Rare manifestations and malignancies in tuberous sclerosis complex : findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA)
(2021) In Orphanet Journal of Rare Diseases 16. p.1-15- Abstract
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... (More)
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.
(Less)
- author
- contributor
- Rask, Olof LU
- author collaboration
- organization
- publishing date
- 2021-07-06
- type
- Contribution to journal
- publication status
- published
- subject
- keywords
- Adrenal Gland Neoplasms, Adult, Angiomyolipoma, Child, Female, Humans, Male, Mutation/genetics, Registries, Retrospective Studies, Tuberous Sclerosis/genetics, Tuberous Sclerosis Complex 1 Protein/genetics, Tuberous Sclerosis Complex 2 Protein/genetics
- in
- Orphanet Journal of Rare Diseases
- volume
- 16
- article number
- 301
- pages
- 1 - 15
- publisher
- BioMed Central (BMC)
- external identifiers
-
- scopus:85110984946
- pmid:34229737
- ISSN
- 1750-1172
- DOI
- 10.1186/s13023-021-01917-y
- language
- English
- LU publication?
- yes
- id
- b56a3692-5599-441d-8b21-dceaf851c300
- date added to LUP
- 2024-09-06 14:58:11
- date last changed
- 2025-01-25 19:16:31
@article{b56a3692-5599-441d-8b21-dceaf851c300,
abstract = {{<p>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.</p><p>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).</p><p>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%).</p><p>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.</p>}},
author = {{Sauter, Matthias and Belousova, Elena and Benedik, Mirjana P and Carter, Tom and Cottin, Vincent and Curatolo, Paolo and Dahlin, Maria and D'Amato, Lisa and d'Augères, Guillaume B and de Vries, Petrus J and Ferreira, José C and Feucht, Martha and Fladrowski, Carla and Hertzberg, Christoph and Jozwiak, Sergiusz and Lawson, John A and Macaya, Alfons and Marques, Ruben and Nabbout, Rima and O'Callaghan, Finbar and Qin, Jiong and Sander, Valentin and Shah, Seema and Takahashi, Yukitoshi and Touraine, Renaud and Youroukos, Sotiris and Zonnenberg, Bernard and Jansen, Anna and Kingswood, J Chris}},
issn = {{1750-1172}},
keywords = {{Adrenal Gland Neoplasms; Adult; Angiomyolipoma; Child; Female; Humans; Male; Mutation/genetics; Registries; Retrospective Studies; Tuberous Sclerosis/genetics; Tuberous Sclerosis Complex 1 Protein/genetics; Tuberous Sclerosis Complex 2 Protein/genetics}},
language = {{eng}},
month = {{07}},
pages = {{1--15}},
publisher = {{BioMed Central (BMC)}},
series = {{Orphanet Journal of Rare Diseases}},
title = {{Rare manifestations and malignancies in tuberous sclerosis complex : findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA)}},
url = {{http://dx.doi.org/10.1186/s13023-021-01917-y}},
doi = {{10.1186/s13023-021-01917-y}},
volume = {{16}},
year = {{2021}},
}