Objective:

Background:

Fragile-X-associated tremor/ataxia syndrome (FXTAS) is caused by expanded trinucleotide (CGG) repeats between 55-199 (premutation) in the Fragile X Mental Retardation 1 (FMR1) gene. Core clinical features of FXTAS include cerebellar ataxia, intention tremor and Parkinsonism. In contrast, a full mutation of CGG repeats>200 repeats with methylation of the gene leads to fragile X syndrome, which is characterized by early intellectual disability, autistic features, and seizures. FMR1 premutation carrier women presenting as FXTAS have been reported. This is the first report of a woman with a full mutation presenting with FXTAS. 

Design/Methods:

N/A

Results:

A 65-year-old woman presented with problems with dexterity and shuffling gait. The patient also complained of urinary urgency, constipation, anxiety, depression, and mild cognitive complaints. The patient’s son was diagnosed with fragile X syndrome at 14 months. Neurological exam of the patient showed parkinsonism, action tremor and limb ataxia. MRI brain demonstrated chronic ischemic small vessel disease and mildly reduced brain volume. FMR1 CGG repeat sizes were 20 and >200. The 20 repeat allele was seen on the active X chromosome (representing non-random X-inactivation), while the >200 repeat allele was fully methylated on Southern blot. Testing for Parkinson’s disease-associated genes were negative. 

Conclusions:

This is the first report of a woman with a FMR1 full mutation presenting with signs and symptoms of FXTAS. Several cases of FXTAS have been reported in FMR1 full mutation men with fragile X syndrome due to mosaicism of repeat sizes and the presence of a premutation allele. Full mutation adults with complete methylation have not been reported to have FXTAS. The clinical presentation of this case might be due to size or methylation mosaicism in brain. Alternatively, one could also consider a different disease mimicking FXTAS.