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

Romina Moavero, Arianna Benvenuto, Leonardo Emberti Gialloreti, Martina Siracusano, Katarzyna Kotulska, Bernhard Weschke, Kate Riney, Floor E Jansen, Martha Feucht, Pavel Krsek, Rima Nabbout, Anna C Jansen, Konrad Wojdan, Julita Borkowska, Krzystof Sadowski, Christoph Hertzberg, Hanna Hulshof, Sharon Samueli, Barbora Benova, Eleonora AronicaDavid J Kwiatkowski, Lieven Lagae, Sergiusz Jozwiak, Paolo Curatolo

Research output: Contribution to journalArticle

Abstract

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.

Original languageEnglish
JournalJournal of Clinical Medicine
Volume8
Issue number6
DOIs
Publication statusPublished - Jun 3 2019

Fingerprint

Tuberous Sclerosis
Biomarkers
Stereotyped Behavior
Genetic Models
Autistic Disorder
Child Development
Autism Spectrum Disorder
Early Diagnosis
Epilepsy
Appointments and Schedules
Communication
Observation
Prospective Studies

Cite this

Early Clinical Predictors of Autism Spectrum Disorder in Infants with Tuberous Sclerosis Complex : Results from the EPISTOP Study. / Moavero, Romina; Benvenuto, Arianna; Emberti Gialloreti, Leonardo; Siracusano, Martina; Kotulska, Katarzyna; Weschke, Bernhard; Riney, Kate; Jansen, Floor E; Feucht, Martha; Krsek, Pavel; Nabbout, Rima; Jansen, Anna C; Wojdan, Konrad; Borkowska, Julita; Sadowski, Krzystof; Hertzberg, Christoph; Hulshof, Hanna; Samueli, Sharon; Benova, Barbora; Aronica, Eleonora; Kwiatkowski, David J; Lagae, Lieven; Jozwiak, Sergiusz; Curatolo, Paolo.

In: Journal of Clinical Medicine, Vol. 8, No. 6, 03.06.2019.

Research output: Contribution to journalArticle

Moavero, R, Benvenuto, A, Emberti Gialloreti, L, Siracusano, M, Kotulska, K, Weschke, B, Riney, K, Jansen, FE, Feucht, M, Krsek, P, Nabbout, R, Jansen, AC, Wojdan, K, Borkowska, J, Sadowski, K, Hertzberg, C, Hulshof, H, Samueli, S, Benova, B, Aronica, E, Kwiatkowski, DJ, Lagae, L, Jozwiak, S & Curatolo, P 2019, 'Early Clinical Predictors of Autism Spectrum Disorder in Infants with Tuberous Sclerosis Complex: Results from the EPISTOP Study', Journal of Clinical Medicine, vol. 8, no. 6. https://doi.org/10.3390/jcm8060788
Moavero, Romina ; Benvenuto, Arianna ; Emberti Gialloreti, Leonardo ; Siracusano, Martina ; Kotulska, Katarzyna ; Weschke, Bernhard ; Riney, Kate ; Jansen, Floor E ; Feucht, Martha ; Krsek, Pavel ; Nabbout, Rima ; Jansen, Anna C ; Wojdan, Konrad ; Borkowska, Julita ; Sadowski, Krzystof ; Hertzberg, Christoph ; Hulshof, Hanna ; Samueli, Sharon ; Benova, Barbora ; Aronica, Eleonora ; Kwiatkowski, David J ; Lagae, Lieven ; Jozwiak, Sergiusz ; Curatolo, Paolo. / Early Clinical Predictors of Autism Spectrum Disorder in Infants with Tuberous Sclerosis Complex : Results from the EPISTOP Study. In: Journal of Clinical Medicine. 2019 ; Vol. 8, No. 6.
@article{74c8621ebc6b4aa4a14a8e849fd782a1,
title = "Early Clinical Predictors of Autism Spectrum Disorder in Infants with Tuberous Sclerosis Complex: Results from the EPISTOP Study",
abstract = "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.",
author = "Romina Moavero and Arianna Benvenuto and {Emberti Gialloreti}, Leonardo and Martina Siracusano and Katarzyna Kotulska and Bernhard Weschke and Kate Riney and Jansen, {Floor E} and Martha Feucht and Pavel Krsek and Rima Nabbout and Jansen, {Anna C} and Konrad Wojdan and Julita Borkowska and Krzystof Sadowski and Christoph Hertzberg and Hanna Hulshof and Sharon Samueli and Barbora Benova and Eleonora Aronica and Kwiatkowski, {David J} and Lieven Lagae and Sergiusz Jozwiak and Paolo Curatolo",
year = "2019",
month = "6",
day = "3",
doi = "10.3390/jcm8060788",
language = "English",
volume = "8",
journal = "Journal of Clinical Medicine",
issn = "2077-0383",
publisher = "Multidisciplinary Digital Publishing Institute (MDPI)",
number = "6",

}

TY - JOUR

T1 - Early Clinical Predictors of Autism Spectrum Disorder in Infants with Tuberous Sclerosis Complex

T2 - Results from the EPISTOP Study

AU - Moavero, Romina

AU - Benvenuto, Arianna

AU - Emberti Gialloreti, Leonardo

AU - Siracusano, Martina

AU - Kotulska, Katarzyna

AU - Weschke, Bernhard

AU - Riney, Kate

AU - Jansen, Floor E

AU - Feucht, Martha

AU - Krsek, Pavel

AU - Nabbout, Rima

AU - Jansen, Anna C

AU - Wojdan, Konrad

AU - Borkowska, Julita

AU - Sadowski, Krzystof

AU - Hertzberg, Christoph

AU - Hulshof, Hanna

AU - Samueli, Sharon

AU - Benova, Barbora

AU - Aronica, Eleonora

AU - Kwiatkowski, David J

AU - Lagae, Lieven

AU - Jozwiak, Sergiusz

AU - Curatolo, Paolo

PY - 2019/6/3

Y1 - 2019/6/3

N2 - 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.

AB - 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.

U2 - 10.3390/jcm8060788

DO - 10.3390/jcm8060788

M3 - Article

C2 - 31163675

VL - 8

JO - Journal of Clinical Medicine

JF - Journal of Clinical Medicine

SN - 2077-0383

IS - 6

ER -