Natural clusters of tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND): new findings from the TOSCA TAND research project.

De Vries PJ, Belousova E, Benedik MP, Carter T, Cottin V, Curatolo P, D'Amato L, Beure D'Augeres G, Ferreira JC, Feucht M, Fladrowski C, Hertzberg C, Jozwiak S, Lawson JA, Macaya A, Marques R, Nabbout R, O'Callaghan F, Qin J, Sander V, Sauter M, Shah S, Takahashi Y, Touraine R, Youroukos S, Zonnenberg B, Kingswood JC, Jansen AC (2020)

Publication Type: Journal article

Publication year: 2020


Book Volume: 12

Journal Issue: 1

DOI: 10.1186/s11689-020-09327-0


BACKGROUND: Tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND) have unique, individual patterns that pose significant challenges for diagnosis, psycho-education, and intervention planning. A recent study suggested that it may be feasible to use TAND Checklist data and data-driven methods to generate natural TAND clusters. However, the study had a small sample size and data from only two countries. Here, we investigated the replicability of identifying natural TAND clusters from a larger and more diverse sample from the TOSCA study. METHODS: As part of the TOSCA international TSC registry study, this embedded research project collected TAND Checklist data from individuals with TSC. Correlation coefficients were calculated for TAND variables to generate a correlation matrix. Hierarchical cluster and factor analysis methods were used for data reduction and identification of natural TAND clusters. RESULTS: A total of 85 individuals with TSC (female:male, 40:45) from 7 countries were enrolled. Cluster analysis grouped the TAND variables into 6 clusters: a scholastic cluster (reading, writing, spelling, mathematics, visuo-spatial difficulties, disorientation), a hyperactive/impulsive cluster (hyperactivity, impulsivity, self-injurious behavior), a mood/anxiety cluster (anxiety, depressed mood, sleep difficulties, shyness), a neuropsychological cluster (attention/concentration difficulties, memory, attention, dual/multi-tasking, executive skills deficits), a dysregulated behavior cluster (mood swings, aggressive outbursts, temper tantrums), and an autism spectrum disorder (ASD)-like cluster (delayed language, poor eye contact, repetitive behaviors, unusual use of language, inflexibility, difficulties associated with eating). The natural clusters mapped reasonably well onto the six-factor solution generated. Comparison between cluster and factor solutions from this study and the earlier feasibility study showed significant similarity, particularly in cluster solutions. CONCLUSIONS: Results from this TOSCA research project in an independent international data set showed that the combination of cluster analysis and factor analysis may be able to identify clinically meaningful natural TAND clusters. Findings were remarkably similar to those identified in the earlier feasibility study, supporting the potential robustness of these natural TAND clusters. Further steps should include examination of larger samples, investigation of internal consistency, and evaluation of the robustness of the proposed natural clusters.

Involved external institutions

Pirogov Russian National Research Medical University (RSMU / RNRMU) RU Russian Federation (RU) Ljubljana University Medical Centre (Ljubljana UMC) / Univerzitetni klinični center Ljubljana SI Slovenia (SI) Tuberous Sclerosis Association (TSA) GB United Kingdom (GB) Université Claude Bernard Lyon 1 (UCB) FR France (FR) Policlinico Tor Vergata IT Italy (IT) Association Sclérose Tubéreuse de Bourneville (ASTB) FR France (FR) Medizinische Universität Wien AT Austria (AT) Tuberous Sclerosis Association - APS (AST) IT Italy (IT) Vivantes - Netzwerk für Gesundheit GmbH DE Germany (DE) Wrocław Medical University / Uniwersytet Medyczny we Wrocławiu PL Poland (PL) Vall d'Hebron University Hospital / Hospital Universitari Vall d'Hebron ES Spain (ES) Novartis Farma S.p.A IT Italy (IT) University of Paris 5 - René Descartes / Université Paris V René Descartes FR France (FR) University College London (UCL) GB United Kingdom (GB) Peking University (PKU) / 北京大学 CN China (CN) Tallinn Children’s Hospital EE Estonia (EE) Klinikverbund Kempten-Oberallgäu DE Germany (DE) University of Cape Town (UCT) ZA South Africa (ZA) Centro Hospitalar de Lisboa Ocidental E.P.E. (CHLO) PT Portugal (PT) Sydney Children’s Hospitals Network AU Australia (AU) Novartis AG CH Switzerland (CH) Shizuoka Institute of Epilepsy and Neurological Disorders JP Japan (JP) Centre Hospitalier Universitaire de Saint-Étienne (CHU) FR France (FR) "Aghia Sofia" General Children's Hospital GR Greece (GR) Paracelsus-Elena-Klinik Kassel DE Germany (DE) St George's, University of London (SGUL) / St George's Hospital Medical School GB United Kingdom (GB) Universitair Ziekenhuis Brussel BE Belgium (BE)

How to cite


De Vries, P.J., Belousova, E., Benedik, M.P., Carter, T., Cottin, V., Curatolo, P.,... Jansen, A.C. (2020). Natural clusters of tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND): new findings from the TOSCA TAND research project. Journal of Neurodevelopmental Disorders, 12(1).


De Vries, Petrus J., et al. "Natural clusters of tuberous sclerosis complex (TSC)-associated neuropsychiatric disorders (TAND): new findings from the TOSCA TAND research project." Journal of Neurodevelopmental Disorders 12.1 (2020).

BibTeX: Download