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[[Image:Angiomyolipoma -- low mag.jpg|thumb|right|[[Micrograph]] showing a renal [[angiomyolipoma]], as may be seen in tuberous sclerosis. [[H&E stain]]. (WC/KGH)]] | |||
'''Tuberous sclerosis''', also '''tuberous sclerosis complex''' (abbreviated '''TSC'''), is an autosomal dominant [[syndrome]] associated with an increased risk of [[hamartoma]]s and some risk increase for malignant tumours. | '''Tuberous sclerosis''', also '''tuberous sclerosis complex''' (abbreviated '''TSC'''), is an autosomal dominant [[syndrome]] associated with an increased risk of [[hamartoma]]s and some risk increase for malignant tumours. | ||
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#Mental retardation. | #Mental retardation. | ||
#Adenoma sebaceum ([[angiofibroma]]s). | #Adenoma sebaceum ([[angiofibroma]]s). | ||
Diagnostic consensus criteria [http://www.pedneur.com/article/S0887-8994%2813%2900490-6/pdf published] (2012, OpenAcess). | |||
Also called ''Bourneville-Pringle disease''. | |||
==General== | ==General== | ||
*Autosomal dominant with variable penetrance.<ref name=pmid25093518/> | *Autosomal dominant with variable penetrance.<ref name=pmid25093518/> | ||
*Majority (60-70%) are ''de novo'' mutations.<ref name=pmid25093518/> | *Majority (60-70%) are ''de novo'' mutations.<ref name=pmid25093518/> | ||
*May be treated with a mTOR inhibitor, e.g. [[everolimus]].<ref name=pmid23413089>{{Cite journal | last1 = Pirson | first1 = Y. | title = Tuberous sclerosis complex-associated kidney angiomyolipoma: from contemplation to action. | journal = Nephrol Dial Transplant | volume = 28 | issue = 7 | pages = 1680-5 | month = Jul | year = 2013 | doi = 10.1093/ndt/gft009 | PMID = 23413089 }}</ref> | |||
==Associations== | ==Associations== | ||
Pathologic: | Pathologic: | ||
*Renal [[angiomyolipoma]]. | *Renal [[angiomyolipoma]]. | ||
** | **Represent approximately 85% of renal lesions in individuals with TSC.<ref name=pmid25093518>{{Cite journal | last1 = Guo | first1 = J. | last2 = Tretiakova | first2 = MS. | last3 = Troxell | first3 = ML. | last4 = Osunkoya | first4 = AO. | last5 = Fadare | first5 = O. | last6 = Sangoi | first6 = AR. | last7 = Shen | first7 = SS. | last8 = Lopez-Beltran | first8 = A. | last9 = Mehra | first9 = R. | title = Tuberous Sclerosis-associated Renal Cell Carcinoma: A Clinicopathologic Study of 57 Separate Carcinomas in 18 Patients. | journal = Am J Surg Pathol | volume = 38 | issue = 11 | pages = 1457-67 | month = Nov | year = 2014 | doi = 10.1097/PAS.0000000000000248 | PMID = 25093518 }}</ref><ref name=pmid17003820>{{cite journal |author=Rakowski SK, Winterkorn EB, Paul E, Steele DJ, Halpern EF, Thiele EA |title=Renal manifestations of tuberous sclerosis complex: Incidence, prognosis, and predictive factors |journal=Kidney Int. |volume=70 |issue=10 |pages=1777–82 |year=2006 |month=November |pmid=17003820 |doi=10.1038/sj.ki.5001853 |url=}}</ref> | ||
*Cardiac [[rhabdomyoma]]. | *Cardiac [[rhabdomyoma]]. | ||
*[[Lymphangiomyomatosis]]. | *[[Lymphangiomyomatosis]]. | ||
**Seen in ~1/3 of females with TSC in one series.<ref name=pmid17003820/> | |||
*[[Subependymal giant cell astrocytoma]] (SEGA).<ref name=pmid21455842>{{Cite journal | last1 = Grajkowska | first1 = W. | last2 = Kotulska | first2 = K. | last3 = Jurkiewicz | first3 = E. | last4 = Roszkowski | first4 = M. | last5 = Daszkiewicz | first5 = P. | last6 = Jóźwiak | first6 = S. | last7 = Matyja | first7 = E. | title = Subependymal giant cell astrocytomas with atypical histological features mimicking malignant gliomas. | journal = Folia Neuropathol | volume = 49 | issue = 1 | pages = 39-46 | month = | year = 2011 | doi = | PMID = 21455842 }}</ref> | *[[Subependymal giant cell astrocytoma]] (SEGA).<ref name=pmid21455842>{{Cite journal | last1 = Grajkowska | first1 = W. | last2 = Kotulska | first2 = K. | last3 = Jurkiewicz | first3 = E. | last4 = Roszkowski | first4 = M. | last5 = Daszkiewicz | first5 = P. | last6 = Jóźwiak | first6 = S. | last7 = Matyja | first7 = E. | title = Subependymal giant cell astrocytomas with atypical histological features mimicking malignant gliomas. | journal = Folia Neuropathol | volume = 49 | issue = 1 | pages = 39-46 | month = | year = 2011 | doi = | PMID = 21455842 }}</ref> | ||
