Advertisement

Pediatric Radiology

, Volume 38, Issue 9, pp 936–952 | Cite as

The pathogenesis and imaging of the tuberous sclerosis complex

  • Henry J. BaskinJr.
Review

Abstract

Tuberous sclerosis complex (TSC) is an autosomal-dominant disorder characterized by the formation of hamartomatous lesions in multiple organ systems. It is the second most common neurocutaneous syndrome after neurofibromatosis type 1 and has been recognized since the late 1800s. Although the disease has complete penetrance, there is also high phenotypic variability: some patients have obvious signs at birth, while others remain undiagnosed for many years. In addition to skin lesions, TSC patients develop numerous brain lesions, angiomyolipoma (AMLs), lymphangiomyomatosis (LAM) in the lungs, cardiac rhabdomyomas, skeletal lesions, and vascular anomalies, all of which are well seen with medical imaging. Our knowledge of TSC genetics and pathophysiology has expanded dramatically in recent years: two genetic loci were discovered in the 1990s and recent elucidation of TSC’s interaction with the mTOR pathway has changed how we manage the disease. Meanwhile, medical imaging is playing an increasingly important role in the diagnosis, management, and treatment of TSC. We provide an update on the genetics and pathophysiology of TSC, review its clinical manifestations, and explore the breadth of imaging features in each organ system, from prenatal detection of cardiac rhabdomyomas to monitoring rapamycin therapy to treatment of AMLs by interventional radiology.

Keywords

Tuberous sclerosis Angiomyolipoma PEComa SEGA Children 

References

  1. 1.
    Hurst JS, Wilcoski S (2000) Recognizing an index case of tuberous sclerosis. Am Fam Physician 61:703–708, 710PubMedGoogle Scholar
  2. 2.
    Sybert VP, Hall JG (1979) Inheritance of tuberous sclerosis. Lancet 1:783PubMedGoogle Scholar
  3. 3.
    Crino PB, Nathanson KL, Henske EP (2006) The tuberous sclerosis complex. N Engl J Med 355:1345–1356PubMedGoogle Scholar
  4. 4.
    Webb DW, Clarke A, Fryer A et al (1996) The cutaneous features of tuberous sclerosis: a population study. Br J Dermatol 135:1–5PubMedGoogle Scholar
  5. 5.
    Prather P, de Vries PJ (2004) Behavioral and cognitive aspects of tuberous sclerosis complex. J Child Neurol 19:666–674PubMedGoogle Scholar
  6. 6.
    van Baal JG, Fleury P, Brummelkamp WH (1989) Tuberous sclerosis and the relation with renal angiomyolipoma. A genetic study on the clinical aspects. Clin Genet 35:167–173PubMedCrossRefGoogle Scholar
  7. 7.
    Maria BL, Deidrick KM, Roach ES et al (2004) Tuberous sclerosis complex: pathogenesis, diagnosis, strategies, therapies, and future research directions. J Child Neurol 19:632–642PubMedGoogle Scholar
  8. 8.
    Jansen FE, van Nieuwenhuizen O, van Huffelen AC (2004) Tuberous sclerosis complex and its founders. J Neurol Neurosurg Psychiatry 75:770PubMedGoogle Scholar
  9. 9.
    Pringle JJ (1890) A case of congenital adenoma sebaceum. Br J Dermatol 2:1–14Google Scholar
  10. 10.
    National Institute of Neurological Disorders and Stroke (2007) Tuberous sclerosis fact sheet. NIH publication no. 02-1846. National Institutes of Health, Bethesda, MDGoogle Scholar
  11. 11.
    Gomez MR, Sampson JR, Whittemore VH (1999) Tuberous sclerosis complex. Oxford University Press, New YorkGoogle Scholar
  12. 12.
