Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA)

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dc.contributor.authorSauter, Matthias
dc.contributor.authorBelousova, Elena
dc.contributor.authorBenedik, Mirjana P.
dc.contributor.authorCarter, Tom
dc.contributor.authorCottin, Vincent
dc.contributor.authorCuratolo, Paolo
dc.contributor.authorDahlin, Maria
dc.contributor.authorD’Amato, Lisa
dc.contributor.authord’Augères, Guillaume B.
dc.contributor.authorde Vries, Petrus J.
dc.contributor.authorFerreira, José C.
dc.contributor.authorFeucht, Martha
dc.contributor.authorFladrowski, Carla
dc.contributor.authorHertzberg, Christoph
dc.contributor.authorJozwiak, Sergiusz
dc.contributor.authorLawson, John A.
dc.contributor.authorMacaya, Alfons
dc.contributor.authorMarques, Ruben
dc.contributor.authorNabbout, Rima
dc.contributor.authorO’Callaghan, Finbar
dc.contributor.authorQin, Jiong
dc.contributor.authorSander, Valentin
dc.contributor.authorShah, Seema
dc.contributor.authorTakahashi, Yukitoshi
dc.contributor.authorTouraine, Renaud
dc.contributor.authorYouroukos, Sotiris
dc.contributor.authorZonnenberg, Bernard
dc.contributor.authorJansen, Anna
dc.contributor.authorKingswood, J. C.
dc.date.accessioned2021-10-08T08:40:20Z
dc.date.available2021-10-08T08:40:20Z
dc.date.issued2021-07-06
dc.date.updated2021-07-11T03:16:35Z
dc.description.abstractBackground Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant disorder caused by pathogenic variants in either the TSC1 or TSC2 gene. Common manifestations of TSC have been grouped into major and minor clinical diagnostic criteria and assessed in clinical routine workup. However, case studies point towards the existence of rare disease manifestations and to the potential association of TSC with malignant tumors. In this study we sought to characterize rare manifestations and malignancies using a large cohort of patients. Methods TuberOus SClerosis registry to increAse disease awareness (TOSCA) is a multicenter, international disease registry collecting clinical manifestations and characteristics of patients with TSC, both retrospectively and prospectively. We report rates and characteristics of rare manifestations and malignancies in patients with TSC who had enrolled in the TOSCA registry. We also examined these manifestations by age, sex, and genotype (TSC1 or TSC2). Results Overall, 2211 patients with TSC were enrolled in the study. Rare manifestations were reported in 382 (17.3%) study participants and malignancies in 65 (2.9%). Of these rare manifestations, the most frequent were bone sclerotic foci (39.5%), scoliosis (23%), thyroid adenoma (5.5%), adrenal angiomyolipoma (4.5%), hemihypertrophy and pancreatic neuroendocrine tumors (pNET; both 3.1%). These rare manifestations were more commonly observed in adults than children (66.2% vs. 22.7%), in females versus males (58.4% vs. 41.6%; except for scoliosis: 48.9% vs. 51.1%), and in those with TSC2 versus TSC1 (67.0% vs. 21.1%; except for thyroid adenoma: 42.9% vs. 57.1%). In the 65 individuals with reported malignancies, the most common were renal cell carcinoma (47.7%), followed by breast (10.8%) and thyroid cancer (9.2%). Although malignancies were more common in adult patients, 26.1% were reported in children and 63.1% in individuals < 40 years. TSC1 mutations were over-represented in individuals with malignancies compared to the overall TOSCA cohort (32.1% vs. 18.5%). Conclusion Rare manifestations were observed in a significant proportion of individuals with TSC. We recommend further examination of rare manifestations in TSC. Collectively, malignancies were infrequent findings in our cohort. However, compared to the general population, malignant tumors occurred earlier in age and some tumor types were more common.en_US
dc.identifier.apacitationSauter, M., Belousova, E., Benedik, Mirjana P., Carter, T., Cottin, V., Curatolo, P., ... Kingswood, J. C. (2021). Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA). <i>Orphanet Journal of Rare Diseases</i>, 16(Article number: 301), http://hdl.handle.net/11427/35038en_ZA
dc.identifier.chicagocitationSauter, Matthias, Elena Belousova, Mirjana P. Benedik, Tom Carter, Vincent Cottin, Paolo Curatolo, Maria Dahlin, et al "Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA)." <i>Orphanet Journal of Rare Diseases</i> 16, Article number: 301. (2021) http://hdl.handle.net/11427/35038en_ZA
dc.identifier.citationSauter, M., Belousova, E., Benedik, Mirjana P., Carter, T., Cottin, V., Curatolo, P., Dahlin, M. & et al. 2021. Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA). <i>Orphanet Journal of Rare Diseases.</i> 16(Article number: 301) http://hdl.handle.net/11427/35038en_ZA
