Objective:

Background:

FXTAS is a progressive neurodegenerative disease caused by a CGG repeat in the FMR1 gene, with characteristic imaging abnormalities. Neuropathological studies have shown enlarged perivascular spaces in the basal ganglia, high levels of white matter disease, and white matter specific astrocyte degeneration. Isolated cases report strokes in FXTAS patients. CSF proteomics in FXTAS show increased lipoproteins, but there has been no systemic investigation of stroke in FXTAS.  

Design/Methods:

Consecutive retrospective FXTAS cases seen in the FXTAS Program at Rush University were collected from June 2024-September 2025. Cases had to meet diagnostic criteria for FXTAS, including imaging criteria, and have cholesterol laboratory studies available in their medical record. Demographics, stroke risk factors, and imaging findings were reported and descriptive statistics used to report the results. 

Results:

Twenty-five FXTAS cases were included (48% women, age 70.5±8.9 yrs).  Mean FMR1 CGG repeat size was 84.4±15.2. 52% of the cases were overweight (BMI>25) and 32% were obese (BMI>30). Disease duration was 7.7±5.5 yrs with average FXTAS RS score of 30.1±14.6, with FXTAS Stage 2 (n=11), Stage 3 (n=7) , Stage 4 (n=6) and 1 at Stage 5.  48% of the patients had hypercholesterolemia by history or elevated total cholesterol (>202) on laboratory studies and 64% were on cholesterol medications. Stroke was seen on brain MRI in 36% of the FXTAS patients and white matter disease in 88%.

Conclusions:

In this population of mild to moderate FXTAS patients, there is an elevated rate of hypercholesterolemia and stroke compared to the general US population rates in this age range. This is likely secondary to underlying vascular pathology and potentially cholesterol and lipoprotein abnormalities that are more common in FMR1 expansion carriers. Additional studies to better define the mechanism are needed, in addition to clinicians providing preventative care.