    European Chromosome 16 Tuberous Sclerosis Consortium (1993) Identification and characterization of the tuberous sclerosis gene on chromosome 16. Cell 75:1305–1315Google Scholar
  13. 13.
    van Slegtenhorst M, de Hoogt R, Hermans C et al (1997) Identification of the tuberous sclerosis gene TSC1 on chromosome 9q34. Science 277:805–808PubMedGoogle Scholar
  14. 14.
    Knudson AG Jr (1971) Mutation and cancer: statistical study of retinoblastoma. Proc Natl Acad Sci USA 68:820–823PubMedGoogle Scholar
  15. 15.
    Ess KC (2006) The neurobiology of tuberous sclerosis complex. Semin Pediatr Neurol 13:37–42PubMedGoogle Scholar
  16. 16.
    Green AJ, Smith M, Yates JRW (1994) Loss of heterozygosity on chromosome 16p13.3 in hamartomas from tuberous sclerosis patients. Nat Genet 6:193–196PubMedGoogle Scholar
  17. 17.
    Henske EP, Scheithauer BW, Short MP et al (1996) Allelic loss is frequent in tuberous sclerosis kidney lesions but rare in brain lesions. Am J Hum Genet 59:400–406PubMedGoogle Scholar
  18. 18.
    Sepp T, Yates JR, Green AJ (1996) Loss of heterozygosity in tuberous sclerosis hamartomas. J Med Genet 33:962–964PubMedGoogle Scholar
  19. 19.
    Verhoef S, Vrtel R, van Essen T et al (1995) Somatic mosaicism and clinical variation in tuberous sclerosis complex. Lancet 345:202PubMedGoogle Scholar
  20. 20.
    Verhoef S, Bakker L, Tempelaars AM et al (1999) High rate of mosaicism in tuberous sclerosis complex. Am J Hum Genet 64:1632–1637PubMedGoogle Scholar
  21. 21.
    Rose VM, Au KS, Pollom G et al (1999) Germ-line mosaicism in tuberous sclerosis: how common? Am J Hum Genet 64:986–992PubMedGoogle Scholar
  22. 22.
    Chan JA, Zhang H, Roberts PS et al (2004) Pathogenesis of tuberous sclerosis subependymal giant cell astrocytomas: biallelic inactivation of TSC1 or TSC2 leads to mTOR activation. J Neuropathol Exp Neurol 63:1236–1242PubMedGoogle Scholar
  23. 23.
    Dabora SL, Jozwiak S, Franz DN et al (2001) 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 68:64–80PubMedGoogle Scholar
  24. 24.
    Jones AC, Shyamsundar MM, Thomas MW et al (1999) Comprehensive mutation analysis of TSC1 and TSC2 and phenotypic correlations in 150 families with tuberous sclerosis. Am J Hum Genet 64:1305–1315PubMedGoogle Scholar
  25. 25.
    Sancak O, Nellist M, Goedbloed M et al (2005) Mutational analysis of the TSC1 and TSC2 genes in a diagnostic setting: genotype-phenotype correlations and comparison of diagnostic DNA techniques in tuberous sclerosis complex. Eur J Hum Genet 13:731–741PubMedGoogle Scholar
  26. 26.
    Jozwiak J, Jozwiak S, Wlodarski P (2008) Possible mechanisms of disease development in tuberous sclerosis. Lancet Oncol 9:73–79PubMedGoogle Scholar
  27. 27.
    Ma L, Chen Z, Erdjument-Bromage H et al (2005) Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis. Cell 121:179–193PubMedGoogle Scholar
  28. 28.
    Jozwiak J, Grajkowska W, Kotulska K et al (2007) Brain tumor formation in tuberous sclerosis depends on Erk activation. Neuromolecular Med 9:117–127PubMedGoogle Scholar
  29. 29.
    Ma L, Teruya-Feldstein J, Bonner P et al (2007) Identification of S664 TSC2 phosphorylation as a marker for extracellular signal-regulated kinase mediated mTOR activation in tuberous sclerosis and human cancer. Cancer Res 67:7106–7112PubMedGoogle Scholar
  30. 30.
