Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2025 Oct 23.
doi: 10.1007/s10803-025-07088-0. Online ahead of print.

Relationship Between Intellectual Disability and Behavioral Comorbidity in Children With Fragile X Syndrome

Walter E Kaufmann  1 , Paul S Horn  2 , Dejan B Budimirovic  3 , Holly K Harris  4 , Reymundo Lozano  5 ; FORWARD Consortium
Collaborators, Affiliations

Relationship Between Intellectual Disability and Behavioral Comorbidity in Children With Fragile X Syndrome

Walter E Kaufmann et al. J Autism Dev Disord. .

Abstract

Purpose: Fragile X syndrome (FXS) presents with variable cognitive and neurobehavioral abnormalities. We recently reported clinically relevant behavioral subtypes in children with FXS based on a latent class analysis (LCA), which suggested an association between level of intellectual disability (ID) and frequency of co-occurring behavioral conditions. The present study further investigated ID-behavioral comorbidity associations in the same subject sample.

Methods: We analyzed the large (1,072 males, 338 females) pediatric FORWARD clinic-based natural history study database, using multiple statistical techniques including chi-square analyses, polyserial correlations, regression analyses, and LCA.

Results: We demonstrated that frequency of irritability/agitation, aggression, and self-injury (IAAS), autism spectrum disorder (ASD), hypersensitivity and, to lesser extent, perseverative behavior (OCD-like) are a function of ID level across the range of FXS clinical severity. With exception of IAAS, these associations were further supported by correlations between ID levels and scales shown to represent the aforementioned behavioral comorbidities.

Conclusion: The ID-behavioral comorbidity associations reported here could help in the identification and management of problematic behaviors in individuals with FXS and other ID-associated disorders.

Keywords: Autism symptomatology; Fragile x syndrome; Intellectual disability; Maladaptive behavior; Subtypes.

PubMed Disclaimer

Conflict of interest statement

Declarations. Competing interests: WEK is a consultant for Anavex Life Sciences, Shionogi, Quince Therapeutics, Acadia Pharmaceuticals, and Taysha Gene Therapies. DBB has been principal investigator on clinical trials funded by Ovid Therapeutics and Zynerba Pharmaceuticals; he has also consulted for Ovid Therapeutics. HKH is a co-investigator on clinical trials funded by Ionis Pharmaceuticals, Neuren Pharmaceuticals and Clinical Research Associates, LLC. The other co-author declares no competing interests.

References

    1. Ageranioti-Bélanger, S., Brunet, S., D’Anjou, G., Tellier, G., Boivin, J., & Gauthier, M. (2012). Behaviour disorders in children with an intellectual disability. Paediatrics & Child Health, 17(2), 848–848. https://doi.org/10.1093/pch/17.2.84 - DOI
    1. American Psychiatric Association. (2022). Diagnostic and statistical manual of mental Disorders – Fifth Edition, text revision (DSM-5-TR). American Psychiatric Association Publishing.
    1. Berry-Kravis, E. M., Lindemann, L., Jønch, A. E., Apostol, G., Bear, M. F., Carpenter, R. L., Crawley, J. N., Curie, A., Portes, D., Hossain, V., Gasparini, F., Gomez-Mancilla, F., Hessl, B., Loth, D., Scharf, E., Wang, S. H., Von Raison, P. P., Hagerman, F., Spooren, R., W., & Jacquemont, S. (2018). Drug development for neurodevelopmental disorders: Lessons learned from fragile X syndrome. Nature Reviews Drug Discovery, 17(4), 280–299. https://doi.org/10.1038/nrd.2017.221 - DOI - PubMed
    1. Berry-Kravis, E., Filipink, R. A., Frye, R. E., Golla, S., Morris, S. M., Andrews, H., Choo, T. H., Kaufmann, W. E., FORWARD Consortium. (2021). Seizures in fragile X syndrome: Associations and longitudinal analysis of a large clinic-based cohort. Frontiers in Pediatrics, 9, 736255. https://doi.org/10.3389/fped.2021.736255 - DOI - PubMed - PMC
    1. Boyle, L., & Kaufmann (2010). W. E. (Ed.), The behavioral phenotype of FMR1 mutations. American Journal of Medical Genetics Part C Seminars in Medical Genetics 154 C 4 469–476 https://doi.org/10.1002/ajmg.c.30277 . - DOI - PubMed

LinkOut - more resources