TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study
dc.contributor.author | de Vries, Petrus J | |
dc.contributor.author | Belousova, Elena | |
dc.contributor.author | Benedik, Mirjana P | |
dc.contributor.author | Carter, Tom | |
dc.contributor.author | Cottin, Vincent | |
dc.contributor.author | Curatolo, Paolo | |
dc.contributor.author | Dahlin, Maria | |
dc.contributor.author | D’Amato, Lisa | |
dc.contributor.author | d’Augères, Guillaume B | |
dc.contributor.author | Ferreira, José C | |
dc.contributor.author | Feucht, Martha | |
dc.contributor.author | Fladrowski, Carla | |
dc.contributor.author | Hertzberg, Christoph | |
dc.contributor.author | Jozwiak, Sergiusz | |
dc.contributor.author | Kingswood, J. C | |
dc.contributor.author | Lawson, John A | |
dc.contributor.author | Macaya, Alfons | |
dc.contributor.author | Marques, Ruben | |
dc.contributor.author | Nabbout, Rima | |
dc.contributor.author | O’Callaghan, Finbar | |
dc.contributor.author | Qin, Jiong | |
dc.contributor.author | Sander, Valentin | |
dc.contributor.author | Sauter, Matthias | |
dc.contributor.author | Shah, Seema | |
dc.contributor.author | Takahashi, Yukitoshi | |
dc.contributor.author | Touraine, Renaud | |
dc.contributor.author | Youroukos, Sotiris | |
dc.contributor.author | Zonnenberg, Bernard | |
dc.contributor.author | Jansen, Anna C | |
dc.date.accessioned | 2018-09-17T13:05:31Z | |
dc.date.available | 2018-09-17T13:05:31Z | |
dc.date.issued | 2018-09-10 | |
dc.date.updated | 2018-09-16T03:17:39Z | |
dc.description.abstract | Abstract Background Most evidence for TSC-associated neuropsychiatric disorders (TAND) to date have come from small studies and case reports, and very little is known about TAND in adults. We explored baseline TAND data from the large-scale international TOSCA natural history study to compare childhood and adult patterns, describe age-based patterns, and explore genotype-TAND correlations. Results The study enrolled 2216 eligible participants with TSC from 170 sites across 31 countries at the data cut-off for the third interim analysis (data cut-off date: September 30, 2015). The most common behavioural problems (reported in > 10% of participants) were overactivity, sleep difficulties, impulsivity, anxiety, mood swings, severe aggression, depressed mood, self-injury, and obsessions. Psychiatric disorders included autism spectrum disorder (ASD, 21.1%), attention deficit hyperactivity disorder (ADHD, 19.1%), anxiety disorder (9.7%), and depressive disorder (6.1%). Intelligence quotient (IQ) scores were available for 885 participants. Of these, 44.4% had normal IQ, while mild, moderate, severe, and profound degrees of intellectual disability (ID) were observed in 28.1, 15.1, 9.3, and 3.1%, respectively. Academic difficulties were identified in 58.6% of participants, and neuropsychological deficits (performance <5th percentile) in 55.7%. Significantly higher rates of overactivity and impulsivity were observed in children and higher rates of anxiety, depressed mood, mood swings, obsessions, psychosis and hallucinations were observed in adults. Genotype-TAND correlations showed a higher frequency of self-injury, ASD, academic difficulties and neuropsychological deficits in TSC2. Those with no mutations identified (NMI) showed a mixed pattern of TAND manifestations. Children and those with TSC2 had significantly higher rates of intellectual disability, suggesting that age and genotype comparisons should be interpreted with caution. Conclusions These results emphasize the magnitude of TAND in TSC and the importance of evaluating for neuropsychiatric comorbidity in all children and adults with TSC, across TSC1 and TSC2 genotypes, as well as in those with no mutations identified. However, the high rates of unreported or missing TAND data in this study underline the fact that, even in expert centres, TAND remains underdiagnosed and potentially undertreated. | |
dc.identifier.apacitation | de Vries, P. J., Belousova, E., Benedik, M. P., Carter, T., Cottin, V., Curatolo, P., ... Jansen, A. C. (2018). TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study. <i>Orphanet Journal of Rare Diseases</i>, http://hdl.handle.net/11427/28477 | en_ZA |
dc.identifier.chicagocitation | de Vries, Petrus J, Elena Belousova, Mirjana P Benedik, Tom Carter, Vincent Cottin, Paolo Curatolo, Maria Dahlin, et al "TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study." <i>Orphanet Journal of Rare Diseases</i> (2018) http://hdl.handle.net/11427/28477 | en_ZA |
