a loss of structured pattern. The gray-white border is usually blurred. Astrocytes, neurons, and giant cells appear abnormal. The surrounding unaffected areas appear completely normal.

SENs and SEGAs are also composed of neurons, giant cells, and astrocytes. SENs and SEGAs are denser than tubers; therefore, they are sometimes confused with malignant tumors.

Periungual fibromas are nonencapsulated neoplasms composed of stellate fibroblasts admixed with vertically oriented dense collagen and blood vessels. Histologic variants of periungual fibromas in tuberous sclerosis complex have been classified as angiomatous, fibrotic, and intermediate mixed subtypes, depending on the relative proportion of vascular and stromal components.[22]

Contributor Information and Disclosures

Robert A Schwartz, MD, MPH Professor and Head of Dermatology, Professor of Pathology, Pediatrics, Medicine, and Preventive Medicine and Community Health, Rutgers New Jersey Medical School; Visiting Professor, Rutgers University School of Public Affairs and Administration

Robert A Schwartz, MD, MPH is a member of the following medical societies: Alpha Omega Alpha, New York Academy of Medicine, American Academy of Dermatology, American College of Physicians, Sigma Xi

Disclosure: Nothing to disclose.


Robert Pedersen, MD Chief, Child Neurology, Tripler Army Medical Center; Clinical Professor, Pediatrics and Psychiatry, University of Hawaii, John A Burns School of Medicine

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

Disclosure: Nothing to disclose.

Sergiusz Jozwiak, MD, PhD Professor and Head of Pediatric Neurology, Warsaw Medical University, Poland

Sergiusz Jozwiak, MD, PhD is a member of the following medical societies: Sigma Xi

Disclosure: Received honoraria from Novartis for speaking and teaching.

Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Nothing to disclose.

Chief Editor

Luis O Rohena, MD Chief, Medical Genetics, San Antonio Military Medical Center; Assistant Professor of Pediatrics, Uniformed Services University of the Health Sciences, F Edward Hebert School of Medicine; Assistant Professor of Pediatrics, University of Texas Health Science Center at San Antonio

Luis O Rohena, MD is a member of the following medical societies: American Academy of Pediatrics, American Chemical Society, American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.

Additional Contributors

Erawati V Bawle, MD, FAAP, FACMG Retired Professor, Department of Pediatrics, Wayne State University School of Medicine

Erawati V Bawle, MD, FAAP, FACMG is a member of the following medical societies: American College of Medical Genetics and Genomics, American Society of Human Genetics

Disclosure: Nothing to disclose.


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

  1. Borkowska J, Schwartz RA, Jozwiak S. Recent perspectives on diagnosis and treatment of tuberous sclerosis complex in children. Int J Disability Human Development. 2009. 8:369-375.

  2. Crino PB, Henske EP. New developments in the neurobiology of the tuberous sclerosis complex. Neurology. 1999 Oct 22. 53(7):1384-90. [Medline].

  3. Borkowska J, Schwartz RA, Kotulska K, Jozwiak S. Tuberous sclerosis complex: tumors and tumorigenesis. Int J Dermatol. 2011 Jan. 50(1):13-20. [Medline].

  4. Krishnan ML, Commowick O, Jeste SS, et al. Diffusion features of white matter in tuberous sclerosis with tractography. Pediatr Neurol. 2010 Feb. 42(2):101-6. [Medline]. [Full Text].

  5. Jozwiak J. Hamartin and tuberin: working together for tumour suppression. Int J Cancer. 2006 Jan 1. 118(1):1-5. [Medline].

  6. Jozwiak J, Jozwiak S. Giant cells: contradiction to two-hit model of tuber formation?. Cell Mol Neurobiol. 2005 Aug. 25(5):795-805. [Medline].

  7. Jozwiak J, Wlodarski P. Hamartin and tuberin modulate gene transcription via beta-catenin. J Neurooncol. 2006 Sep. 79(3):229-34. [Medline].

  8. Jozwiak J, Grajkowska W, Kotulska K, Jozwiak S, Zalewski W, Zajaczkowska A. Brain tumor formation in tuberous sclerosis depends on Erk activation. Neuromolecular Med. 2007. 9(2):117-27. [Medline].

  9. Jozwiak J, Jozwiak S, Wlodarski P. Possible mechanisms of disease development in tuberous sclerosis. Lancet Oncol. 2008 Jan. 9(1):73-9. [Medline].

