TuberOus SClerosis registry to increase disease Awareness (TOSCA) – baseline data on 2093 patients

Orphanet Journal of Rare Diseases - Tập 12 - Trang 1-13 - 2017
John C. Kingswood1, Guillaume B. d’Augères2, Elena Belousova3, José C. Ferreira4, Tom Carter5, Ramon Castellana6, Vincent Cottin7, Paolo Curatolo8, Maria Dahlin9, Petrus J. de Vries10, Martha Feucht11, Carla Fladrowski12,13, Gabriella Gislimberti14, Christoph Hertzberg15, Sergiusz Jozwiak16, John A. Lawson17, Alfons Macaya18, Rima Nabbout19, Finbar O’Callaghan20, Mirjana P. Benedik21, Jiong Qin22, Ruben Marques14, Valentin Sander23, Matthias Sauter24, Yukitoshi Takahashi25, Renaud Touraine26, Sotiris Youroukos27, Bernard Zonnenberg28, Anna C. Jansen29
1Sussex Kidney Unit, Royal Sussex County Hospital, Brighton, UK
2Association Sclérose Tubéreuse de Bourneville, Gradignan, France
3Moscow Institute of Pediatrics and Pediatric Surgery, Moscow, Russian Federation
4Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal
5TSA Tuberous Sclerosis Association, Nottingham, UK
6Novartis Farmacéutica SA, Gran Vía Corts Catalanes, Barcelona, Spain
7Hôpital Louis Pradel, Claude Bernard University Lyon 1, Lyon, France
8Tor Vergata University Hospital, Rome, Italy
9Karolinska University Hospital, Stockholm, Sweden
10Division of Child and Adolescent Psychiatry, University of Cape Town, Cape Town, South Africa
11Universitätsklinik für Kinder-und Jugendheilkunde, Vienna, Austria
12Associazione Sclerosi Tuberosa ONLUS, Milan, Italy
13European Tuberous Sclerosis Complex Association, In den Birken, Dattein, Germany
14Novartis Farma S.p.A, Origgio, Italy
15Vivantes-Klinikum Neukölln, Berlin, Germany
16Department of Child Neurology, Warsaw Medical University, Warsaw, Poland
17The Tuberous Sclerosis Multidisciplinary Management Clinic, Sydney Children’s Hospital, Randwick, Australia
18Hospital Universitari Vall d’Hebron, Barcelona, Spain
19Department of Pediatric Neurology, Necker Enfants Malades Hospital, Paris Descartes University, Paris, France
20Institute of Child Health, University College London, London, UK
21SPS Pediatrična Klinika, Ljubljana, Slovenia
22Department of Pediatrics, Peking University People’s Hospital (PKUPH), Beijing, China
23Tallinn Children Hospital, Tallinn, Estonia
24Klinikverbund Kempten-Oberallgäu gGmbH, Kempten, Germany
25National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, Shizuoka, Japan
26Hôpital Nord, Saint Etienne, France
27“St. Sophia” Children’s Hospital, Athens, Greece
28University Medical Center Utrecht, Netherlands
29UZ Brussel VUB, Brussels, Belgium

Tóm tắt

Tuberous sclerosis complex (TSC) is a rare autosomal dominant genetic disorder. Many gaps remain in the understanding of TSC because of the complexity in clinical presentation. The TuberOus SClerosis registry to increase disease Awareness (TOSCA) is an international disease registry designed to address knowledge gaps in the natural history and management of TSC. Here, we present the baseline data of TOSCA cohort. Patients of any age diagnosed with TSC, having a documented visit for TSC within the preceding 12 months, or newly diagnosed individuals were included. The registry includes a “core” section designed to record detailed background information on each patient including disease manifestations, interventions, and outcomes collected at baseline and updated annually. “Subsections” of the registry recorded additional data related to specific features of TSC. Baseline “core” data from 2093 patients enrolled from 170 sites across 31 countries were available at the cut-off date September 30, 2014. Median age of patients at enrollment was 13 years (range, 0–71) and at diagnosis of TSC was 1 year (range, 0–69). The occurrence rates of major manifestations of TSC included – cortical tubers (82.2%), subependymal nodules (78.2%), subependymal giant cell astrocytomas (24.4%), renal angiomyolipomas (47.2%), lymphangioleiomyomatosis (6.9%), cardiac rhabdomyomas (34.3%), facial angiofibromas (57.3%), forehead plaque (14.1%), ≥ 3 hypomelanotic macules (66.8%), and shagreen patches (27.4%). Epilepsy was reported in 1748 (83.5%) patients, of which 1372 were diagnosed at ≤ 2 years (78%). Intellectual disability was identified in 451 (54.9%) patients of those assessed. TSC-associated neuropsychiatric disorders (TAND) were diagnosed late, and not evaluated in 30–50% of patients. TOSCA is the largest clinical case series of TSC to date. It provided a detailed description of the disease trajectory with increased awareness of various TSC manifestations. The rates of different features of TSC reported here reflect the age range and referral patterns of clinics contributing patients to the cohort. Documentation of TAND and LAM was poor. A widespread adoption of the international TSC assessment and treatment guidelines, including use of the TAND Checklist, could improve surveillance. The registry provides valuable insights into the necessity for monitoring, timing, and indications for the treatment of TSC.

Tài liệu tham khảo

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Orphanet Journal of Rare Diseases

Tập 12

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