Early Clinical Predictors of Autism Spectrum Disorder in Infants with Tuberous Sclerosis Complex: Results from the EPISTOP Study

Journal of Clinical Medicine

Eleonora Aronica¹  David J. Kwiatkowski²  Paolo Curatolo³  Romina Moavero³  Arianna Benvenuto³  Leonardo Emberti Gialloreti⁴  Martina Siracusano⁴  Floor E. Jansen⁵  Hanna Hulshof⁵  Bernhard Weschke⁶  Lieven Lagae⁷  Julita Borkowska⁸  Sergiusz Jozwiak⁸  Krzystof Sadowski⁸  Katarzyna Kotulska⁸  Rima Nabbout⁹  Sharon Samueli^1,10  Martha Feucht^1,10  Christoph Hertzberg^1,11  on behalf of the EPISTOP Consortium^1,12  Pavel Krsek^1,13  Barbora Benova^1,13  Kate Riney^1,14  Anna C. Jansen^1,15  Konrad Wojdan^1,16 

[1] Amsterdam UMC, University of Amsterdam, Department of (Neuro)Pathology, Amsterdam Neuroscience, Meibergdreef 9, 1105 AZ Amsterdam, The Netherlands;Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA;Child Neurology and Psychiatry Unit, Systems Medicine Department, Tor Vergata University, Via Montpellier 1, 00133 Rome, Italy;Department of Biomedicine and Prevention, Tor Vergata University of Rome, Via Montpellier 1, 00133 Rome, Italy;Department of Child Neurology, Brain Center, University Medical Center Utrecht, 3584 Utrecht, The Netherlands;Department of Child Neurology, Charité University Medicine Berlin, Augustenburger Platz 1, 13353 Berlin, Germany;Department of Development and Regeneration-Section Pediatric Neurology, University Hospitals KU Leuven, 3000 Leuven, Belgium;Department of Neurology and Epileptology, The Children’s Memorial Health Institute, Al. Dzieci Polskich 20, 04-730 Warsaw, Poland;Department of Pediatric Neurology, Reference Centre for Rare Epilepsies, Necker- Enfants Malades Hospital, University Paris Descartes, Imagine Institute, 75015 Paris, France;Department of Pediatrics, University Hospital Vienna, 1090 Vienna, Austria;Diagnose und Behandlungszentrum für Kinder und Jugendliche, Vivantes Klinikum Neuköln, 12351 Berlin, Germany;J. Anink, M. Blazejczyk, A. Bongaerts, J. Borkowska, D. Breuillard, D. Chmielewski, M. Dabrowska, J. De Ridder, K. Giannikou, J. Glowacka, L. Hamieh, A. Haręza, A. Iyer, Bart Janssen, J. Jaworski, M. Kaczorowska- Frontczak, K. Lehmann, A. Leusman, N. Maćkowiak, J. Mills, A. Muelebner, C. Scheldeman, A. Sciuto, K. Sijko, M. Slowinska, A. Tempes, J. van Scheppingen, B. Verhelle, J. Vervisch, M. Urbańska, K. Zych, M. Biernacka, B. Łojszczyk.;Motol University Hospital, Charles University, 150 06 Prague, Czech Republic;Neuroscience Unit, Queensland Children’s Hospital, 501 Stanley Street, South Brisbane, QLD 4101, Australia;Pediatric Neurology Unit-UZ Brussel, 1050 Brussels, Belgium;Warsaw University of Technology, Institute of Heat Engineering, 00-661 Warsaw, Poland;

关键词: tuberous sclerosis complex;    autism;    EPISTOP;    treatment;    markers;    epilepsy;    risk factors;    developmental delay;    intellectual disability;    diagnosis;   

DOI  :  10.3390/jcm8060788

来源: DOAJ

【 摘 要 】

Autism spectrum disorder (ASD) is highly prevalent in subjects with Tuberous Sclerosis Complex (TSC), but we are not still able to reliably predict which infants will develop ASD. This study aimed to identify the early clinical markers of ASD and/or developmental delay (DD) in infants with an early diagnosis of TSC. We prospectively evaluated 82 infants with TSC (6–24 months of age), using a detailed neuropsychological assessment (Bayley Scales of Infant Development—BSID, and Autism Diagnostic Observation Schedule—ADOS), in the context of the EPISTOP (Long-term, prospective study evaluating clinical and molecular biomarkers of EPIleptogenesiS in a genetic model of epilepsy—Tuberous SclerOsis ComPlex) project (NCT02098759). Normal cognitive developmental quotient at 12 months excluded subsequent ASD (negative predictive value 100%). The total score of ADOS at 12 months clearly differentiated children with a future diagnosis of ASD from children without (p = 0.012). Atypical socio-communication behaviors (p < 0.001) were more frequently observed than stereotyped/repetitive behaviors in children with ASD at 24 months. The combined use of BSID and ADOS can reliably identify infants with TSC with a higher risk for ASD at age 6–12 months, allowing for clinicians to target the earliest symptoms of abnormal neurodevelopment with tailored intervention strategies.

【 授权许可】

Unknown