**Usu at. thalamo-striatal sulcus of the lateral ventricle. | |||
**Contrast enhancement and progressive growth. | |||
**Precursor: Subependymal nodules (SENs) without enhancement. | |||
*Renal cysts.<ref name=pmid25093518/> | *Renal cysts.<ref name=pmid25093518/> | ||
**Seen in ~45% of individuals with TSC in one series, no gender bias.<ref name=pmid17003820/> | |||
*[[Tuberous sclerosis-associated renal cell carcinoma]] - an evolving entity.<ref name=pmid25093518/> | *[[Tuberous sclerosis-associated renal cell carcinoma]] - an evolving entity.<ref name=pmid25093518/> | ||
*[[Multifocal micronodular pneumocyte hyperplasia associated with tuberous sclerosis|Multifocal micronodular pneumocyte hyperplasia]]<ref name=pmid15841738>{{Cite journal | last1 = Kobayashi | first1 = T. | last2 = Satoh | first2 = K. | last3 = Ohkawa | first3 = M. | title = Multifocal micronodular pneumocyte hyperplasia associated with tuberous sclerosis. | journal = Acta Radiol | volume = 46 | issue = 1 | pages = 37-40 | month = Feb | year = 2005 | doi = | PMID = 15841738 }}</ref> - may mimic [[atypical adenomatous hyperplasia of the lung|atypical adenomatous hyperplasia]].<ref name=pmid18535095>{{Cite journal | last1 = Kobashi | first1 = Y. | last2 = Sugiu | first2 = T. | last3 = Mouri | first3 = K. | last4 = Irei | first4 = T. | last5 = Nakata | first5 = M. | last6 = Oka | first6 = M. | title = Multifocal micronodular pneumocyte hyperplasia associated with tuberous sclerosis: differentiation from multiple atypical adenomatous hyperplasia. | journal = Jpn J Clin Oncol | volume = 38 | issue = 6 | pages = 451-4 | month = Jun | year = 2008 | doi = 10.1093/jjco/hyn042 | PMID = 18535095 }}</ref> | |||
*[[Cortical tuber]]s (malformative, epilepsy-associated).<ref>{{Cite journal | last1 = Cotter | first1 = JA. | title = An update on the central nervous system manifestations of tuberous sclerosis complex. | journal = Acta Neuropathol | volume = | issue = | pages = | month = Apr | year = 2019 | doi = 10.1007/s00401-019-02003-1 | PMID = 30976976 }}</ref> | |||
Note: | Note: | ||
*The same genes (TSC1, TSC2) are implicated in [[PEComa]]s. | *The same genes (TSC1, TSC2) are implicated in [[PEComa]]s. | ||
*Renal lesions are seen in ~60% of patients.<ref name=pmid17003820/> | |||
[[File:TSC.png|thumb300px]] | |||
*Scheme illustrates types of neuropathologic changes in tuberous sclerosis complex. 1- isolated balloon cells in white matter, TSC-/-; 2- heterotopic cluster with dysplastic neurons TSC-/+; 3- subependymal nodules and 4- subependymal giant cell astrocytoma in ependyma of third ventricle (note that this is not usual localisation for both lesions, which is rather ependyma of lateral ventricles) 5- cortical tuber; 6 - linear migration streak. This scheme is based on DiMario, F Brain abnormalities in Tuberous Sclerosis Complex J Child Neurol, 9, 650-657. 2004.<ref>{{Cite journal | last1 = DiMario | first1 = FJ. | title = Brain abnormalities in tuberous sclerosis complex. | journal = J Child Neurol | volume = 19 | issue = 9 | pages = 650-7 | month = Sep | year = 2004 | doi = 10.1177/08830738040190090401 | PMID = 15563010 }}</ref> | |||
