Autismespectrumproblematiek bij erfelijke neurocognitieve ontwikkelingsstoornissen
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1 Autismespectrumproblematiek bij erfelijke neurocognitieve ontwikkelingsstoornissen Yulius congres Autisme: Transities in de sociale context Woensdag 18 november 2015 S.E. (Sabine) Mous, PhD Dep. of Child and Adolescent Psychiatry/Psychology Erasmus MC-Sophia, expertise center ENCORE
2 Disclosure (potentiële) belangenverstrengeling Voor bijeenkomst mogelijk relevante relaties met bedrijven Sponsoring of onderzoeksgeld Honorarium of andere (financiële) vergoeding Aandeelhouder Andere relatie, namelijk Geen / Zie hieronder Bedrijfsnamen
3 Overview 1) Syndromic ASD? 2) Expertise center ENCORE 3) Tuberous Sclerosis Complex 4) Fragile X syndrome 5) Angelman syndrome 6) Neurofibromatosis type I
4 Overview 1) Syndromic ASD? 2) Expertise center ENCORE 3) Tuberous Sclerosis Complex 4) Fragile X syndrome 5) Angelman syndrome 6) Neurofibromatosis type I
5 Syndromic ASD? When do you presume the presence of a syndrome? What do you do with this information? Pros and cons of knowing Bron: NVvP, 2009, Richtlijn diagnostiek en behandeling autismespectrumstoornissen bij kinderen en jeugdigen.
6 Syndromic ASD? Guideline NVvP Bron: NVvP, 2009, Richtlijn diagnostiek en behandeling autismespectrumstoornissen bij kinderen en jeugdigen.
7 Syndromic ASD? Bron: NVvP, 2009, Richtlijn diagnostiek en behandeling autismespectrumstoornissen bij kinderen en jeugdigen.
8 Syndromic ASD? Refer to clinical geneticist E.g. department of Clinical Genetics, Erasmus MC (part of Expertise center Encore) Check family history Physical examination: bodily/facial features Comprehensive chromosome analysis Explanation and counseling Study family carrier? Future children Own health (e.g. FXTAS/FXPOI)
9 Overview 1) Syndromic ASD? 2) Expertise center ENCORE 3) Tuberous Sclerosis Complex 4) Fragile X syndrome 5) Neurofibromatosis type I 6) Angelman syndrome
10 Expertise center ENCORE Multidisciplinary pooling of knowledge, care and scientific research for children with rare genetic neurodevelopmental disorders Multidisciplinary care Diagnosing Monitoring of problems & early interventions Application of novel treatments Enhancing prognosis and quality of life Scientific research Trials Data collected as part of standard patient care
11 Expertise centre ENCORE
12 Expertise center ENCORE Yearly follow-up by pediatrician At fixed ages cognitive/psychiatric follow-up by psychologist/psychiatrist Depending on disorder Neurologist Dermatologist Cardiologist Physiotherapist Speech therapist Dietician
13 Cognitive/psychiatric assessment Outpatient clinic Child and Adolescent Psychiatry/Psychology Fixed ages (~3, 7, 11 and 15 years) Knowledge regarding different problems at different ages Knowledge on development of problems over time If necessary; extra visits in between Fixed assessment protocol
14 Psychodiagnostic assessment Protocol: Questionnaires (e.g. behavioral problems, autistic traits, QoL) Intelligence assessment (WPPSI-III, WISC-III, WNV, BSID-III) Social interaction & communication, autistic traits (ADOS-2) Sometimes additional (neuro)psychological assessment Assessment by psychiatrist Information from parents and school
15 Why? Medical follow-up often prioritized However, neuropsychiatric manifestations represent substantial burden In depth assessment strengths and weaknesses Focused/personal advice Fitting treatment
16 Overview 1) Syndromic ASD? 2) Expertise center ENCORE 3) Tuberous Sclerosis Complex 4) Fragile X syndrome 5) Angelman syndrome 6) Neurofibromatosis type I
17 Tuberous Sclerosis Complex (TSC) Living with TSC: Flor s family vacation
18 Tuberous Sclerosis Complex (TSC) Hannah talking about Tuberous Sclerosis
