Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA)
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Published:2021-07-06
Issue:1
Volume:16
Page:
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ISSN:1750-1172
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Container-title:Orphanet Journal of Rare Diseases
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language:en
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Short-container-title:Orphanet J Rare Dis
Author:
Sauter MatthiasORCID, Belousova Elena, Benedik Mirjana P., Carter Tom, Cottin Vincent, Curatolo Paolo, Dahlin Maria, D’Amato Lisa, d’Augères Guillaume B., de Vries Petrus J., Ferreira José C., Feucht Martha, Fladrowski Carla, Hertzberg Christoph, Jozwiak Sergiusz, Lawson John A., Macaya Alfons, Marques Ruben, Nabbout Rima, O’Callaghan Finbar, Qin Jiong, Sander Valentin, Shah Seema, Takahashi Yukitoshi, Touraine Renaud, Youroukos Sotiris, Zonnenberg Bernard, Jansen Anna, Kingswood J. Chris, Shinohara Nobuo, Horie Shigeo, Kubota Masaya, Tohyama Jun, Imai Katsumi, Kaneda Mari, Kaneko Hideo, Uchida Yasushi, Kirino Tomoko, Endo Shoichi, Inoue Yoshikazu, Uruno Katsuhisa, Serdaroglu Ayse, Yapici Zuhal, Anlar Banu, Altunbasak Sakir, Lvova Olga, Belyaev Oleg Valeryevich, Agranovich Oleg, Levitina Elena Vladislavovna, Maksimova Yulia Vladimirovna, Karas Antonina, Jiang Yuwu, Zou Liping, Xu Kaifeng, Zhang Yushi, Luan Guoming, Zhang Yuqin, Wang Yi, Jin Meiling, Ye Dingwei, Liao Weiping, Zhou Liemin, Liu Jie, Liao Jianxiang, YAN Bo, Deng Yanchun, Jiang Li, Liu Zhisheng, Huang Shaoping, Li Hua, Kim Kijoong, Chen Pei-Lung, Lee Hsiu-Fen, Tsai Jeng-Dau, Chi Ching-Shiang, Huang Chao-Ching, Riney Kate, Yates Deborah, Kwan Patrick, Likasitwattanakul Surachai, Nabangchang Charcrin, Chomtho Lunliya Thampratankul Krisnachai, Katanyuwong Kamornwan, Sriudomkajorn Somjit, Wilmshurst Jo, Segel Reeval, Gilboa Tal, Tzadok Michal, Valevski Aviva Fattal-, Papathanasopoulos Panagiotis, Papavasiliou Antigone Syrigou, Giannakodimos Stylianos, Gatzonis Stylianos, Pavlou Evangelos, Tzoufi Meropi, Vergeer A. M. H., Dhooghe Marc, Verhelst Hélène, Roelens Filip, Nassogne Marie Cecile, Defresne Pierre, De Waele Liesbeth, Leroy Patricia, Demonceau Nathalie, Legros Benjamin, Van Bogaert Patrick, Ceulemans Berten, Dom Lina, Castelnau Pierre, De Saint Martin Anne, Riquet Audrey, Milh Mathieu, Cances Claude, Pedespan Jean-Michel, Ville Dorothee, Roubertie Agathe, Auvin Stéphane, Berquin Patrick, Richelme Christian, Allaire Catherine, Gueden Sophie, Tich Sylvie Nguyen The, Godet Bertrand, Rojas Maria Luz Ruiz Falco, Planas Jaume Campistol, Bermejo Antonio Martinez, Dura Patricia Smeyers, Aparicio Susana Roldan, Gonzalez Maria Jesus Martinez, Pison Javier Lopez, Barca Manuel Oscar Blanco, Laso Eduardo Lopez, Luengo Olga Alonso, Rodriguez Francisco Javier Aguirre, Dieguez Ignacio Malaga, Salas Ana Camacho, Carrera Itxaso Marti, Salcedo Eduardo Martinez, Petri Maria Eugenia Yoldi, Candela Ramon Cancho, da Conceicao Carrilho Ines, Vieira Jose Pedro, da Silva Oliveira Monteiro José Paulo, de Oliveira Ferreira Leao Miguel Jorge Santos, Luis Catarina Sofia Marceano Ribeiro, Mendonca Carla Pires, Endziniene Milda, Strautmanis Jurgis, Talvik Inga, Canevini Maria Paola, Gambardella Antonio, Pruna Dario, Buono Salvatore, Fontana Elena, Bernardina Bernardo Dalla, Burloiu Carmen, Cosma Iuliu Stefan Bacos, Vintan Mihaela Adela, Popescu Laura, Zitterbart Karel, Payerova Jaroslava, Bratsky Ladislav, Zilinska Zuzana, Gruber-Sedlmayr Ursula, Baumann Matthias, Haberlandt Edda, Rostasy Kevin, Pataraia Ekaterina, Elmslie Frances, Johnston Clare Ann, Crawford Pamela, Uldall Peter, Uvebrant Paul, Rask Olof, Bjoernvold Marit, Brodtkorb Eylert, Sloerdahl Andreas, Solhoff Ragnar, Jaatun Martine Sofie Gilje, Mandera Marek, Radzikowska Elzbieta Janina, Wysocki Mariusz, Fischereder Michael, Kurlemann Gerhard, Wilken Bernd, Wiemer-Kruel Adelheid, Budde Klemens, Marquard Klaus, Knuf Markus, Hahn Andreas, Hartmann Hans, Merkenschlager Andreas, Trollmann Regina,
Abstract
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 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.
Funder
Novartis Pharma AG
Publisher
Springer Science and Business Media LLC
Subject
Pharmacology (medical),Genetics (clinical),General Medicine
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