Skip to main content Accessibility help

We use cookies to distinguish you from other users and to provide you with a better experience on our websites. Close this message to accept cookies or find out how to manage your cookie settings.

Close cookie message
×
Hostname: page-component-7479d7b7d-8zxtt Total loading time: 0 Render date: 2024-07-11T01:27:14.249Z Has data issue: false hasContentIssue false

Chapter 14 - Tuberous Sclerosis Complex

from Section 6 - Cystic Diseases

Published online by Cambridge University Press:  10 August 2023

By
Christie L. Boils
Edited by
Helen Liapis
Helen Liapis
Affiliation:
Ludwig Maximilian University, Nephrology Center, Munich, Adjunct Professor and Washington University St Louis, Department of Pathology and Immunology, Retired Professor
Get access

Summary

Tuberous sclerosis complex (TSC) is an autosomal dominantly inherited syndrome caused by mutations in either hamartin (TSC1 gene, chromosome 9q34) or tuberin (TSC2 gene, chromosome 16p13), leading to hamartomas, tumors, and cysts of multiple organs. The extreme variability of organ involvement and phenotypic expression, manifesting over a broad age range, makes the diagnosis of tuberous sclerosis complex challenging. The clinical diagnosis of TSC is based on the presence of major and minor features; those diagnostic features involving the kidney are angiomyolipomas and cysts, both of which are often multiple and bilateral. Angiomyolipomas range from overt to microscopic to angiomyolipomatous change of the renal parenchyma. Renal disease may be the initial or only manifestation of TSC, and absence of a family history is likely, given the high incidence of new mutations.

Keywords

Tuberous sclerosis complex (TSC)angiomyolipomarenal cystrenal microcystpolycystic kidneyangiomyolipomatous changeangiomyolipoma with epithelial-lined cyst (AMLEC)mTOR inhibitor
Type
Chapter
Information
Pediatric Nephropathology & Childhood Kidney Tumors , pp. 272 - 282
Publisher: Cambridge University Press
Print publication year: 2023