    Online Mendelian Inheritance in Man (OMIM) (2008) #191100. Tuberous sclerosis. Johns Hopkins University, Baltimore, MD. http://www.ncbi.nlm.nih.gov/entrez/dispomim.cgi?id=191100. Cited 3-Mar-2008
  31. 31.
    Jozwiak S, Schwartz RA, Janniger CK et al (1998) Skin lesions in children with tuberous sclerosis complex: their prevalence, natural course, and diagnostic significance. Int J Dermatol 37:911–917PubMedGoogle Scholar
  32. 32.
    Sun XF, Yan CL, Fang L et al (2005) Cutaneous lesions and visceral involvement of tuberous sclerosis. Chin Med J (Engl) 118:215–219Google Scholar
  33. 33.
    Sanchez NP, Wick MR, Perry HO (1981) Adenoma sebaceum of Pringle: a clinicopathologic review, with a discussion of related pathologic entities. J Cutan Pathol 8:395–403PubMedGoogle Scholar
  34. 34.
    Roach ES, Sparagana SP (2004) Diagnosis of tuberous sclerosis complex. J Child Neurol 19:643–649PubMedGoogle Scholar
  35. 35.
    Rosser T, Panigrahy A, McClintock W (2006) The diverse clinical manifestations of tuberous sclerosis complex: a review. Semin Pediatr Neurol 13:27–36PubMedGoogle Scholar
  36. 36.
    Wiznitzer M (2004) Autism and tuberous sclerosis. J Child Neurol 19:675–679PubMedGoogle Scholar
  37. 37.
    Altman NR, Purser RK, Post MJ (1988) Tuberous sclerosis: characteristics at CT and MR imaging. Radiology 167:527–532PubMedGoogle Scholar
  38. 38.
    Nixon JR, Houser OW, Gomez MR et al (1989) Cerebral tuberous sclerosis: MR imaging. Radiology 170:869–873PubMedGoogle Scholar
  39. 39.
    Baron Y, Barkovich AJ (1999) MR imaging of tuberous sclerosis in neonates and young infants. AJNR 20:907–916PubMedGoogle Scholar
  40. 40.
    Jurkiewicz E, Jozwiak S, Bekiesinska-Figatowska M et al (2006) Cyst-like cortical tubers in patients with tuberous sclerosis complex: MR imaging with the FLAIR sequence. Pediatr Radiol 36:498–501PubMedGoogle Scholar
  41. 41.
    Mizuno S, Takahashi Y, Kato Z et al (2000) Magnetic resonance spectroscopy of tubers in patients with tuberous sclerosis. Acta Neurol Scand 102:175–178PubMedGoogle Scholar
  42. 42.
    Mukonoweshuro W, Wilkinson ID, Griffiths PD (2001) Proton MR spectroscopy of cortical tubers in adults with tuberous sclerosis complex. AJNR 22:1920–1925PubMedGoogle Scholar
  43. 43.
    Karadag D, Mentzel HJ, Gullmar D et al (2005) Diffusion tensor imaging in children and adolescents with tuberous sclerosis. Pediatr Radiol 35:980–983PubMedGoogle Scholar
  44. 44.
    Jansen FE, Braun KP, van Nieuwenhuizen O et al (2003) Diffusion-weighted magnetic resonance imaging and identification of the epileptogenic tuber in patients with tuberous sclerosis. Arch Neurol 60:1580–1584PubMedGoogle Scholar
  45. 45.
    Luat AF, Makki M, Chugani HT (2007) Neuroimaging in tuberous sclerosis complex. Curr Opin Neurol 20:142–150PubMedGoogle Scholar
  46. 46.
    Chandra PS, Salamon N, Huang J et al (2006) FDG-PET/MRI coregistration and diffusion-tensor imaging distinguish epileptogenic tubers and cortex in patients with tuberous sclerosis complex: a preliminary report. Epilepsia 47:1543–1549PubMedGoogle Scholar
  47. 47.
