Background

Conducting clinical trials is essential to identify new therapies. Even though we can conduct clinical trials for several single gene neurodevelopmental disorders (disorders linked to changes in only one gene), one major issue is that each condition is relatively rare. This means that the development of therapies, treatments, or specific support for each disorder is unlikely. Yet, taken together these single gene neurodevelopmental conditions are not rare. If we could create groups of single gene disorders that are likely to respond to the same drug, developing new treatments and therapies would become more feasible, and more robust trials could be conducted.

Why did we do this study?

This project focuses on two single gene neurodevelopmental disorders: Fragile X syndrome (caused by a change in the FMR1 gene) and SYNGAP1-related intellectual disability (caused by changes in the SYNGAP1 gene). We want to describe how genetic changes shape people with neurodevelopmental conditions, especially regarding their clinical, behavioural, cognitive, and neurological characteristics. Our hope is that this will:

1) help us better understand people with neurodevelopmental conditions and genetic changes

2) improve our chances of developing new therapies

3) make it easier to do clinical trials to test new therapies

What did we do?

We measured the clinical profiles and mental abilities of a large group of people with fragile x syndrome or SYNGAP1 related intellectual disability (ID), aged 3 to 65.  We used clinical measures (a clinical interview alongside parent completed questionnaires), cognitive tests including eye tracking and EEG.

What did we find?

So far, the project has made a number of important findings in relation to SYNGAP1-related ID. We have found that those with SYNGAP1-related ID demonstrated higher levels of autistic traits, significant sleep abnormalities, fewer adaptive behaviors, along with higher levels of internalizing and externalizing behaviors compared with typically developing controls. Our eye tracking study demonstrated that, in comparison to typically developing controls, those with SYNGAP1-related ID showed different social attention looking patterns, particularly to faces. Our semi-structured interviews with the parents and caregivers of a SYNGAP1 related ID child highlighted their general behaviour affected the themes of daily living skills, distress-related behaviours, emotional regulation, difficulties with change, a lack of danger awareness, and sensory differences. Sensory features described involved auditory, visual, tactile, gustatory, and proprioceptive themes.

Outputs

The findings have been published in a peer-reviewed journal, and are available at:

Wright, D., Kenny, A., Mizen, L.A.M. et al. Profiling Autism and Attention Deficit Hyperactivity Disorder Traits in Children with SYNGAP1-Related Intellectual Disability. J Autism Dev Disord 55, 297–309 (2025). https://doi.org/10.1007/s10803-023-06162-9

Wright, D., Kenny, A., Eley, S., McKechanie, A. G., & Stanfield, A. C. (2024). Visual social attention in SYNGAP1‐related intellectual disability. Autism Research, 17(6), 1083-1093.  https://doi.org/10.1002/aur.3148

Wright, D., Kenny, A., Mizen, L. A. M., McKechanie, A. G., & Stanfield, A. C. (2024). The Behavioral Profile of SYNGAP1-Related Intellectual Disability. American Journal on Intellectual and Developmental Disabilities, 129(3), 199–214. https://doi.org/10.1352/1944-7558-129.3.199

Wright, D., Kenny, A., Eley, S. et al. Clinical and behavioural features of SYNGAP1-related intellectual disability: a parent and caregiver description. J Neurodevelop Disord 14, 34 (2022). https://doi.org/10.1186/s11689-022-09437-x

Smith-Hicks, C., Wright, D., Kenny, A., Stowe, R. C., McCormack, M., Stanfield, A. C., & Holder, J. L., Jr. (2021). Sleep Abnormalities in the Synaptopathies—SYNGAP1-Related Intellectual Disability and Phelan–McDermid Syndrome. Brain Sciences, 11(9), 1229. https://doi.org/10.3390/brainsci11091229

Who conducted and funded the project?

The project was conducted by Dr Damien Wright, Aisling Kenny, Dr Andrew McKechanie and Dr Andrew Stanfield.

This project was funded by the University of Edinburgh’s Patrick Wild Centre and Simons Initiative for the Developing Brain (SIDB) grant awarded to Dr Andrew Stanfield. Funding for SIDB is from a Simons Foundation Autism Research Initiative award. Funding was also received from the Welcome Trust (Institutional Strategic Support Fund). We would like to thank all the participants and their families who took part along with the SYNGAP1 Foundation and SynGAP Research Fund for their help with participant recruitment.