dc.identifier.citation | Orphanet Journal of Rare Diseases. 2018 Sep 10;13(1):157 | |
dc.identifier.ris | TY - Journal Article AU - de Vries, Petrus J AU - Belousova, Elena AU - Benedik, Mirjana P AU - Carter, Tom AU - Cottin, Vincent AU - Curatolo, Paolo AU - Dahlin, Maria AU - D’Amato, Lisa AU - d’Augères, Guillaume B AU - Ferreira, José C AU - Feucht, Martha AU - Fladrowski, Carla AU - Hertzberg, Christoph AU - Jozwiak, Sergiusz AU - Kingswood, J. C AU - Lawson, John A AU - Macaya, Alfons AU - Marques, Ruben AU - Nabbout, Rima AU - O’Callaghan, Finbar AU - Qin, Jiong AU - Sander, Valentin AU - Sauter, Matthias AU - Shah, Seema AU - Takahashi, Yukitoshi AU - Touraine, Renaud AU - Youroukos, Sotiris AU - Zonnenberg, Bernard AU - Jansen, Anna C AB - Abstract Background Most evidence for TSC-associated neuropsychiatric disorders (TAND) to date have come from small studies and case reports, and very little is known about TAND in adults. We explored baseline TAND data from the large-scale international TOSCA natural history study to compare childhood and adult patterns, describe age-based patterns, and explore genotype-TAND correlations. Results The study enrolled 2216 eligible participants with TSC from 170 sites across 31 countries at the data cut-off for the third interim analysis (data cut-off date: September 30, 2015). The most common behavioural problems (reported in > 10% of participants) were overactivity, sleep difficulties, impulsivity, anxiety, mood swings, severe aggression, depressed mood, self-injury, and obsessions. Psychiatric disorders included autism spectrum disorder (ASD, 21.1%), attention deficit hyperactivity disorder (ADHD, 19.1%), anxiety disorder (9.7%), and depressive disorder (6.1%). Intelligence quotient (IQ) scores were available for 885 participants. Of these, 44.4% had normal IQ, while mild, moderate, severe, and profound degrees of intellectual disability (ID) were observed in 28.1, 15.1, 9.3, and 3.1%, respectively. Academic difficulties were identified in 58.6% of participants, and neuropsychological deficits (performance <5th percentile) in 55.7%. Significantly higher rates of overactivity and impulsivity were observed in children and higher rates of anxiety, depressed mood, mood swings, obsessions, psychosis and hallucinations were observed in adults. Genotype-TAND correlations showed a higher frequency of self-injury, ASD, academic difficulties and neuropsychological deficits in TSC2. Those with no mutations identified (NMI) showed a mixed pattern of TAND manifestations. Children and those with TSC2 had significantly higher rates of intellectual disability, suggesting that age and genotype comparisons should be interpreted with caution. Conclusions These results emphasize the magnitude of TAND in TSC and the importance of evaluating for neuropsychiatric comorbidity in all children and adults with TSC, across TSC1 and TSC2 genotypes, as well as in those with no mutations identified. However, the high rates of unreported or missing TAND data in this study underline the fact that, even in expert centres, TAND remains underdiagnosed and potentially undertreated. DA - 2018-09-10 DB - OpenUCT DP - University of Cape Town J1 - Orphanet Journal of Rare Diseases LK - https://open.uct.ac.za PB - University of Cape Town PY - 2018 T1 - TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study TI - TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study UR - http://hdl.handle.net/11427/28477 ER - | en_ZA |
dc.identifier.uri | https://doi.org/10.1186/s13023-018-0901-8 | |
dc.identifier.uri | http://hdl.handle.net/11427/28477 | |
dc.identifier.vancouvercitation | de Vries PJ, Belousova E, Benedik MP, Carter T, Cottin V, Curatolo P, et al. TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study. Orphanet Journal of Rare Diseases. 2018; http://hdl.handle.net/11427/28477. | en_ZA |
dc.language.iso | en | |
dc.publisher | BioMed Central | |
dc.publisher.department | Division of Child and Adolescent Psychiatry | en_ZA |
dc.publisher.faculty | Faculty of Health Sciences | en_ZA |
dc.publisher.institution | University of Cape Town | |
dc.rights.holder | The Author(s). | |
dc.source | Orphanet Journal of Rare Diseases | |
dc.source.uri | https://ojrd.biomedcentral.com/ | |
dc.subject.other | TSC-associated neuropsychiatric disorders | |
dc.subject.other | Tuberous sclerosis complex | |
dc.subject.other | TOSCA | |
dc.title | TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study | |
dc.type | Journal Article | |
uct.type.filetype | Text | |
uct.type.filetype | Image |