    Kagawa K, Chugani DC, Asano E et al (2005) Epilepsy surgery outcome in children with tuberous sclerosis complex evaluated with alpha-[11C]methyl-L-tryptophan positron emission tomography (PET). J Child Neurol 20:429–438PubMedGoogle Scholar
  48. 48.
    Kamimura T, Tohyama J, Oishi M et al (2006) Magnetoencephalography in patients with tuberous sclerosis and localization-related epilepsy. Epilepsia 47:991–997PubMedGoogle Scholar
  49. 49.
    Iida K, Otsubo H, Mohamed IS et al (2005) Characterizing magnetoencephalographic spike sources in children with tuberous sclerosis complex. Epilepsia 46:1510–1517PubMedGoogle Scholar
  50. 50.
    Iwasaki S, Nakagawa H, Kichikawa K et al (1990) MR and CT of tuberous sclerosis: linear abnormalities in the cerebral white matter. AJNR 11:1029–1034PubMedGoogle Scholar
  51. 51.
    Braffman BH, Bilaniuk LT, Naidich TP et al (1992) MR imaging of tuberous sclerosis: pathogenesis of this phakomatosis, use of gadopentetate dimeglumine, and literature review. Radiology 183:227–238PubMedGoogle Scholar
  52. 52.
    Bernauer TA (1999) The radial bands sign. Radiology 212:761–762PubMedGoogle Scholar
  53. 53.
    Van Tassel P, Cure JK, Holden KR (1997) Cystlike white matter lesions in tuberous sclerosis. AJNR 18:1367–1373PubMedGoogle Scholar
  54. 54.
    Kim SK, Wang KC, Cho BK et al (2001) Biological behavior and tumorigenesis of subependymal giant cell astrocytomas. J Neurooncol 52:217–225PubMedGoogle Scholar
  55. 55.
    Goh S, Butler W, Thiele EA (2004) Subependymal giant cell tumors in tuberous sclerosis complex. Neurology 63:1457–1461PubMedGoogle Scholar
  56. 56.
    Clarke MJ, Foy AB, Wetjen N et al (2006) Imaging characteristics and growth of subependymal giant cell astrocytomas. Neurosurg Focus 20:E5PubMedGoogle Scholar
  57. 57.
    Nabbout R, Santos M, Rolland Y et al (1999) Early diagnosis of subependymal giant cell astrocytoma in children with tuberous sclerosis. J Neurol Neurosurg Psychiatry 66:370–375PubMedGoogle Scholar
  58. 58.
    Kleymenova E, Ibraghimov-Beskrovnaya O, Kugoh H et al (2001) Tuberin-dependent membrane localization of polycystin-1: a functional link between polycystic kidney disease and the TSC2 tumor suppressor gene. Mol Cell 7:823–832PubMedGoogle Scholar
  59. 59.
    Culty T, Molinie V, Lebret T et al (2006) TSC2/PKD1 contiguous gene syndrome in an adult. Minerva Urol Nefrol 58:351–354PubMedGoogle Scholar
  60. 60.
    Henske EP (2005) Tuberous sclerosis and the kidney: from mesenchyme to epithelium, and beyond. Pediatr Nephrol 20:854–857PubMedGoogle Scholar
  61. 61.
    Reeders ST, Breuning MH, Davies KE et al (1985) A highly polymorphic DNA marker linked to adult polycystic kidney disease on chromosome 16. Nature 317:542–544PubMedGoogle Scholar
  62. 62.
    Casper KA, Donnelly LF, Chen B et al (2002) Tuberous sclerosis complex: renal imaging findings. Radiology 225:451–456PubMedGoogle Scholar
  63. 63.
    Ewalt DH, Diamond N, Rees C et al (2005) Long-term outcome of transcatheter embolization of renal angiomyolipomas due to tuberous sclerosis complex. J Urol 174:1764–1766PubMedGoogle Scholar
  64. 64.
    Wagner BJ, Wong-You-Cheong JJ, Davis CJ Jr (1997) Adult renal hamartomas. Radiographics 17:155–169PubMedGoogle Scholar
  65. 65.