19 Tuberous Sclerosis Complex (TSC) Prevalence 1:6,000 Autosomal dominant disorder However, most cases sporadic cases Mutation TSC1 or TSC2 gene Decrease in hamartin/tuberin protein Hyperactivation of the mtor pathway Abnormal/uncontrolled cell growth Multi-systemic disorder Brain Skin, heart, kidneys (, teeth, bones, eyes)
20 Tuberous Sclerosis Complex (TSC) Bodily/facial characteristics Hypomelanotic Macules (ash leaf spots) Facial angiofibromas Shagreen patch Ungual fibromas
21 Tuberous Sclerosis Complex (TSC) Tubers, SENs, SEGAs Cortical tubers: ~80% Subependymal nodules: ~50% Subependymal giant cell astrocytomas: ~10-15% Epilepsy: ~90%
22 Intelligence Cognitive functioning large individual differences Depending on mutation (TSC1/TSC2) Intellectual disability: ~50% (IQ<70) Dark grey = TSC1 Shaded grey = TSC2 Light Grey = no mutation identified van Eeghen et al, 2012
23 Intelligence Preliminary work, unpublished VIQ and PIQ in this sample both average ~80
24 Intelligence and tubers O Callaghan et al, 2004
25 TSC-associated neuropsychiatric disorders Curatolo et al, 2015
26 Behavioral/psychiatric problems Autism spectrum disorder: ~40-50% Attention problems and hyperactivity: ~30-50% Anxiety disorder: ~30-60% Depressive disorder: ~30-40%
27 ADOS Preliminary work, unpublished
28 ADOS and IQ Totaal IQ Verbaal IQ Performaal IQ ADOS-G Totaal Pearson Correlation -,450* -,419* -,468* Sig. (2-tailed) 0,011 0,042 0,021 N ADOS-G Taal/communicatie Pearson Correlation -,418* -,443* -,443* Sig. (2-tailed) 0,022 0,034 0,034 N ADOS-G Wederkerige sociale interactie Pearson Correlation -,445* -,417* -,448* Sig. (2-tailed) 0,014 0,048 0,032 N ADOS-G Fantasie en creativiteit Pearson Correlation -0,126-0,246-0,149 Sig. (2-tailed) 0,508 0,257 0,498 N ADOS-G Stereotiepe gedragingen/beperkte interesses Pearson Correlation -0,169-0,119-0,149 Sig. (2-tailed) 0,372 0,589 0,496 N ** Correlation is significant at the 0.01 level (2-tailed). * Correlation is significant at the 0.05 level (2-tailed). Preliminary work, unpublished
29 ADOS and mutation n=12 n=21 Preliminary work, unpublished
30 Mean t-score Social Responsiveness Scale (SRS) N=30 (16 male, 14 female) ,5 74,2 71,2 74, , , Total Social Affect Social Cognition Social Communication Social Motivation Autistic Manners Preliminary work, unpublished
31 Social Responsiveness Scale (SRS) 60% 50% 50% 50% 43% 40% 40% 40% 40% 33% 33% 33% 30% 30% 27% 27% 27% 23% 30% 30% 27% normal (t <= 60) mild-moderate problems (t = 61-75) severe problems (t >= 76) 20% 17% 10% 0% Total Social Affect Social Cognition Social Communication Social Motivation Autistic Manners Preliminary work, unpublished
32 DSM-IV diagnoses 2/3 of all children receive a diagnosis, ~1/3 no psychiatric diagnosis Of the children with a diagnosis: DSM-IV primaire diagnose (as I, klinische aandoening) Aantal keer gesteld % Autistic Disorder 12 32% Pervasive Developmental Disorder NOS (PDD-NOS/ASD) 12 32% Attention-Deficit Hyperactivity Disorder Combined subtype 3 8% Attention-Deficit Hyperactivity Disorder Predominantly inattentive subtype 2 5% Disorder of infancy, childhood, or adolescence NOS 2 5% Attention-Deficit Hyperactivity Disorder NOS 1 3% F91.8 Conduct disorder 1 3% Reading disorder 1 3% Stuttering 1 3% Dysthymic disorder 1 3% Major depressive disorder, single episode, In partial remission 1 3% TOTAAL % Underestimation ADHD, due to ASD diagnosis!
33 ENCORE TSC-RAPIT trial Prospective randomized double-blind placebo-controlled clinical trial 60 patients with TSC aged 4-17 years Effect of everolimus on autism spectrum problems (ASD) and neuropsychological functioning in TSC ASD IQ Spatial working memory Sustained attention.
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