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

作者：Matthias Sauter, Elena Belousova, Mirjana P. Benedik, Tom Carter, Vincent Cottin, Paolo Curatolo, Maria Dahlin, Lisa D’Amato, Guillaume Beaure d’Augères, Petrus J. de Vries, José C. Ferreira, Martha Feucht, Carla Fladrowski, Christoph Hertzberg, Sergiusz Jóźwiak, John A. Lawson, Alfons Macaya, Rubén Marques, Rima Nabbout, Finbar O’Callaghan, Jiong Qin, Valentin Sander, Seema Shah, Yukitoshi Takahashi, Renaud Touraine, Sotiris Youroukos, Bernard A. Zonnenberg, Anna Jansen, J.C. Kingswood, the TOSCA investigators, Nobuo Shinohara, Shigeo Horie, Masaya Kubota, Jun Tohyama, Katsumi Imai, Mari Kaneda, Hideo Kaneko, Yasushi Uchida, Tomoko Kirino, Shoichi Endo, Yoshikazu Inoue, Katsuhisa Uruno, Ayşe Serdaroğlu, Zühal Yapıcı, Banu Anlar, Şakìr Altunbaşak, O. Lvova, O. V. Belyaev, Oleg Agranovich, Е. В. Левитина, Yu. V. Maksimova, Antonina Karas, Yuwu Jiang, Liping Zou, Kai‐Feng Xu, Yushi Zhang, Guoming Luan, Yuqin Zhang, Yi Wang, Meiling Jin, Dingwei Ye, Weiping Liao, Liemin Zhou, Jie Liu, Jianxiang Liao, Bo Yan, Yanchun Deng, Li Jiang, Zhisheng Liu, Shaoping Huang, Hua Li, Kijoong Kim, Pei‐Lung Chen, Hsiu-Fen Lee, Jeng‐Dau Tsai, Ching‐Shiang Chi, Chao Huang, Kate Riney, Deborah Yates, Patrick Kwan, Surachai Likasitwattanakul, Charcrin Nabangchang, Lunliya Thampratankul Krisnachai Chomtho, Kamornwan Katanyuwong, Somjit Sri-udomkajorn, Jo M. Wilmshurst, Reeval Segel, Tal Gilboa, Michal Tzadok, Aviva Fattal- Valevski, Panagiotis Papathanasopoulos, Antigone Papavasiliou, Stylianos Giannakodimos, Stylianos Gatzonis, Evangelos Pavlou, Meropi Tzoufi, A. M. H. Vergeer, Marc D’Hooghe, Hélène Verhelst, Filip Roelens, Marie‐Cécile Nassogne, Pierre Defresne, Liesbeth De Waele, Patricia Leroy, Nathalie Demonceau, Benjamin Legros, Patrick Van Bogaert, Berten Ceulemans, Lina Dom, Pierre Castelnau, Anne de Saint Martin, Audrey Riquet, Mathieu Milh, Claude Cancés, Jean‐Michel Pedespan, Dorothée Ville, Agathe Roubertie, Stéphane Auvin, Patrick Berquin, Christian Richelme, Catherine Allaire, Sophie Guéden, Sylvie Nguyen The Tich, Bertrand Godet, Maria Luz Ruiz Falco Rojas, Jaume Planas, Antonio Martínez Bermejo, Patricia Smeyers Durá, Susana Roldan Aparicio, M. J. Martínez González, Javier López Pisón, Manuel Oscar Blanco Barca, Eduardo Laso, Olga Alonso Luengo, Francisco Javier Aguirre Rodriguez, Ignacio Malaga Dieguez, Ana Camacho Salas, Itxaso Marti Carrera, Eduardo Martínez Salcedo, Maria Eugenia Yoldi Petri, Ramón Cancho Candela, Ines da Conceicao Carrilho, José Pedro Vieira, José Paulo da Silva Oliveira Monteiro, Miguel Jorge Santos de Oliveira Ferreira Leao, Catarina Sofia Marceano Ribeiro Luis, Carla Pires Mendonca, Milda Endzinienė, Jurģis Strautmanis, Inga Talvik, Maria Paola Canevini, Antonio Gambardella, Dario Pruna, Salvatore Buono, Elena Fontana, Bernardo Dalla Bernardina, Carmen Burloiu, Iuliu Stefan Bacos Cosma, Mihaela Adela Vințan, Laura Popescu, Karel Zitterbart, Jaroslava Payerova, Ladislav Bratsky, Zuzana Žilinská, U Gruber‐Sedlmayr, Matthias Baumann, Edda Haberlandt, Kevin Rostásy, Ekaterina Pataraia, Frances Elmslie, Clare Johnston, Pamela Crawford, Peter Uldall, Paul Uvebrant, Olof Rask, Marit Bjoernvold, Eylert Brodtkorb, Andreas Sloerdahl, Ragnar Solhoff, Martine Sofie Gilje Jaatun, Marek Mandera, Elzbieta Janina Radzikowska, Mariusz Wysocki, Michael Fischereder, Gerhard Kurlemann, Bernd Wilken, Adelheid Wiemer‐Kruel, Klemens Budde, Klaus Marquard, Markus Knuf, Andreas Hahn, Hans Hartmann, Andreas Merkenschlager, Regina Trollmann · 发表于：Orphanet Journal of Rare Diseases · 年份：2021 · DOI：10.1186/s13023-021-01917-y · 被引用次数：45 · 研究领域：Tuberous Sclerosis Complex Research、Parasitic infections in humans and animals、Vascular Tumors and Angiosarcomas

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%), ...