dc.identifier.ris TY - Journal Article AU - Sauter, Matthias AU - Belousova, Elena AU - Benedik, Mirjana P. AU - Carter, Tom AU - Cottin, Vincent AU - Curatolo, Paolo AU - Dahlin, Maria AU - D’Amato, Lisa AU - d’Augères, Guillaume B. AU - de Vries, Petrus J. AU - Ferreira, José C. AU - Feucht, Martha AU - Fladrowski, Carla AU - Hertzberg, Christoph AU - Jozwiak, Sergiusz AU - Lawson, John A. AU - Macaya, Alfons AU - Marques, Ruben AU - Nabbout, Rima AU - O’Callaghan, Finbar AU - Qin, Jiong AU - Sander, Valentin AU - Shah, Seema AU - Takahashi, Yukitoshi AU - Touraine, Renaud AU - Youroukos, Sotiris AU - Zonnenberg, Bernard AU - Jansen, Anna AU - Kingswood, J. C. AB - Background Tuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant disorder caused by pathogenic variants in either the TSC1 or TSC2 gene. Common manifestations of TSC have been grouped into major and minor clinical diagnostic criteria and assessed in clinical routine workup. However, case studies point towards the existence of rare disease manifestations and to the potential association of TSC with malignant tumors. In this study we sought to characterize rare manifestations and malignancies using a large cohort of patients. Methods TuberOus SClerosis registry to increAse disease awareness (TOSCA) is a multicenter, international disease registry collecting clinical manifestations and characteristics of patients with TSC, both retrospectively and prospectively. We report rates and characteristics of rare manifestations and malignancies in patients with TSC who had enrolled in the TOSCA registry. We also examined these manifestations by age, sex, and genotype (TSC1 or TSC2). Results Overall, 2211 patients with TSC were enrolled in the study. Rare manifestations were reported in 382 (17.3%) study participants and malignancies in 65 (2.9%). Of these rare manifestations, the most frequent were bone sclerotic foci (39.5%), scoliosis (23%), thyroid adenoma (5.5%), adrenal angiomyolipoma (4.5%), hemihypertrophy and pancreatic neuroendocrine tumors (pNET; both 3.1%). These rare manifestations were more commonly observed in adults than children (66.2% vs. 22.7%), in females versus males (58.4% vs. 41.6%; except for scoliosis: 48.9% vs. 51.1%), and in those with TSC2 versus TSC1 (67.0% vs. 21.1%; except for thyroid adenoma: 42.9% vs. 57.1%). In the 65 individuals with reported malignancies, the most common were renal cell carcinoma (47.7%), followed by breast (10.8%) and thyroid cancer (9.2%). Although malignancies were more common in adult patients, 26.1% were reported in children and 63.1% in individuals < 40 years. TSC1 mutations were over-represented in individuals with malignancies compared to the overall TOSCA cohort (32.1% vs. 18.5%). Conclusion Rare manifestations were observed in a significant proportion of individuals with TSC. We recommend further examination of rare manifestations in TSC. Collectively, malignancies were infrequent findings in our cohort. However, compared to the general population, malignant tumors occurred earlier in age and some tumor types were more common. DA - 2021-07-06 DB - OpenUCT DP - University of Cape Town IS - Article number: 301 J1 - Orphanet Journal of Rare Diseases KW - Rare manifestation KW - Malignancy KW - TOSCA KW - TSC KW - Tuberous sclerosis complex LK - https://open.uct.ac.za PY - 2021 T1 - Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA) TI - Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA) UR - http://hdl.handle.net/11427/35038 ER - en_ZA
dc.identifier.urihttps://doi.org/10.1186/s13023-021-01917-y
dc.identifier.urihttp://hdl.handle.net/11427/35038
dc.identifier.vancouvercitationSauter M, Belousova E, Benedik Mirjana P, Carter T, Cottin V, Curatolo P, et al. Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA). Orphanet Journal of Rare Diseases. 2021;16(Article number: 301) http://hdl.handle.net/11427/35038.en_ZA
dc.language.rfc3066en
dc.publisher.departmentDivision of Child and Adolescent Psychiatryen_US
dc.publisher.facultyFaculty of Health Sciencesen_US
dc.rights.holderThe Author(s)
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.sourceOrphanet Journal of Rare Diseasesen_US
dc.source.journalissueArticle number: 301en_US
dc.source.journalvolume16en_US
dc.source.urihttps://ojrd.biomedcentral.com/
dc.subjectRare manifestationen_US
dc.subjectMalignancyen_US
dc.subjectTOSCAen_US
dc.subjectTSCen_US
dc.subjectTuberous sclerosis complexen_US
dc.titleRare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA)en_US
dc.typeJournal Articleen_US
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