    Cook JD, Davis BJ, Cai SL et al (2005) Interaction between genetic susceptibility and early-life environmental exposure determines tumor-suppressor-gene penetrance. Proc Natl Acad Sci USA 102:8644–8649PubMedGoogle Scholar
  66. 66.
    Yamakado K, Tanaka N, Nakagawa T et al (2002) Renal angiomyolipoma: relationships between tumor size, aneurysm formation, and rupture. Radiology 225:78–82PubMedGoogle Scholar
  67. 67.
    Dickinson M, Ruckle H, Beaghler M et al (1998) Renal angiomyolipoma: optimal treatment based on size and symptoms. Clin Nephrol 49:281–286PubMedGoogle Scholar
  68. 68.
    Harabayashi T, Shinohara N, Katano H et al (2004) Management of renal angiomyolipomas associated with tuberous sclerosis complex. J Urol 171:102–105PubMedGoogle Scholar
  69. 69.
    Kang M, Khandelwal N, Lal A et al (2007) CT angiography in renal angiomyolipomas. Abdom Imaging 32:772–774Google Scholar
  70. 70.
    Logue LG, Acker RE, Sienko AE (2003) Best cases from the AFIP: angiomyolipomas in tuberous sclerosis. Radiographics 23:241–246PubMedGoogle Scholar
  71. 71.
    Kim JK, Park SY, Shon JH et al (2004) Angiomyolipoma with minimal fat: differentiation from renal cell carcinoma at biphasic helical CT. Radiology 230:677–684PubMedGoogle Scholar
  72. 72.
    Ren N, Qin LX, Tang ZY et al (2003) Diagnosis and treatment of hepatic angiomyolipoma in 26 cases. World J Gastroenterol 9:1856–1858PubMedGoogle Scholar
  73. 73.
    Tseng CA, Pan YS, Su YC et al (2004) Extrarenal retroperitoneal angiomyolipoma: case report and review of the literature. Abdom Imaging 29:721–723PubMedGoogle Scholar
  74. 74.
    Kandt RS, Haines JL, Smith M et al (1992) Linkage of an important gene locus for tuberous sclerosis to a chromosome 16 marker for polycystic kidney disease. Nat Genet 2:37–41PubMedGoogle Scholar
  75. 75.
    Al-Saleem T, Wessner LL, Scheithauer BW et al (1998) Malignant tumors of the kidney, brain, and soft tissues in children and young adults with the tuberous sclerosis complex. Cancer 83:2208–2216PubMedGoogle Scholar
  76. 76.
    Bjornsson J, Short MP, Kwiatkowski DJ et al (1996) Tuberous sclerosis-associated renal cell carcinoma. Clinical, pathological, and genetic features. Am J Pathol 149:1201–1208PubMedGoogle Scholar
  77. 77.
    Henske EP (2004) The genetic basis of kidney cancer: why is tuberous sclerosis complex often overlooked? Curr Mol Med 4:825–831PubMedGoogle Scholar
  78. 78.
    Fletcher CDM, Unni KK, Mertens F et al (2002) Pathology and genetics of tumours of soft tissue and bone. World Health Organization classification of tumours. IARC Press, Lyon, p 427Google Scholar
  79. 79.
    Hornick JL, Fletcher CD (2006) PEComa: what do we know so far? Histopathology 48:75–82PubMedGoogle Scholar
  80. 80.
    Flieder DB, Travis WD (1997) Clear cell “sugar” tumor of the lung: association with lymphangioleiomyomatosis and multifocal micronodular pneumocyte hyperplasia in a patient with tuberous sclerosis. Am J Surg Pathol 21:1242–1247PubMedGoogle Scholar
  81. 81.
    Pan CC, Chung MY, Ng KF et al (2007) Constant allelic alteration on chromosome 16p (TSC2 gene) in perivascular epithelioid cell tumour (PEComa): genetic evidence for the relationship of PEComa with angiomyolipoma. J Pathol 214:387–393Google Scholar
  82. 82.
