Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA)
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 work...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMC
2021-07-01
|
| Series: | Orphanet Journal of Rare Diseases |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13023-021-01917-y |
| _version_ | 1819156730973519872 |
|---|---|
| author | Matthias Sauter Elena Belousova Mirjana P. Benedik Tom Carter Vincent Cottin Paolo Curatolo Maria Dahlin Lisa D’Amato Guillaume B. d’Augères Petrus J. de Vries José C. Ferreira Martha Feucht Carla Fladrowski Christoph Hertzberg Sergiusz Jozwiak John A. Lawson Alfons Macaya Ruben Marques Rima Nabbout Finbar O’Callaghan Jiong Qin Valentin Sander Seema Shah Yukitoshi Takahashi Renaud Touraine Sotiris Youroukos Bernard Zonnenberg Anna Jansen J. Chris Kingswood the TOSCA investigators |
| author_facet | Matthias Sauter Elena Belousova Mirjana P. Benedik Tom Carter Vincent Cottin Paolo Curatolo Maria Dahlin Lisa D’Amato Guillaume B. d’Augères Petrus J. de Vries José C. Ferreira Martha Feucht Carla Fladrowski Christoph Hertzberg Sergiusz Jozwiak John A. Lawson Alfons Macaya Ruben Marques Rima Nabbout Finbar O’Callaghan Jiong Qin Valentin Sander Seema Shah Yukitoshi Takahashi Renaud Touraine Sotiris Youroukos Bernard Zonnenberg Anna Jansen J. Chris Kingswood the TOSCA investigators |
| author_sort | Matthias Sauter |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-22T15:57:31Z |
| format | Article |
| id | doaj.art-3dc0f80054b74f879b4183fb55c67671 |
| institution | Directory Open Access Journal |
| issn | 1750-1172 |
| language | English |
| last_indexed | 2024-12-22T15:57:31Z |
| publishDate | 2021-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Orphanet Journal of Rare Diseases |
| spelling | doaj.art-3dc0f80054b74f879b4183fb55c676712022-12-21T18:20:44ZengBMCOrphanet Journal of Rare Diseases1750-11722021-07-0116111510.1186/s13023-021-01917-yRare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA)Matthias Sauter0Elena Belousova1Mirjana P. Benedik2Tom Carter3Vincent Cottin4Paolo Curatolo5Maria Dahlin6Lisa D’Amato7Guillaume B. d’Augères8Petrus J. de Vries9José C. Ferreira10Martha Feucht11Carla Fladrowski12Christoph Hertzberg13Sergiusz Jozwiak14John A. Lawson15Alfons Macaya16Ruben Marques17Rima Nabbout18Finbar O’Callaghan19Jiong Qin20Valentin Sander21Seema Shah22Yukitoshi Takahashi23Renaud Touraine24Sotiris Youroukos25Bernard Zonnenberg26Anna Jansen27J. Chris Kingswood28the TOSCA investigatorsKlinikum KemptenResearch and Clinical Institute of Pediatrics, Pirogov Russian National Research Medical UniversitySPS Pediatrična KlinikaTSA Tuberous Sclerosis AssociationHôpital Louis PradelTor Vergata University HospitalKarolinska University HospitalNovartis Farma S.P.AAssociation Sclérose Tubéreuse de BournevilleDivision of Child and Adolescent Psychiatry, University of Cape TownCentro Hospitalar Lisboa OcidentalUniversitätsklinik Für Kinder-Und Jugendheilkunde (Affiliated Partner of the ERN EpiCARE)Associazione Sclerosi Tuberosa ONLUSVivantes-Klinikum NeuköllnDepartment of Child Neurology, Medical University of WarsawThe Tuberous Sclerosis Multidisciplinary Management Clinic, Sydney Children’s HospitalHospital Universitari Vall D’HebronNovartis Farma S.P.ADepartment of Pediatric Neurology, Necker Enfants Malades Hospital, Imagine Institute, Paris Descartes UniversityInstitute of Child Health, University College LondonDepartment of Pediatrics, Peking University People’s HospitalTallinn Children HospitalNovartis Healthcare Pvt. LtdNational Epilepsy Center, Shizuoka Institute of Epilepsy and Neurological DisordersDepartment of Genetics, CHU-Hôpital NordSt. Sophia Children’s HospitalUniversity Medical CenterPediatric Neurology Unit, Department of Pediatrics, UZ Brussel VUBCardiology Clinical Academic Group, Molecular and Clinical Sciences Research Centre, St Georges University of LondonAbstract 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.https://doi.org/10.1186/s13023-021-01917-yRare manifestationMalignancyTOSCATSCTuberous sclerosis complex |
| spellingShingle | Matthias Sauter Elena Belousova Mirjana P. Benedik Tom Carter Vincent Cottin Paolo Curatolo Maria Dahlin Lisa D’Amato Guillaume B. d’Augères Petrus J. de Vries José C. Ferreira Martha Feucht Carla Fladrowski Christoph Hertzberg Sergiusz Jozwiak John A. Lawson Alfons Macaya Ruben Marques Rima Nabbout Finbar O’Callaghan Jiong Qin Valentin Sander Seema Shah Yukitoshi Takahashi Renaud Touraine Sotiris Youroukos Bernard Zonnenberg Anna Jansen J. Chris Kingswood the TOSCA investigators Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA) Orphanet Journal of Rare Diseases Rare manifestation Malignancy TOSCA TSC Tuberous sclerosis complex |
| title | Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA) |
| title_full | Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA) |
| title_fullStr | Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA) |
| title_full_unstemmed | Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA) |
| title_short | Rare manifestations and malignancies in tuberous sclerosis complex: findings from the TuberOus SClerosis registry to increAse disease awareness (TOSCA) |
| title_sort | rare manifestations and malignancies in tuberous sclerosis complex findings from the tuberous sclerosis registry to increase disease awareness tosca |
| topic | Rare manifestation Malignancy TOSCA TSC Tuberous sclerosis complex |
| url | https://doi.org/10.1186/s13023-021-01917-y |
| work_keys_str_mv | AT matthiassauter raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT elenabelousova raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT mirjanapbenedik raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT tomcarter raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT vincentcottin raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT paolocuratolo raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT mariadahlin raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT lisadamato raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT guillaumebdaugeres raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT petrusjdevries raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT josecferreira raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT marthafeucht raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT carlafladrowski raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT christophhertzberg raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT sergiuszjozwiak raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT johnalawson raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT alfonsmacaya raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT rubenmarques raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT rimanabbout raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT finbarocallaghan raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT jiongqin raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT valentinsander raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT seemashah raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT yukitoshitakahashi raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT renaudtouraine raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT sotirisyouroukos raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT bernardzonnenberg raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT annajansen raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT jchriskingswood raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca AT thetoscainvestigators raremanifestationsandmalignanciesintuberoussclerosiscomplexfindingsfromthetuberoussclerosisregistrytoincreasediseaseawarenesstosca |