  10. Jozwiak J, Sahin M, Jozwiak S, et al. Cardiac rhabdomyoma in tuberous sclerosis: hyperactive Erk signaling. Int J Cardiol. 2009 Feb 6. 132(1):145-7. [Medline].

  11. Mayer K, Fonatsch C, Wimmer K, van den Ouweland AM, Maat-Kievit AJ. Clinical utility gene card for: Tuberous sclerosis complex (TSC1, TSC2). Eur J Hum Genet. 2013 Jun 12. [Medline].

  12. Yu Z, Zhang X, Guo H, et al. A novel TSC2 mutation in a Chinese family with tuberous sclerosis complex. J Genet. 2014 Apr. 93(1):169-72. [Medline].

  13. Priolo C, Ricoult SJ, Khabibullin D, et al. TSC2 Loss Increases Lysophosphatidylcholine Synthesis in Lymphangioleiomyomatosis. Am J Respir Cell Mol Biol. 2015 Mar 17. [Medline].

  14. Tyburczy ME, Jozwiak S, Malinowska IA, et al. A shower of second hit events as the cause of multifocal renal cell carcinoma in tuberous sclerosis complex. Hum Mol Genet. 2015 Apr 1. 24(7):1836-42. [Medline].

  15. Jang MA, Hong SB, Lee JH, Lee MH, Chung MP, Shin HJ, et al. Identification of TSC1 and TSC2 Mutations in Korean Patients With Tuberous Sclerosis Complex. Pediatr Neurol. 2012 Apr. 46(4):222-4. [Medline].

  16. Józwiak J, Sontowska I, Ploski R. Frequency of TSC1 and TSC2 mutations in American, British, Polish and Taiwanese populations. Mol Med Rep. 2013 Sep. 8(3):909-13. [Medline].

  17. Grajkowska W, Kotulska K, Jurkiewicz E, Matyja E. Brain lesions in tuberous sclerosis complex. Review. Folia Neuropathol. 2010. 48(3):139-49. [Medline].

  18. Jozwiak S, Schwartz RA, Janniger CK, Michalowicz R, Chmielik J. Skin lesions in children with tuberous sclerosis complex: their prevalence, natural course, and diagnostic significance. Int J Dermatol. 1998 Dec. 37(12):911-7. [Medline].

  19. Schwartz RA, Fernandez G, Kotulska K, Jozwiak S. Tuberous sclerosis complex: advances in diagnosis, genetics, and management. J Am Acad Dermatol. 2007 Aug. 57(2):189-202. [Medline].

  20. Rama Rao GR, Krishna Rao PV, Gopal KV, Kumar YH, Ramachandra BV. Forehead plaque: a cutaneous marker of CNS involvement in tuberous sclerosis. Indian J Dermatol Venereol Leprol. 2008 Jan-Feb. 74(1):28-31. [Medline].

  21. Quist SR, Franke I, Sutter C, Bartram CR, Gollnick HP, Leverkus M. Periungual fibroma (Koenen tumors) as isolated sign of tuberous sclerosis complex with tuberous sclerosis complex 1 germline mutation. J Am Acad Dermatol. 2010 Jan. 62(1):159-61. [Medline].

  22. Ma D, Darling T, Moss J, Lee CC. Histologic variants of periungual fibromas in tuberous sclerosis complex. J Am Acad Dermatol. 2011 Feb. 64(2):442-4. [Medline]. [Full Text].

  23. Moudouni SM, Tligui M, Sibony M, Doublet JD, Haab F, Gattegno B. Malignant epithelioid renal angiomyolipoma involving the inferior vena cava in a patient with tuberous sclerosis. Urol Int. 2008. 80(1):102-4; discussion 104. [Medline].

  24. Jozwiak S, Domanska-Pakiela D, Kwiatkowski DJ, Kotulska K. Multiple cardiac rhabdomyomas as a sole symptom of tuberous sclerosis complex: case report with molecular confirmation. J Child Neurol. 2005 Dec. 20(12):988-9. [Medline].

  25. Martignoni G, Pea M, Reghellin D, et al. Molecular pathology of lymphangioleiomyomatosis and other perivascular epithelioid cell tumors. Arch Pathol Lab Med. 2010 Jan. 134(1):33-40. [Medline].

  26. Sparling JD, Hong CH, Brahim JS, Moss J, Darling TN. Oral findings in 58 adults with tuberous sclerosis complex. J Am Acad Dermatol. 2007 May. 56(5):786-90. [Medline].