    Bonetti F, Martignoni G, Colato C et al (2001) Abdominopelvic sarcoma of perivascular epithelioid cells. Report of four cases in young women, one with tuberous sclerosis. Mod Pathol 14:563–568PubMedGoogle Scholar
  83. 83.
    Folpe AL, Mentzel T, Lehr HA et al (2005) Perivascular epithelioid cell neoplasms of soft tissue and gynecologic origin: a clinicopathologic study of 26 cases and review of the literature. Am J Surg Pathol 29:1558–1575PubMedGoogle Scholar
  84. 84.
    Armah HB, Parwani AV (2007) Malignant perivascular epithelioid cell tumor (PEComa) of the uterus with late renal and pulmonary metastases: a case report with review of the literature. Diagn Pathol 2:45PubMedGoogle Scholar
  85. 85.
    Folpe AL, Goodman ZD, Ishak KG et al (2000) Clear cell myomelanocytic tumor of the falciform ligament/ligamentum teres: a novel member of the perivascular epithelioid clear cell family of tumors with a predilection for children and young adults. Am J Surg Pathol 24:1239–1246PubMedGoogle Scholar
  86. 86.
    Hancock E, Osborne J (2002) Lymphangioleiomyomatosis: a review of the literature. Respir Med 96:1–6PubMedGoogle Scholar
  87. 87.
    Hancock E, Tomkins S, Sampson J et al (2002) Lymphangioleiomyomatosis and tuberous sclerosis. Respir Med 96:7–13PubMedGoogle Scholar
  88. 88.
    Avila NA, Kelly JA, Chu SC et al (2000) Lymphangioleiomyomatosis: abdominopelvic CT and US findings. Radiology 216:147–153PubMedGoogle Scholar
  89. 89.
    Sherrier RH, Chiles C, Roggli V (1989) Pulmonary lymphangioleiomyomatosis: CT findings. AJR 153:937–940PubMedGoogle Scholar
  90. 90.
    Boehler A, Speich R, Russi EW et al (1996) Lung transplantation for lymphangioleiomyomatosis. N Engl J Med 335:1275–1280PubMedGoogle Scholar
  91. 91.
    Carsillo T, Astrinidis A, Henske EP (2000) Mutations in the tuberous sclerosis complex gene TSC2 are a cause of sporadic pulmonary lymphangioleiomyomatosis. Proc Natl Acad Sci USA 97:6085–6090PubMedGoogle Scholar
  92. 92.
    Sato T, Seyama K, Fujii H et al (2002) Mutation analysis of the TSC1 and TSC2 genes in Japanese patients with pulmonary lymphangioleiomyomatosis. J Hum Genet 47:20–28PubMedGoogle Scholar
  93. 93.
    Avila NA, Dwyer AJ, Rabel A et al (2007) Sporadic lymphangioleiomyomatosis and tuberous sclerosis complex with lymphangioleiomyomatosis: comparison of CT features. Radiology 242:277–285PubMedGoogle Scholar
  94. 94.
    Henske EP (2003) Metastasis of benign tumor cells in tuberous sclerosis complex. Genes Chromosomes Cancer 38:376–381PubMedGoogle Scholar
  95. 95.
    Karbowniczek M, Astrinidis A, Balsara BR et al (2003) Recurrent lymphangiomyomatosis after transplantation: genetic analyses reveal a metastatic mechanism. Am J Respir Crit Care Med 167:976–982PubMedGoogle Scholar
  96. 96.
    Yu J, Astrinidis A, Henske EP (2001) Chromosome 16 loss of heterozygosity in tuberous sclerosis and sporadic lymphangiomyomatosis. Am J Respir Crit Care Med 164:1537–1540PubMedGoogle Scholar
  97. 97.