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

Au, K. S., Williams, A. T., Roach, E. S., et al. Genotype/phenotype correlation in 325 individuals referred for a diagnosis of tuberous sclerosis complex in the United States. Genet Med. 2007; 9: 88–100.CrossRefGoogle ScholarPubMed
Siroky, B. J., Yin, H., Bissler, J. J.. Clinical and molecular insights into tuberous sclerosis complex renal disease. Pediatr Nephrol. 2011; 26: 839–52.Google Scholar
Kozlowski, P., Roberts, P., Dabora, S., et al. Identification of 54 large deletions/duplications in TSC1 and TSC2 using MLPA, and genotype-phenotype correlations. Hum Genet. 2007; 121: 389–400.Google Scholar
Dabora, S. L., Jozwiak, S., Franz, D. N., 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; 68: 64–80.CrossRefGoogle Scholar
Bisceglia, M., Galliani, C., Carosi, I., et al. Tuberous sclerosis complex with polycystic kidney disease of the adult type: The TSC2/ADPKD1 contiguous gene syndrome. Int J Surg Pathol. 2008; 16: 375–85.Google Scholar
Crino, P. B., Nathanson, K. L., Henske, E. P.. The tuberous sclerosis complex. N Engl J Med. 2006; 355: 1345–56.Google Scholar
Ebrahimi-Fakhari, D., Mann, L. L., Poryo, M., et al. Incidence of tuberous sclerosis and age at first diagnosis: New data and emerging trends from a national, prospective surveillance study. Orphanet J Rare Dis. 2018; 13: 117.Google Scholar
Yates, J. R., Maclean, C., Higgins, J. N., et al. The Tuberous Sclerosis 2000 Study: Presentation, initial assessments and implications for diagnosis and management. Arch Dis Child. 2011; 96: 1020–5.Google Scholar
Peron, A., Northrup, H.. Tuberous sclerosis complex. Am J Med Genet C Semin Med Genet. 2018; 178: 274–7.Google Scholar
Marom, D.. Genetics of tuberous sclerosis complex: An update. Childs Nerv Syst. 2020; 36: 2489–96.CrossRefGoogle ScholarPubMed
Peron, A., Canevini, M. P., Ghelma, F., et al. Healthcare transition from childhood to adulthood in tuberous sclerosis complex. Am J Med Genet C Semin Med Genet. 2018; 178: 355–64.Google Scholar
Northrup, H., Krueger, D. A.. Tuberous sclerosis complex diagnostic criteria update: Recommendations of the 2012 international tuberous sclerosis complex consensus conference. Pediatr Neurol. 2013; 49: 243–54.CrossRefGoogle ScholarPubMed
Mettin, R. R., Merkenschlager, A., Bernhard, M. K., et al. Wide spectrum of clinical manifestations in children with tuberous sclerosis complex--follow-up of 20 children. Brain Dev. 2014; 36: 306–14.Google Scholar
Wilbur, C., Sanguansermsri, C., Chable, H., et al. Manifestations of tuberous sclerosis complex: The experience of a provincial clinic. Can J Neurol Sci. 2017; 44: 35–43.Google Scholar
Warncke, J. C., Brodie, K. E., Grantham, E. C., et al. Pediatric renal angiomyolipomas in tuberous sclerosis complex. J Urol. 2017; 197: 500–6.Google Scholar
Kingswood, J. C., Belousova, E., Benedik, M. P., et al. Renal angiomyolipoma in patients with tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increase disease Awareness. Nephrol Dial Transplant. 2019; 34: 502–8.Google Scholar
Bissler, J. J., Christopher Kingswood, J.. Renal manifestation of tuberous sclerosis complex. Am J Med Genet C Semin Med Genet. 2018; 178: 338–47.CrossRefGoogle ScholarPubMed
Bissler, J. J., Kingswood, J. C.. Renal angiomyolipomata. Kidney Int. 2004; 66: 924–34.Google Scholar
Guo, J., Tretiakova, M. S., Troxell, M. L., et al. Tuberous sclerosis-associated renal cell carcinoma: A clinicopathologic study of 57 separate carcinomas in 18 patients. Am J Surg Pathol. 2014; 38: 1457–67.Google Scholar
Janssens, P., Van Hoeve, K., De Waele, L., et al. Renal progression factors in young patients with tuberous sclerosis complex: A retrospective cohort study. Pediatr Nephrol. 2018; 33: 2085–93.Google Scholar
Kingswood, J. C., Nasuti, P., Patel, K., et al. The economic burden of tuberous sclerosis complex in UK patients with renal manifestations: A retrospective cohort study in the clinical practice research datalink (CPRD). J Med Econ. 2016; 19: 1116–26.CrossRefGoogle ScholarPubMed
Amin, S., Lux, A., Calder, N., et al. Causes of mortality in individuals with tuberous sclerosis complex. Dev Med Child Neurol. 2017; 59: 612–17.CrossRefGoogle ScholarPubMed
Morin, C. E., Morin, N. P., Franz, D. N., et al. Thoracoabdominal imaging of tuberous sclerosis. Pediatr Radiol. 2018; 48: 1307–23.CrossRefGoogle ScholarPubMed
Kozłowska, J., Okoń, K.. Renal tumors in postmortem material. Pol J Pathol. 2008; 59: 21–5.Google Scholar
Krueger, D. A., Northrup, H.. Tuberous sclerosis complex surveillance and management: Recommendations of the 2012 International Tuberous Sclerosis Complex Consensus Conference. Pediatr Neurol. 2013; 49: 255–65.CrossRefGoogle ScholarPubMed
Boils, C., et al. Tuberous sclerosis: The spectrum of metanephric defects, cystic kidney diseases and neoplasms in 26 pediatric and adult cases. Kidney/Renal Pathol Mod Pathol. 2014; 27: 405–16.Google Scholar
Bonsib, S. M., Boils, C., Gokden, N., et al. Tuberous sclerosis complex: Hamartin and tuberin expression in renal cysts and its discordant expression in renal neoplasms. Pathol Res Pract. 2016; 212: 972–9.CrossRefGoogle ScholarPubMed
Bernstein, J., Robbins, T. O., Kissane, J. M.. The renal lesions of tuberous sclerosis. Semin Diagn Pathol. 1986; 3: 97–105.Google Scholar
Bernstein, J., Robbins, T. O.. Renal involvement in tuberous sclerosis. Ann N Y Acad Sci. 1991; 615: 36–49.CrossRefGoogle ScholarPubMed
Martignoni, G., Bonetti, F., Pea, M., et al. Renal disease in adults with TSC2/PKD1 contiguous gene syndrome. Am J Surg Pathol. 2002; 26: 198–205.CrossRefGoogle ScholarPubMed
Bernstein, J.. Renal cystic disease in the tuberous sclerosis complex. Pediatr Nephrol. 1993; 7: 490–5.CrossRefGoogle ScholarPubMed
Fine, S. W., Reuter, V. E., Epstein, J. I., et al. Angiomyolipoma with epithelial cysts (AMLEC): A distinct cystic variant of angiomyolipoma. Am J Surg Pathol. 2006; 30: 593-9.CrossRefGoogle ScholarPubMed
Trpkov, K., Hes, O., Bonert, M., et al. Eosinophilic, solid, and cystic renal cell carcinoma: Clinicopathologic study of 16 unique, sporadic neoplasms occurring in women. Am J Surg Pathol. 2016; 40: 60–71.Google Scholar
Schreiner, A., Daneshmand, S., Bayne, A., et al. Distinctive morphology of renal cell carcinomas in tuberous sclerosis. Int J Surg Pathol. 2010; 18: 409–18.Google Scholar
Lam, H. C., Siroky, B. J., Henske, E. P.. Renal disease in tuberous sclerosis complex: Pathogenesis and therapy. Nat Rev Nephrol. 2018; 14: 704–16.Google Scholar
Roach, E. S.. Applying the lessons of tuberous sclerosis: The 2015 Hower Award Lecture. Pediatr Neurol. 2016; 63: 6–22.Google Scholar
Halpenny, D., Snow, A., McNeill, G., et al. The radiological diagnosis and treatment of renal angiomyolipoma-current status. Clin Radiol. 2010; 65: 99–108.CrossRefGoogle ScholarPubMed
Franz, D. N., Krueger, D. A.. mTOR inhibitor therapy as a disease modifying therapy for tuberous sclerosis complex. Am J Med Genet C Semin Med Genet. 2018; 178: 365–73.Google Scholar

