Learning objectives
Presentation of neuroimaging findings in FXTAS.
Familiarize radiologists with the main radiological signs of FXTAS so that, although it is a rare disease, it is taken into account as differential diagnosis in neurodegeneration.
Background
What is FXTAS and the FMR1 gene?
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder first described in 2001 by Hagerman et al. observed in premutation carriers of the FMR1 gene [1]. FMR1 stands for Fragile X Messenger Ribonucleoprotein 1, which replaced the former name, Fragile X Mental Retardation 1 gene, in 2022 [2]. The FMR1 gene contains a CGG repeat in the promotor region that is up to 45 CGGs long in the normal population. Carriers of the premutation allele have between 55...
Findings and procedure details
Loss of microstructural integrity and connectivity in the white matter, appearance of white matter hyperintensities (WMHs), morphological changes, and functional brain activity disturbances have been described in the brain imaging of premutation carriers with FXTAS.
WMHs
WMHs serve as the major radiological hallmarks of FXTAS: Bilateral hyperintensities of the middle cerebellar peduncles (MCP sign) on T2-weighted and FLAIR MRI are found in 52-83% of men and 0-13% of women with FXTAS. Hyperintensity in the splenium of the corpus callosum (CCS sign) has also been described...
Conclusion
Brain atrophy, cerebral and cerebellar white matter lesions and, particularly, the MCP and CCS signs in a patient with intention tremor and/or gait ataxia should suggest the diagnosis of FXTAS.
Being familiar with FXTAS imaging in the radiology community is of utmost importance for the diagnosis and subsequent FMR1 DNA testing for FXTAS and subsequent genetic counseling for the family.
Personal information and conflict of interest
L. T. Semeniuk:
Nothing to disclose
J. Y. Wang:
Nothing to disclose
A. Elias:
Nothing to disclose
F. Tassone:
Other: funding from Zynerba and the Azrieli Foundation to carry out molecular studies in fragile X syndrome. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
D. Hessl:
Other: Provides consultation to Healx and Tetra Pharmaceutical companies regarding assessment and treatment of fragile X syndrome. He is...
References
Hagerman, R., & Hagerman, P. (2021). Fragile X-associated tremor/ataxia syndrome: pathophysiology and management.Current opinion in neurology,34(4), 541–546. https://doi.org/10.1097/WCO.0000000000000954
Herring, J., Johnson, K., & Richstein, J. (2022). The Use of "Retardation" in FRAXA, FMRP, FMR1 and Other Designations.Cells,11(6), 1044. https://doi.org/10.3390/cells11061044
Randi J, Hagerman and Paul J, Hagerman. (2020). Fragile X Syndrome and Premutation Disorders: New Developments and Treatments. Mac Keith Press.
Brunberg, J. A., Jacquemont, S., Hagerman, R. J., Berry-Kravis, E. M., Grigsby, J., Leehey, M. A., Tassone, F., Brown, W. T., Greco, C. M., &...