ICNC Abstracts, ICNC 2018

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Tuberous Sclerosis Complex (TSC)-Associated Neuropsychiatric Disorders (TAND): New Findings on Age, Gender and Genotype in Relation to Intellectual Phenotype
Petrus J De Vries, Elena Belousova, Mirjana P Benedik, Tom Carter, Vincent Cottin, Paolo Curatolo, Maria Dahlin, Lisa D´Amato, Guillaume B d'Augères, 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, Matthias Sauter, Seema Shah, Yukitoshi Takahashi, Renaud Touraine, Sotiris Youroukos, Bernard Zonnenberg, John C Kingswood, Anna C Jansen

Last modified: 2018-09-09


Introduction: We previously reported baseline data on tuberous sclerosis complex (TSC)-Associated Neuropsychiatric Disorders (TAND) from the TOSCA study, and described age- and genotype-related patterns. Here we examined TAND profiles across age, sex and genotype in relation to level of intellectual ability (IA).

Methods: Using the TOSCA final analysis baseline data, the association between age (children versus adults), gender, and genotype (TSC1 versus TSC2) stratified by IA (IQ>70=no intellectual disability (ID); IQ:50-70=mild ID; IQ<50=moderate-profound ID) were analysed using the Cochran–Mantel–Haenszel test. Statistical significance was set at <0.01.

Results: IQ data were available for 894/2211 patients from TOSCA. Most behavioural difficulties showed significant association with the level of IA, except depressed mood, anxiety and hallucinations. IA showed significant association with autism spectrum disorder (ASD), attention deficit hyperactivity disorder (ADHD) and other psychiatric disorders, but not with depressive (P=0.2258) or anxiety disorder (P=0.6506). Children showed more behavioural difficulties (except sleep and impulsivity), ADHD and anxiety disorders, and adults showed more depression, hallucinations, psychosis and depressive disorders. Males had more impulsivity, overactivity, obsessions, ASD and ADHD. Academic difficulties and neuropsychological deficits were significantly associated with IA, but not with age or sex. No genotype-TAND associations were seen after controlling for IA.

Conclusions: The TOSCA study confirmed the association between level of IA and TAND manifestations, suggesting IA as risk marker for most TAND manifestations. These findings provide the first evidence of male preponderance of ASD and ADHD in TSC, and disproves the previously-reported TSC2 association with ASD and other TAND.


Tuberous sclerosis complex-Associated Neuropsychiatric Disorders; intellectual ability; TOSCA; Intellectual disability

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