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The Prevalence of Autism Spectrum Disorder (ASD) and Attention Deficit Hyperactivity Disorder (ADHD) in Tuberous Sclerosis Complex (TSC). a Comparison of Prevalence in Patients with TSC1 and TSC2 Mutations.

Poster Presentation
Friday, May 3, 2019: 5:30 PM-7:00 PM
Room: 710 (Palais des congres de Montreal)
W. Y. Cheung1, Y. Shen2, C. Tye3, F. S. McEwen4, L. Underwood5, E. L. Woodhouse6, F. Sheerin7, N. Higgins8, H. L. Liang2,9, E. Shephard10, J. Yates11, P. Bolton3, J. W. Steenbruggen2 and E. Barker12, (1)Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, london, United Kingdom, (2)Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom, (3)Department of Child & Adolescent Psychiatry, Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom, (4)Biological and Experimental Psychology, Queen Mary University of London, London, United Kingdom, (5)Psychological Medicine, University of Auckland, Auckland, New Zealand, (6)Forensic & Neurodevelopmental Sciences, Institute of Psychiatry, Psychology & Neuroscience, London, United Kingdom, (7)Department of Neuroradiology, Oxford University Hospital NHS Foundation Trust, Oxford, United Kingdom, (8)Department of Radiology, Addenbrooke’s Hospital, Cambridge, United Kingdom, (9)South London and Maudsley NHS Trust, London, United Kingdom, (10)Institute of Psychiatry, Psychology and Neuroscience, King's College London, London, United Kingdom of Great Britain and Northern Ireland, (11)Department of Medical Genetics, Cambridge University, Cambridge, United Kingdom, (12)Department of Psychology, Institute of Psychiatry, Psychology & Neuroscience, King’s College London, London, United Kingdom
Background:

Tuberous Sclerosis Complex (TSC) is an autosomal genetic disorder caused by mutations in the TSC1 or TSC2 genes. Several reports indicate that compared with TSC2 mutations, TSC1 gene mutations present with less severe physical phenotype. However, although TSC is well established as a cause of ASD and ADHD, it is not known if the risk of ASD or ADHD also differs according to whether the TSC1 or TSC2 gene is mutated.

Objectives:

To determine the prevalence of ASD and ADHD based on mutation type (TSC1 or TSC2 gene) and to investigate the correlates of the psychopathological manifestations in TSC1 and TSC2 cases (e.g. tuber count, epilepsy severity etc).

Methods:

This study uses data from the TS2000 study, the first population based, longitudinal study of the natural history of TSC. 125 children aged 0-16 years diagnosed with TS were ascertained. Baseline measures of epilepsy severity, intellectual ability, cortical tuber count and genetic testing were undertaken. Participants were followed up and assessed using standardised and semi-standardised measures of ASD and ADHD. This include Autism Diagnostic Observation Scale (ADOS), Autism Diagnostic Interview- Revised (ADI-R) for ASD, Strength and Difficulties Questionnaires (SDQ), The Development and Well-Being Assessment (DAWBA), Diagnostic Interview for ADHD (DIVA) or Kiddie Schedule for Affective Disorders and Schizophrenia (KSADS) for ADHD.

Results:

  1. a) Of the 125 participants, 19 had TSC1 mutations and 77 had TSC2 mutations.
  2. b) 42.9% of patients with TSC2 mutation met stringent diagnostic criteria for ASD, a further 24.5% met criteria for probable ASD and another 12.2% for more broadly defined ASD . Amongst patients with TSC1 mutations, 25% met stringent diagnostic criteria for ASD, 37.5% probable ASD and 18.8% met criteria for the more broadly defined autism spectrum disorder phenotype. The difference in prevalence between TSC1 and TSC2 cases was not statistically significant (p= 0.77).
  3. c) Patients with TSC1 mutation had a slightly higher rate of definite ADHD diagnosis (27.3%) as compared to patients with TSC2 mutation (20.8%). A further 22.9% of participants with TSC2 mutation met criteria for probable ADHD as compared to 9.1% of TSC1 mutation cases. Again, the differences were not statistically significant (p=0.70).

Conclusions:

Mutations in both the TSC1 and TSC2 genes are associated with an increased risk of ASD and ADHD compared to the general population, but in this small sample, the prevalence of ASD and ADHD in TSC1 and TSC2 cases was not significantly different.

See more of: Clinical Genetics
See more of: Clinical Genetics