TSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study

dc.contributor.authorde Vries, Petrus J
dc.contributor.authorBelousova, Elena
dc.contributor.authorBenedik, Mirjana P
dc.contributor.authorCarter, Tom
dc.contributor.authorCottin, Vincent
dc.contributor.authorCuratolo, Paolo
dc.contributor.authorDahlin, Maria
dc.contributor.authorD’Amato, Lisa
dc.contributor.authord’Augères, Guillaume B
dc.contributor.authorFerreira, José C
dc.contributor.authorFeucht, Martha
dc.contributor.authorFladrowski, Carla
dc.contributor.authorHertzberg, Christoph
dc.contributor.authorJozwiak, Sergiusz
dc.contributor.authorKingswood, J. C
dc.contributor.authorLawson, John A
dc.contributor.authorMacaya, Alfons
dc.contributor.authorMarques, Ruben
dc.contributor.authorNabbout, Rima
dc.contributor.authorO’Callaghan, Finbar
dc.contributor.authorQin, Jiong
dc.contributor.authorSander, Valentin
dc.contributor.authorSauter, Matthias
dc.contributor.authorShah, Seema
dc.contributor.authorTakahashi, Yukitoshi
dc.contributor.authorTouraine, Renaud
dc.contributor.authorYouroukos, Sotiris
dc.contributor.authorZonnenberg, Bernard
dc.contributor.authorJansen, Anna C
dc.date.accessioned2018-09-17T13:05:31Z
dc.date.available2018-09-17T13:05:31Z
dc.date.issued2018-09-10
dc.date.updated2018-09-16T03:17:39Z
dc.description.abstractAbstract 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.apacitationde 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/11427/28477en_ZA
dc.identifier.chicagocitationde 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/11427/28477en_ZA
dc.identifier.citationOrphanet 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.urihttps://doi.org/10.1186/s13023-018-0901-8
dc.identifier.urihttp://hdl.handle.net/11427/28477
dc.identifier.vancouvercitationde 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.isoen
dc.publisherBioMed Central
dc.publisher.departmentDivision of Child and Adolescent Psychiatryen_ZA
dc.publisher.facultyFaculty of Health Sciencesen_ZA
dc.publisher.institutionUniversity of Cape Town
dc.rights.holderThe Author(s).
dc.sourceOrphanet Journal of Rare Diseases
dc.source.urihttps://ojrd.biomedcentral.com/
dc.subject.otherTSC-associated neuropsychiatric disorders
dc.subject.otherTuberous sclerosis complex
dc.subject.otherTOSCA
dc.titleTSC-associated neuropsychiatric disorders (TAND): findings from the TOSCA natural history study
dc.typeJournal Article
uct.type.filetypeText
uct.type.filetypeImage
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