  27. Hasselblatt M, Jozwiak J, Mayer K, et al. Hypothalamic papillary tumor in a patient with tuberous sclerosis. Am J Surg Pathol. 2008 Oct. 32(10):1578-80. [Medline].

  28. McMaster ML, Goldstein AM, Parry DM. Clinical features distinguish childhood chordoma associated with tuberous sclerosis complex (TSC) from chordoma in the general paediatric population. J Med Genet. 2011 Jan 25. [Medline].

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

  30. [Guideline] Roach ES, Sparagana SP. Diagnosis of tuberous sclerosis complex. J Child Neurol. 2004 Sep. 19(9):643-9. [Medline].

  31. Jozwiak S, Schwartz RA, Janniger CK, Bielicka-Cymerman J. Usefulness of diagnostic criteria of tuberous sclerosis complex in pediatric patients. J Child Neurol. 2000 Oct. 15(10):652-9. [Medline].

  32. Rok P, Kasprzyk-Obara J, Domanska-Pakiela D, Jozwiak S. Clinical symptoms of tuberous sclerosis complex in patients with an identical TSC2 mutation. Med Sci Monit. 2005 May. 11(5):CR230-234. [Medline].

  33. Staley BA, Vail EA, Thiele EA. Tuberous sclerosis complex: diagnostic challenges, presenting symptoms, and commonly missed signs. Pediatrics. 2011 Jan. 127(1):e117-25. [Medline]. [Full Text].

  34. Huggins RH, Janusz CA, Schwartz RA. Vitiligo: a sign of systemic disease. Indian J Dermatol Venereol Leprol. 2006 Jan-Feb. 72(1):68-71. [Medline].

  35. Arva NC, Pappas JG, Bhatla T, Raetz EA, Macari M, Ginsburg HB, et al. Well-differentiated pancreatic neuroendocrine carcinoma in tuberous sclerosis--case report and review of the literature. Am J Surg Pathol. 2012 Jan. 36(1):149-53. [Medline].

  36. Jurkiewicz E, Jozwiak S, Bekiesinska-Figatowska M, Pakula-Kosciesza I, Walecki J. Cyst-like cortical tubers in patients with tuberous sclerosis complex: MR imaging with the FLAIR sequence. Pediatr Radiol. 2006 Jun. 36(6):498-501. [Medline].

  37. Jozwiak J, Jozwiak S, Oldak M. Molecular activity of sirolimus and its possible application in tuberous sclerosis treatment. Med Res Rev. 2006 Mar. 26(2):160-80. [Medline].

  38. Paghdal KV, Schwartz RA. Sirolimus (rapamycin): from the soil of Easter Island to a bright future. J Am Acad Dermatol. 2007 Dec. 57(6):1046-50. [Medline].

  39. Davies DM, Johnson SR, Tattersfield AE, Kingswood JC, Cox JA, McCartney DL. Sirolimus therapy in tuberous sclerosis or sporadic lymphangioleiomyomatosis. N Engl J Med. 2008 Jan 10. 358(2):200-3. [Medline].

  40. 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].

  41. Hauptman JS. From the bench to the bedside: Everolimus for subependymal giant cell astrocytomas in Tuberous sclerosis complex, optic nerve regeneration, targeted cytotoxins for gliomas. Surg Neurol Int. 2011 Jan 14. 2:2. [Medline]. [Full Text].

  42. Nawashiro H, Shinomiya N. Everolimus and giant-cell astrocytomas in tuberous sclerosis. N Engl J Med. 2011 Feb 10. 364(6):576-7. [Medline].

  43. Perek-Polnik M, Józwiak 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 Jan. 16(1):83-5. [Medline].

  44. Józwiak S, Kotulska K, Domanska-Pakiela 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 Sep. 15(5):424-31. [Medline].

  45. Wu JY, Salamon N, Kirsch HE, et al. Noninvasive testing, early surgery, and seizure freedom in tuberous sclerosis complex. Neurology. 2010 Feb 2. 74(5):392-8. [Medline]. [Full Text].

  46. Matsuyama K, Ohsawa I, Ogawa T. Do children with tuberous sclerosis complex have superior musical skill? - A unique tendency of musical responsiveness in children with TSC. Med Sci Monit. 2007 Mar 27. 13(4):CR156-164. [Medline].