Save book to Kindle

To save this book to your Kindle, first ensure coreplatform@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about saving to your Kindle.

Note you can select to save to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be saved to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

Find out more about the Kindle Personal Document Service.

  • Tuberous Sclerosis Complex
  • Edited by Helen Liapis, Ludwig Maximilian University, Nephrology Center, Munich, Adjunct Professor and Washington University St Louis, Department of Pathology and Immunology, Retired Professor
  • Book: Pediatric Nephropathology & Childhood Kidney Tumors
  • Online publication: 10 August 2023
  • Chapter DOI: https://doi.org/10.1017/9781108907224.015
Available formats
×

Save book to Dropbox

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Dropbox.

  • Tuberous Sclerosis Complex
  • Edited by Helen Liapis, Ludwig Maximilian University, Nephrology Center, Munich, Adjunct Professor and Washington University St Louis, Department of Pathology and Immunology, Retired Professor
  • Book: Pediatric Nephropathology & Childhood Kidney Tumors
  • Online publication: 10 August 2023
  • Chapter DOI: https://doi.org/10.1017/9781108907224.015
Available formats
×

Save book to Google Drive

To save content items to your account, please confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your account. Find out more about saving content to Google Drive.

  • Tuberous Sclerosis Complex
  • Edited by Helen Liapis, Ludwig Maximilian University, Nephrology Center, Munich, Adjunct Professor and Washington University St Louis, Department of Pathology and Immunology, Retired Professor
  • Book: Pediatric Nephropathology & Childhood Kidney Tumors
  • Online publication: 10 August 2023
  • Chapter DOI: https://doi.org/10.1017/9781108907224.015
Available formats
×