title: TuberOus SClerosis registry to increase disease Awareness (TOSCA) - baseline data on 2093 patients.
abstract: 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.
authors.affiliation: Sussex Kidney Unit, Royal Sussex County Hospital, Eastern Road, Brighton, BN2 5BE, UK. chris.kingswood@bsuh.nhs.uk.
authors.forename: John C
authors.initials: JC
authors.lastname: Kingswood
authors.affiliation: Association Sclérose Tubéreuse de Bourneville, Gradignan, France.
authors.forename: Guillaume B
authors.initials: GB
authors.lastname: d'Augères
authors.affiliation: Moscow Institute of Pediatrics and Pediatric Surgery, Moscow, Russian Federation.
authors.forename: Elena
authors.initials: E
authors.lastname: Belousova
authors.affiliation: Centro Hospitalar Lisboa Ocidental, Lisbon, Portugal.
authors.forename: José C
authors.initials: JC
authors.lastname: Ferreira
authors.affiliation: TSA Tuberous Sclerosis Association, Nottingham, UK.
authors.forename: Tom
authors.initials: T
authors.lastname: Carter
authors.affiliation: Novartis Farmacéutica SA, Gran Vía Corts Catalanes, Barcelona, Spain.
authors.forename: Ramon
authors.initials: R
authors.lastname: Castellana
authors.affiliation: Hôpital Louis Pradel, Claude Bernard University Lyon 1, Lyon, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Cottin
authors.affiliation: Tor Vergata University Hospital, Rome, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Curatolo
authors.affiliation: Karolinska University Hospital, Stockholm, Sweden.
authors.forename: Maria
authors.initials: M
authors.lastname: Dahlin
authors.affiliation: Division of Child and Adolescent Psychiatry, University of Cape Town, Cape Town, South Africa.
authors.forename: Petrus J
authors.initials: PJ
authors.lastname: de Vries
authors.affiliation: Universitätsklinik für Kinder-und Jugendheilkunde, Vienna, Austria.
authors.forename: Martha
authors.initials: M
authors.lastname: Feucht
authors.affiliation: Associazione Sclerosi Tuberosa ONLUS, Milan, Italy.|European Tuberous Sclerosis Complex Association, In den Birken, Dattein, Germany.
authors.forename: Carla
authors.initials: C
authors.lastname: Fladrowski
authors.affiliation: Novartis Farma S.p.A, Origgio, Italy.
authors.forename: Gabriella
authors.initials: G
authors.lastname: Gislimberti
authors.affiliation: Vivantes-Klinikum Neukölln, Berlin, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Hertzberg
authors.affiliation: Department of Child Neurology, Warsaw Medical University, Warsaw, Poland.
authors.forename: Sergiusz
authors.initials: S
authors.lastname: Jozwiak
authors.affiliation: The Tuberous Sclerosis Multidisciplinary Management Clinic, Sydney Children's Hospital, Randwick, NSW, Australia.
authors.forename: John A
authors.initials: JA
authors.lastname: Lawson
authors.affiliation: Hospital Universitari Vall d'Hebron, Barcelona, Spain.
authors.forename: Alfons
authors.initials: A
authors.lastname: Macaya
authors.affiliation: Department of pediatric neurology, Necker Enfants Malades Hospital, Paris Descartes University, Paris, France.
authors.forename: Rima
authors.initials: R
authors.lastname: Nabbout
authors.affiliation: Institute of Child Health, University College London, London, UK.
authors.forename: Finbar
authors.initials: F
authors.lastname: O'Callaghan
authors.affiliation: SPS Pediatrična Klinika, Ljubljana, Slovenia.
authors.forename: Mirjana P
authors.initials: MP
authors.lastname: Benedik
authors.affiliation: Department of Pediatrics, Peking University People's Hospital (PKUPH), Beijing, China.
authors.forename: Jiong
authors.initials: J
authors.lastname: Qin
authors.affiliation: Novartis Farma S.p.A, Origgio, Italy.
authors.forename: Ruben
authors.initials: R
authors.lastname: Marques
authors.affiliation: Tallinn Children Hospital, Tallinn, Estonia.
authors.forename: Valentin
authors.initials: V
authors.lastname: Sander
authors.affiliation: Klinikverbund Kempten-Oberallgäu gGmbH, Kempten, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Sauter
authors.affiliation: National Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological Disorders, NHO, 886 Urushiyama Aoi-ku, Shizuoka, Japan.
authors.forename: Yukitoshi
authors.initials: Y
authors.lastname: Takahashi
authors.affiliation: Hôpital Nord, Saint Etienne, France.
authors.forename: Renaud
authors.initials: R
authors.lastname: Touraine
authors.affiliation: "St. Sophia" Children's Hospital, Athens, Greece.
authors.forename: Sotiris
authors.initials: S
authors.lastname: Youroukos
authors.affiliation: University Medical Center, Utrecht, Netherlands.
authors.forename: Bernard
authors.initials: B
authors.lastname: Zonnenberg
authors.affiliation: UZ Brussel VUB, Brussels, Belgium.
authors.forename: Anna C
authors.initials: AC
authors.lastname: Jansen
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D018207:Angiomyolipoma / Q000453:epidemiology; D001364:Awareness; D002648:Child; D002675:Child, Preschool; D004827:Epilepsy / Q000453:epidemiology; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D018192:Lymphangioleiomyomatosis / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D012042:Registries; D014402:Tuberous Sclerosis / Q000453:epidemiology*; D055815:Young Adult
keywords: Angiomyolipoma; Epilepsy; Registry; Subependymal giant cell astrocytoma; TOSCA; Tuberous sclerosis