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

CAS School of Social Sciences & Humanities

University of Warwick
University of Birmingham
Birmingham Community Healthcare NHS Foundation Trust
University of Leicester
University of Surrey
Newcastle University
Aston University

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	Published - Dec 2025

Bibliographical note

© 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. CC BY

Funding

Funding: This work was supported by the Baily Thomas Charitable Fund, Cerebra and the Cornelia de Lange Syndrome Foundation UK and Ireland. The authors would like to thank all the participants and their families. The authors are also grateful to the Cornelia de Lange Foundation UK and Ireland and the Fragile X Society for their assistance with recruitment. The authors would also like to thank Louise Bradley, Kira Moss and Andrea Thomas for their assistance with data collection. Kayla Smith and Hayley Crawford are affiliated to the National Institute for Health and Care Research (NIHR) Applied Research Collaboration (ARC) West Midlands. The views expressed are those of the authors and not necessarily those of the NIHR or the Department of Health and Social Care.

Funders
Baily Thomas Charitable Fund, The
Cornelia de Lange Syndrome Foundation
National Institute for Health and Care Research
Cornelia de Lange Syndrome Foundation
Applied Research Collaboration (ARC) West Midlands

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

Knight2025VoRFinal published version, 910 KBLicence: CC BY

Cite this

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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.",

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AU - Groves, Laura

AU - Moss, Joanna

AU - Oliver, Chris

AU - Knight, Eve

AU - Patterson, Tom

AU - Rodgers, Jacqui

AU - Waite, Jane

AU - Crawford, Hayley

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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

Abstract

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Keywords

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