  47. Kingswood JC, Jozwiak S, Belousova ED, Frost MD, Kuperman RA, Bebin EM, et al. The effect of everolimus on renal angiomyolipoma in patients with tuberous sclerosis complex being treated for subependymal giant cell astrocytoma: subgroup results from the randomized, placebo-controlled, Phase 3 trial EXIST-1. Nephrol Dial Transplant. 2014 Jun. 29(6):1203-10. [Medline].

  48. Roth J, Roach ES, Bartels U, Józwiak S, Koenig MK, Weiner HL, et al. Subependymal giant cell astrocytoma: diagnosis, screening, and treatment. Recommendations from the International Tuberous Sclerosis Complex Consensus Conference 2012. Pediatr Neurol. 2013 Dec. 49(6):439-44. [Medline].

  49. Trelinska J, Dachowska I, Kotulska K, et al. Complications of mammalian target of rapamycin inhibitor anticancer treatment among patients with tuberous sclerosis complex are common and occasionally life-threatening. Anticancer Drugs. 2015 Apr. 26(4):437-42. [Medline].

  50. Brodie MJ. Lamotrigine--an update. Can J Neurol Sci. 1996 Nov. 23(4):S6-9. [Medline].

  51. Brodie MJ, Dichter MA. Antiepileptic drugs. N Engl J Med. 1996 Jan 18. 334(3):168-75. [Medline].

  52. Kaczorowska M, Jurkiewicz E, Domanska-Pakiela D, et al. Cerebral tuber count and its impact on mental outcome of patients with tuberous sclerosis complex. Epilepsia. 2011 Jan. 52(1):22-7. [Medline].

  53. Pressey JG, Wright JM, Geller JI, Joseph DB, Pressey CS, Kelly DR. Sirolimus therapy for fibromatosis and multifocal renal cell carcinoma in a child with tuberous sclerosis complex. Pediatr Blood Cancer. 2010 Jan 27. [Medline].

  54. Curatolo P, Bombardieri R, Jozwiak S. Tuberous sclerosis. Lancet. 2008 Aug 23. 372(9639):657-68. [Medline].

  55. 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].

  56. de Vries PJ, Watson P. Attention deficits in tuberous sclerosis complex (TSC): rethinking the pathways to the endstate. J Intellect Disabil Res. 2007 Dec 19. [Medline].

  57. Dichter MA, Brodie MJ. New antiepileptic drugs. N Engl J Med. 1996 Jun 13. 334(24):1583-90. [Medline].

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

  59. Haslam RH. Nonfebrile seizures. Pediatr Rev. 1997 Feb. 18(2):39-49. [Medline].

  60. Hoogeveen-Westerveld M, Wentink M, van den Heuvel D, et al. Functional assessment of variants in the TSC1 and TSC2 genes identified in individuals with Tuberous Sclerosis Complex. Hum Mutat. 2011 Feb 1. [Medline].

  61. Hurst JS, Wilcoski S. Recognizing an index case of tuberous sclerosis. Am Fam Physician. 2000 Feb 1. 61(3):703-8, 710. [Medline].

  62. Husain AM, Foley CM, Legido A, et al. Tuberous sclerosis complex and epilepsy: prognostic significance of electroencephalography and magnetic resonance imaging. J Child Neurol. 2000 Feb. 15(2):81-3. [Medline].

  63. Jozwiak J, Galus R. Molecular implications of skin lesions in tuberous sclerosis. Am J Dermatopathol. 2008 Jun. 30(3):256-61. [Medline].

  64. Jozwiak J, Kotulska K, Lojek M, et al. Fibroblasts from normal skin of a tuberous sclerosis patient show upregulation of mTOR pathway. Am J Dermatopathol. 2009 Feb. 31(1):68-70. [Medline].

  65. Jozwiak J, Sahin M, Jozwiak S, et al. Cardiac rhabdomyoma in tuberous sclerosis: Hyperactive Erk signaling. Int J Cardiol. 2007 Nov 23. [Medline].

  66. Jozwiak S, Domanska-Pakiela D, Kotulska K, Kaczorowska M. Treatment before seizures: new indications for antiepileptic therapy in children with tuberous sclerosis complex. Epilepsia. 2007 Aug. 48(8):1632; author reply 1632-4. [Medline].

  67. Jozwiak S, Kotulska K, Kasprzyk-Obara J, Domanska-Pakiela D, Tomyn-Drabik M, Roberts P. Clinical and genotype studies of cardiac tumors in 154 patients with tuberous sclerosis complex. Pediatrics. 2006 Oct. 118(4):e1146-51. [Medline].