    Strizheva GD, Carsillo T, Kruger WD et al (2001) The spectrum of mutations in TSC1 and TSC2 in women with tuberous sclerosis and lymphangiomyomatosis. Am J Respir Crit Care Med 163:253–258PubMedGoogle Scholar
  98. 98.
    Logginidou H, Ao X, Russo I et al (2000) Frequent estrogen and progesterone receptor immunoreactivity in renal angiomyolipomas from women with pulmonary lymphangioleiomyomatosis. Chest 117:25–30PubMedGoogle Scholar
  99. 99.
    Abbott GF, Rosado-de-Christenson ML, Frazier AA et al (2005) From the archives of the AFIP: lymphangioleiomyomatosis: radiologic-pathologic correlation. Radiographics 25:803–828PubMedGoogle Scholar
  100. 100.
    Torres VE, Bjornsson J, King BF et al (1995) Extrapulmonary lymphangioleiomyomatosis and lymphangiomatous cysts in tuberous sclerosis complex. Mayo Clin Proc 70:641–648PubMedCrossRefGoogle Scholar
  101. 101.
    Beghetti M, Gow RM, Haney I et al (1997) Pediatric primary benign cardiac tumors: a 15-year review. Am Heart J 134:1107–1114PubMedGoogle Scholar
  102. 102.
    Grebenc ML, Rosado de Christenson ML, Burke AP et al (2000) Primary cardiac and pericardial neoplasms: radiologic-pathologic correlation. Radiographics 20:1073–1103; quiz 1110–1111, 1112PubMedGoogle Scholar
  103. 103.
    Bosi G, Lintermans JP, Pellegrino PA et al (1996) The natural history of cardiac rhabdomyoma with and without tuberous sclerosis. Acta Paediatr 85:928–931PubMedGoogle Scholar
  104. 104.
    Carrico A, Moura C, Baptista MJ et al (2001) Cardiac rhabdomyomas presenting in neonates. Rev Port Cardiol 20:1095–1101PubMedGoogle Scholar
  105. 105.
    Jozwiak S, Kotulska K, Kasprzyk-Obara J et al (2006) Clinical and genotype studies of cardiac tumors in 154 patients with tuberous sclerosis complex. Pediatrics 118:e1146–e1151PubMedGoogle Scholar
  106. 106.
    Yu K, Liu Y, Wang H et al (2007) Epidemiological and pathological characteristics of cardiac tumors: a clinical study of 242 cases. Interact Cardiovasc Thorac Surg 6:636–639PubMedGoogle Scholar
  107. 107.
    Piazza N, Chughtai T, Toledano K et al (2004) Primary cardiac tumours: eighteen years of surgical experience on 21 patients. Can J Cardiol 20:1443–1448PubMedGoogle Scholar
  108. 108.
    Thomas-de-Montpreville V, Nottin R, Dulmet E et al (2007) Heart tumors in children and adults: clinicopathological study of 59 patients from a surgical center. Cardiovasc Pathol 16:22–28PubMedGoogle Scholar
  109. 109.
    Isaacs H Jr (2004) Fetal and neonatal cardiac tumors. Pediatr Cardiol 25:252–273PubMedGoogle Scholar
  110. 110.
    Shimizu M, Manabe T, Tazelaar HD et al (1994) Intramyocardial angiomyolipoma. Am J Surg Pathol 18:1164–1169PubMedGoogle Scholar
  111. 111.
    Tsai CC, Chou CY, Han SJ et al (1997) Cardiac angiomyolipoma: radiologic and pathologic correlation. J Formos Med Assoc 96:653–656PubMedGoogle Scholar
  112. 112.
    Winterkorn EB, Dodd JD, Inglessis I et al (2007) Tuberous sclerosis complex and myocardial fat-containing lesions: a report of four cases. Clin Genet 71:371–373PubMedGoogle Scholar
  113. 113.
    Green GJ (1968) The radiology of tuberose sclerosis. Clin Radiol 19:135–147PubMedGoogle Scholar
  114. 114.
