Contrasting Relationships Between Anxiety and Intolerance of Uncertainty in Cornelia de Lange and Fragile X Syndromes

Kayla Smith; Victoria Perry; Laura Groves; Joanna Moss; Chris Oliver; Eve Knight; Tom Patterson; Jacqui Rodgers; Jane Waite; Hayley Crawford

doi:10.1111/jir.70024

Contrasting Relationships Between Anxiety and Intolerance of Uncertainty in Cornelia de Lange and Fragile X Syndromes

Kayla Smith, Victoria Perry, Laura Groves, Joanna Moss, Chris Oliver, Eve Knight, Tom Patterson, Jacqui Rodgers, Jane Waite, Hayley Crawford^*

^*Corresponding author for this work

Cerebra Network for Neurodevelopmental Disorders, University of Birmingham, Birmingham, UK.
School of Psychological, Social and Behavioural Sciences Coventry University Coventry UK
School of Psychology, University of Birmingham
School of Psychology, University of Surrey, Guildford, England
Population Health Sciences Institute, Sir James Spence Institute Newcastle University, Royal Victoria Infirmary Newcastle Upon Tyne UK

Research output: Contribution to journal › Article › peer-review

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Abstract

Background: Cornelia de Lange syndrome (CdLS) and fragile X syndrome (FXS) are associated with co‐occurring autism and anxiety. In autistic people, intolerance of uncertainty (IU) mediates the relationship between autistic characteristics and anxiety, but it is not known whether this relationship is evident in these genetic syndromes. Understanding the relationship between autism, anxiety and IU is essential to informing the theoretical frameworks of anxiety in rare genetic syndromes and improving clinical interventions.

Method: Sixty participants with CdLS or FXS participated in a questionnaire‐based study to examine the association between autistic characteristics, anxiety and IU.

Results: IU mediated the association between autism and anxiety in participants with CdLS but not in participants with FXS.

Conclusions: These results suggest that other factors may contribute to the autism‐anxiety relationship in FXS, and highlight the merit of syndrome‐specific approaches to the study of anxiety. Recommendations are made for intervention‐based research to ameliorate anxiety in CdLS.

Original language	English
Pages (from-to)	1370-1381
Number of pages	12
Journal	Journal of Intellectual Disability Research
Volume	69
Issue number	12
Early online date	29 Aug 2025
DOIs	https://doi.org/10.1111/jir.70024
Publication status	E-pub ahead of print - 29 Aug 2025

Bibliographical note

Copyright © 2025 The Author(s). Journal of Intellectual Disability Research published by MENCAP and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Keywords

anxiety
autism
intellectual disability
fragile X syndrome
Cornelia de Lange syndrome
intolerance of uncertainty

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10.1111/jir.70024Licence: CC BY 4.0

Contrasting Relationships Between Anxiety and Intolerance of Uncertainty in Cornelia de Lange and Fragile X Syndromes
Copyright © 2025 The Author(s). Journal of Intellectual Disability Research published by MENCAP and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Final published version, 650 KBLicence: CC BY 4.0

Cite this

Smith, K., Perry, V., Groves, L., Moss, J., Oliver, C., Knight, E., Patterson, T., Rodgers, J., Waite, J., & Crawford, H. (2025). Contrasting Relationships Between Anxiety and Intolerance of Uncertainty in Cornelia de Lange and Fragile X Syndromes. Journal of Intellectual Disability Research, 69(12), 1370-1381. Advance online publication. https://doi.org/10.1111/jir.70024

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title = "Contrasting Relationships Between Anxiety and Intolerance of Uncertainty in Cornelia de Lange and Fragile X Syndromes",

abstract = "Background: Cornelia de Lange syndrome (CdLS) and fragile X syndrome (FXS) are associated with co‐occurring autism and anxiety. In autistic people, intolerance of uncertainty (IU) mediates the relationship between autistic characteristics and anxiety, but it is not known whether this relationship is evident in these genetic syndromes. Understanding the relationship between autism, anxiety and IU is essential to informing the theoretical frameworks of anxiety in rare genetic syndromes and improving clinical interventions. Method: Sixty participants with CdLS or FXS participated in a questionnaire‐based study to examine the association between autistic characteristics, anxiety and IU. Results: IU mediated the association between autism and anxiety in participants with CdLS but not in participants with FXS. Conclusions: These results suggest that other factors may contribute to the autism‐anxiety relationship in FXS, and highlight the merit of syndrome‐specific approaches to the study of anxiety. Recommendations are made for intervention‐based research to ameliorate anxiety in CdLS.",

keywords = "anxiety, autism, intellectual disability, fragile X syndrome, Cornelia de Lange syndrome, intolerance of uncertainty",

author = "Kayla Smith and Victoria Perry and Laura Groves and Joanna Moss and Chris Oliver and Eve Knight and Tom Patterson and Jacqui Rodgers and Jane Waite and Hayley Crawford",

note = "Copyright {\textcopyright} 2025 The Author(s). Journal of Intellectual Disability Research published by MENCAP and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.",

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AU - Oliver, Chris

AU - Knight, Eve

AU - Patterson, Tom

AU - Rodgers, Jacqui

AU - Waite, Jane

AU - Crawford, Hayley

N1 - Copyright © 2025 The Author(s). Journal of Intellectual Disability Research published by MENCAP and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

PY - 2025/8/29

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N2 - Background: Cornelia de Lange syndrome (CdLS) and fragile X syndrome (FXS) are associated with co‐occurring autism and anxiety. In autistic people, intolerance of uncertainty (IU) mediates the relationship between autistic characteristics and anxiety, but it is not known whether this relationship is evident in these genetic syndromes. Understanding the relationship between autism, anxiety and IU is essential to informing the theoretical frameworks of anxiety in rare genetic syndromes and improving clinical interventions. Method: Sixty participants with CdLS or FXS participated in a questionnaire‐based study to examine the association between autistic characteristics, anxiety and IU. Results: IU mediated the association between autism and anxiety in participants with CdLS but not in participants with FXS. Conclusions: These results suggest that other factors may contribute to the autism‐anxiety relationship in FXS, and highlight the merit of syndrome‐specific approaches to the study of anxiety. Recommendations are made for intervention‐based research to ameliorate anxiety in CdLS.

AB - Background: Cornelia de Lange syndrome (CdLS) and fragile X syndrome (FXS) are associated with co‐occurring autism and anxiety. In autistic people, intolerance of uncertainty (IU) mediates the relationship between autistic characteristics and anxiety, but it is not known whether this relationship is evident in these genetic syndromes. Understanding the relationship between autism, anxiety and IU is essential to informing the theoretical frameworks of anxiety in rare genetic syndromes and improving clinical interventions. Method: Sixty participants with CdLS or FXS participated in a questionnaire‐based study to examine the association between autistic characteristics, anxiety and IU. Results: IU mediated the association between autism and anxiety in participants with CdLS but not in participants with FXS. Conclusions: These results suggest that other factors may contribute to the autism‐anxiety relationship in FXS, and highlight the merit of syndrome‐specific approaches to the study of anxiety. Recommendations are made for intervention‐based research to ameliorate anxiety in CdLS.

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Contrasting Relationships Between Anxiety and Intolerance of Uncertainty in Cornelia de Lange and Fragile X Syndromes

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