  68. Jurkiewicz E, Jozwiak S. Giant intracranial aneurysm in a 9-year-old boy with tuberous sclerosis. Pediatr Radiol. 2006 May. 36(5):463. [Medline].

  69. Korf BR. Neurocutaneous syndromes: neurofibromatosis 1, neurofibromatosis 2, and tuberous sclerosis. Curr Opin Neurol. 1997 Apr. 10(2):131-6. [Medline].

  70. Kothare SV, Singh K, Chalifoux JR, Staley BA, Weiner HL, Menzer K, et al. Severity of manifestations in tuberous sclerosis complex in relation to genotype. Epilepsia. 2014 Jul. 55(7):1025-9. [Medline].

  71. Kothare SV, Singh K, Hochman T, Chalifoux JR, Staley BA, Weiner HL, et al. Genotype/phenotype in tuberous sclerosis complex: associations with clinical and radiologic manifestations. Epilepsia. 2014 Jul. 55(7):1020-4. [Medline].

  72. Kotulska K, Borkowska J, Mandera M, Roszkowski M, Jurkiewicz E, Grajkowska W, et al. Congenital subependymal giant cell astrocytomas in patients with tuberous sclerosis complex. Childs Nerv Syst. 2014 Sep 17. [Medline].

  73. Krymskaya VP, Goncharova EA. PI3K/mTORC1 activation in hamartoma syndromes: Therapeutic prospects. Cell Cycle. 2009 Feb 6. 8(3):[Medline].

  74. Martin N, Debussche C, De Broucker T, et al. Gadolinium-DTPA enhanced MR imaging in tuberous sclerosis. Neuroradiology. 1990. 31(6):492-7. [Medline].

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

  76. Monaghan HP, Krafchik BR, MacGregor DL, Fitz CR. Tuberous sclerosis complex in children. Am J Dis Child. 1981 Oct. 135(10):912-7. [Medline].

  77. Morse RP. Tuberous sclerosis. Arch Neurol. 1998 Sep. 55(9):1257-8. [Medline].

  78. Nakase Y, Fukuda K, Chikashige Y, et al. A defect in protein farnesylation suppresses a loss of Schizosaccharomyces pombe tsc2+, a homolog of the human gene predisposing to tuberous sclerosis complex. Genetics. 2006 Jun. 173(2):569-78. [Medline]. [Full Text].

  79. O'Hagan AR, Ellsworth R, Secic M, Rothner AD, Brouhard BH. Renal manifestations of tuberous sclerosis complex. Clin Pediatr (Phila). 1996 Oct. 35(10):483-9. [Medline].

  80. 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].

  81. Roach ES, Williams DP, Laster DW. Magnetic resonance imaging in tuberous sclerosis. Arch Neurol. 1987 Mar. 44(3):301-3. [Medline].

  82. Shepherd CW, Gomez MR, Lie JT, Crowson CS. Causes of death in patients with tuberous sclerosis. Mayo Clin Proc. 1991 Aug. 66(8):792-6. [Medline].

  83. Stefansson K. Tuberous sclerosis. Mayo Clin Proc. 1991 Aug. 66(8):868-72. [Medline].

  84. Wlodarski PK, Maksym R, Oldak M, Jozwiak S, Wojcik A, Jozwiak J. Tuberin-heterozygous cell line TSC2ang1 as a model for tuberous sclerosis-associated skin lesions. Int J Mol Med. 2008 Feb. 21(2):245-50. [Medline].

Facial angiofibroma, previously termed adenoma sebaceum, in a patient with tuberous sclerosis complex (TSC).
Forehead plaque in a patient with tuberous sclerosis complex (TSC). The presence of either a forehead plaque or a facial angiofibroma constitutes one of the major diagnostic criteria for TSC.
Ash-leaf spots are hypomelanotic lesions that are observed more easily with the use of a Wood lamp.
A shagreen patch is a connective tissue hamartoma with a leathery texture and is found most commonly in the lower back region.
Confetti skin lesions are hypomelanotic lesions that cluster and appear reticulated.
MRI in a patient with tuberous sclerosis complex (TSC) demonstrates the presence of a tuber and subependymal nodules.
Periungual fibroma on the thumb of a patient with tuberous sclerosis complex (TSC).
All material on this website is protected by copyright, Copyright © 1994-2016 by WebMD LLC. This website also contains material copyrighted by 3rd parties.