    Holt JF, Dickerson WW (1952) The osseous lesions of tuberous sclerosis. Radiology 58:1–8PubMedGoogle Scholar
  115. 115.
    Jost CJ, Gloviczki P, Edwards WD et al (2001) Aortic aneurysms in children and young adults with tuberous sclerosis: report of two cases and review of the literature. J Vasc Surg 33:639–642PubMedGoogle Scholar
  116. 116.
    Restrepo R, Ranson M, Chait PG et al (2003) Extracranial aneurysms in children: practical classification and correlative imaging. AJR 181:867–878PubMedGoogle Scholar
  117. 117.
    Rolfes DB, Towbin R, Bove KE (1985) Vascular dysplasia in a child with tuberous sclerosis. Pediatr Pathol 3:359–373PubMedGoogle Scholar
  118. 118.
    Burrows NJ, Johnson SR (2004) Pulmonary artery aneurysm and tuberous sclerosis. Thorax 59:86PubMedGoogle Scholar
  119. 119.
    Hagood CO Jr, Garvin DD, Lachina FM et al (1976) Abdominal aortic aneurysm and renal hamartoma in an infant with tuberous sclerosis. Surgery 79:713–715PubMedGoogle Scholar
  120. 120.
    Tamisier D, Goutiere F, Sidi D et al (1997) Abdominal aortic aneurysm in a child with tuberous sclerosis. Ann Vasc Surg 11:637–639PubMedGoogle Scholar
  121. 121.
    Beall S, Delaney P (1983) Tuberous sclerosis with intracranial aneurysm. Arch Neurol 40:826–827PubMedGoogle Scholar
  122. 122.
    Brill CB, Peyster RG, Hoover ED et al (1985) Giant intracranial aneurysm in a child with tuberous sclerosis: CT demonstration. J Comput Assist Tomogr 9:377–380PubMedGoogle Scholar
  123. 123.
    Jurkiewicz E, Jozwiak S (2006) Giant intracranial aneurysm in a 9-year-old boy with tuberous sclerosis. Pediatr Radiol 36:463PubMedGoogle Scholar
  124. 124.
    Chatrath R, Noronha PA (2000) Intracranial aneurysm in tuberous sclerosis. Int Pediatr 15:152–154Google Scholar
  125. 125.
    Beltramello A, Puppini G, Bricolo A et al (1999) Does the tuberous sclerosis complex include intracranial aneurysms? A case report with a review of the literature. Pediatr Radiol 29:206–211PubMedGoogle Scholar
  126. 126.
    Huang S, Bjornsti MA, Houghton PJ (2003) Rapamycins: mechanism of action and cellular resistance. Cancer Biol Ther 2:222–232PubMedGoogle Scholar
  127. 127.
    Franz DN, Leonard J, Tudor C et al (2006) Rapamycin causes regression of astrocytomas in tuberous sclerosis complex. Ann Neurol 59:490–498PubMedGoogle Scholar
  128. 128.
    Herry I, Neukirch C, Debray MP et al (2007) Dramatic effect of sirolimus on renal angiomyolipomas in a patient with tuberous sclerosis complex. Eur J Intern Med 18:76–77PubMedGoogle Scholar
  129. 129.
    Lee L, Sudentas P, Donohue B et al (2005) Efficacy of a rapamycin analog (CCI-779) and IFN-gamma in tuberous sclerosis mouse models. Genes Chromosomes Cancer 42:213–227PubMedGoogle Scholar
  130. 130.
    Bissler JJ, McCormack FX, Young LR et al (2008) Sirolimus for angiomyolipoma in tuberous sclerosis complex or lymphangioleiomyomatosis. N Engl J Med 358:140–151PubMedGoogle Scholar
  131. 131.
    Roach ES, Gomez MR, Northrup H (1998) Tuberous sclerosis complex consensus conference: revised clinical diagnostic criteria. J Child Neurol 13:624–628PubMedGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Department of RadiologyCincinnati Children’s Medical CenterCincinnatiUSA

Personalised recommendations