2026-04-17T01:54:37Zhttps://recercat.cat/oai/request

oai:recercat.cat:11351/70882025-11-08T13:42:49Zcom_2072_378070com_2072_378040col_2072_378092

urn:hdl:11351/7088 Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA) Sauter, Matthias Belousova, Elena Perkovic Benedik, Mirjana Carter, Tom Cottin, Vincent Curatolo, Paolo Macaya Ruíz, Alfons Esclerosi tuberosa - Aspectes genètics Registres mèdics Malalties rares DISEASES::Neoplasms::Hamartoma::Tuberous Sclerosis Other subheadings::Other subheadings::Other subheadings::/genetics ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT::Investigative Techniques::Epidemiologic Methods::Data Collection::Registries DISEASES::Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Rare Diseases ENFERMEDADES::neoplasias::hamartoma::esclerosis tuberosa Otros calificadores::Otros calificadores::Otros calificadores::/genética TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS::técnicas de investigación::métodos epidemiológicos::recopilación de datos::registros ENFERMEDADES::afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::enfermedades raras Manifestación rara; Tosca; Complejo de esclerosis tuberosa Manifestació rara; Tosca; Complex d'esclerosi tuberosa Rare manifestation; Tosca; Tuberous sclerosis complex 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. The study was funded by Novartis Pharma AG. Novartis has contributed to the study design, data analysis, and the decision to publish. Novartis authors reviewed the draft for submission. 2022-02-25T13:32:54Z 2022-02-25T13:32:54Z 2021-07-06 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Orphanet Journal of Rare Diseases;16 https://doi.org/10.1186/s13023-021-01917-y Attribution 4.0 International http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess BMC Scientia