1. Rare manifestations and malignancies in tuberous sclerosis complex: Findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA)
- Author
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Sauter, Matthias, Belousova, Elena, Benedik, Mirjana P., Carter, Tom, Cottin, Vincent, Curatolo, Paolo, Dahlin, Maria, D'Amato, Lisa, D'Augeres, Guillaume B., de Vries, Petrus J., Ferreira, Jose 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, Verhelst, Helene, on behalf of the TOSCA investigators, [ missing ], Institut Català de la Salut, [Sauter M] Klinikum Kempten, Klinikverbund Allgäu, Robert-Weixler-Str. 50, 87439 Kempten, Germany. [Belousova E] Research and Clinical Institute of Pediatrics, Pirogov Russian National Research Medical University, Moscow, Russian Federation. [Benedik MP] SPS Pediatrična Klinika, Ljubljana, Slovenia. [Carter T] TSA Tuberous Sclerosis Association, Nottingham, UK. [Cottin V] Hôpital Louis Pradel, Claude Bernard University Lyon 1, Lyon, France. [Curatolo P] Tor Vergata University Hospital, Rome, Italy. [Macaya A] Vall d’Hebron Hospital Universitari, Barcelona, Spain, Vall d'Hebron Barcelona Hospital Campus, Division of Child and Adolescent Psychiatry, Faculty of Health Sciences, Public Health Sciences, Mental Health and Wellbeing research group, Neurogenetics, Neuroprotection & Neuromodulation, and Pediatrics
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0301 basic medicine ,Male ,Angiomyolipoma ,Adrenal Gland Neoplasms ,RECOMMENDATIONS ,Tuberous Sclerosis Complex 1 Protein ,técnicas de investigación::métodos epidemiológicos::recopilación de datos::registros [TÉCNICAS Y EQUIPOS ANALÍTICOS, DIAGNÓSTICOS Y TERAPÉUTICOS] ,Esclerosi tuberosa - Aspectes genètics ,Tuberous sclerosis ,0302 clinical medicine ,afecciones patológicas, signos y síntomas::procesos patológicos::atributos de la enfermedad::enfermedades raras [ENFERMEDADES] ,TUMOR ,neoplasias::hamartoma::esclerosis tuberosa [ENFERMEDADES] ,Tuberous Sclerosis ,Medicine and Health Sciences ,Pharmacology (medical) ,Registries ,Child ,Thyroid cancer ,Genetics (clinical) ,TSC ,education.field_of_study ,Otros calificadores::Otros calificadores::/genética [Otros calificadores] ,General Medicine ,Registres mèdics ,medicine.anatomical_structure ,Tuberous Sclerosis/genetics ,Medicine ,Female ,Malalties rares ,Adult ,medicine.medical_specialty ,congenital, hereditary, and neonatal diseases and abnormalities ,Tuberous Sclerosis Complex 1 Protein/genetics ,LYMPHEDEMA ,Mutation/genetics ,Rare manifestation ,Population ,03 medical and health sciences ,Tuberous Sclerosis Complex 2 Protein ,medicine ,Other subheadings::Other subheadings::/genetics [Other subheadings] ,Humans ,Pediatrics, Perinatology, and Child Health ,education ,Hemihypertrophy ,TOSCA ,Retrospective Studies ,business.industry ,Pathological Conditions, Signs and Symptoms::Pathologic Processes::Disease Attributes::Rare Diseases [DISEASES] ,Research ,Thyroid adenoma ,Malignancy ,medicine.disease ,Dermatology ,Investigative Techniques::Epidemiologic Methods::Data Collection::Registries [ANALYTICAL, DIAGNOSTIC AND THERAPEUTIC TECHNIQUES, AND EQUIPMENT] ,030104 developmental biology ,Tuberous Sclerosis Complex 2 Protein/genetics ,Tuberous sclerosis complex ,Mutation ,TSC1 ,business ,030217 neurology & neurosurgery ,Rare disease ,Neoplasms::Hamartoma::Tuberous Sclerosis [DISEASES] - Abstract
BackgroundTuberous sclerosis complex (TSC) is a rare multisystem autosomal dominant disorder caused by pathogenic variants in either theTSC1orTSC2gene. 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.MethodsTuberOus 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 (TSC1orTSC2).ResultsOverall, 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 withTSC2versusTSC1(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 TSC1mutations were over-represented in individuals with malignancies compared to the overall TOSCA cohort (32.1% vs. 18.5%).ConclusionRare 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.
- Published
- 2021