Mnemonic '''SALSA HEART''':<ref>URL: [http://www.usmle-forums.com/usmle-step-1-mnemonics/303-tuberous-sclerosis.html http://www.usmle-forums.com/usmle-step-1-mnemonics/303-tuberous-sclerosis.html]. Accessed on: 20 October 2011.</ref> | Mnemonic '''SALSA HEART''':<ref>URL: [http://www.usmle-forums.com/usmle-step-1-mnemonics/303-tuberous-sclerosis.html http://www.usmle-forums.com/usmle-step-1-mnemonics/303-tuberous-sclerosis.html]. Accessed on: 20 October 2011.</ref> | ||
*'''S'''hagreen patches. | *'''S'''hagreen patches. | ||
**Shagreen patch = ''connective-tissue nevus'' composed of collagen, i.e. ''collagenoma''.<ref>URL: [http://dermatology-s10.cdlib.org/1611/articles/3_2009-11-17/batra.html http://dermatology-s10.cdlib.org/1611/articles/3_2009-11-17/batra.html]. Accessed on: 18 February 2012.</ref> | **Shagreen patch = ''connective-tissue nevus'' composed of collagen, i.e. ''collagenoma''.<ref>URL: [http://dermatology-s10.cdlib.org/1611/articles/3_2009-11-17/batra.html http://dermatology-s10.cdlib.org/1611/articles/3_2009-11-17/batra.html]. Accessed on: 18 February 2012.</ref> | ||
*'''A'''sh | *'''A'''sh-leaf spots. | ||
*'''S'''EGA. | **Hypopigmented [[macule]]s.<ref name=pmid23761491>{{Cite journal | last1 = Jindal | first1 = R. | last2 = Jain | first2 = A. | last3 = Gupta | first3 = A. | last4 = Shirazi | first4 = N. | title = Ash-leaf spots or naevus depigmentosus: a diagnostic challenge. | journal = BMJ Case Rep | volume = 2013 | issue = | pages = | month = Jun | year = 2013 | doi = 10.1136/bcr-2012-007008 | PMID = 23761491 }}</ref> | ||
*[[Lymphangioleiomyomatosis]]. | |||
*[[Subependymal giant cell astrocytoma|'''S'''EGA]]. | |||
*[[angiofibroma|'''A'''ngiofibroma]]. | *[[angiofibroma|'''A'''ngiofibroma]]. | ||
*[[hamartoma|'''H'''amartomas]]. | *[[hamartoma|'''H'''amartomas]]. | ||
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*TSC2.<ref>{{OMIM|191092}}</ref> | *TSC2.<ref>{{OMIM|191092}}</ref> | ||
**Some evidence to suggest it is more often implicated in malignant tumours (than TSC1).<ref name=pmid9827727>{{cite journal |author=Al-Saleem T, Wessner LL, Scheithauer BW, ''et al.'' |title=Malignant tumors of the kidney, brain, and soft tissues in children and young adults with the tuberous sclerosis complex |journal=Cancer |volume=83 |issue=10 |pages=2208–16 |year=1998 |month=November |pmid=9827727 |doi= |url=}}</ref> | **Some evidence to suggest it is more often implicated in malignant tumours (than TSC1).<ref name=pmid9827727>{{cite journal |author=Al-Saleem T, Wessner LL, Scheithauer BW, ''et al.'' |title=Malignant tumors of the kidney, brain, and soft tissues in children and young adults with the tuberous sclerosis complex |journal=Cancer |volume=83 |issue=10 |pages=2208–16 |year=1998 |month=November |pmid=9827727 |doi= |url=}}</ref> | ||
**TSC2 mutations have a higher prevalence (than TSC1 mutations) and are considered more aggressive.<ref name=pmid17003820>{{cite journal |author=Rakowski SK, Winterkorn EB, Paul E, Steele DJ, Halpern EF, Thiele EA |title=Renal manifestations of tuberous sclerosis complex: Incidence, prognosis, and predictive factors |journal=Kidney Int. |volume=70 |issue=10 |pages=1777–82 |year=2006 |month=November |pmid=17003820 |doi=10.1038/sj.ki.5001853 |url=}}</ref> | |||
Notes: | |||
*The proteins (hamartin and tuberin) are expressed in a wide variety of tissues.<ref name=pmid11266527>{{Cite journal | last1 = Johnson | first1 = MW. | last2 = Kerfoot | first2 = C. | last3 = Bushnell | first3 = T. | last4 = Li | first4 = M. | last5 = Vinters | first5 = HV. | title = Hamartin and tuberin expression in human tissues. | journal = Mod Pathol | volume = 14 | issue = 3 | pages = 202-10 | month = Mar | year = 2001 | doi = 10.1038/modpathol.3880286 | PMID = 11266527 }}</ref> | |||
==Incidence== | ==Incidence== | ||
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[[Category:Syndromes]] | [[Category:Syndromes]] | ||
[[Category:Neuropathology]] | |||