Premutation Females with preFXTAS

Area of Science:

• Neurogenetics
• Neurology
• Genetics

Background:

• Fragile-X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurodegenerative disorder linked to the FMR1 gene premutation (55-200 CGG repeats).
• FXTAS typically affects males around age 60 with motor and cognitive symptoms.
• Female FXTAS presentation and progression differ significantly from males.

Observation:

• Ten women with FMR1 premutation were studied across two medical centers.
• All participants exhibited neuropsychiatric symptoms and subtle neurological signs.
• Motor symptoms like tremors and ataxia were absent or reduced; neuropsychiatric symptoms were prevalent.

Findings:

• Women with FMR1 premutation show a distinct clinical profile compared to men.
• Neurocognitive impairment was minimal, with some executive dysfunction and memory complaints.
• The term 'preFXTAS' or 'prodromic FXTAS' is proposed for early-stage presentations in women.

Implications:

• This study highlights the need for revised diagnostic criteria for FXTAS in females.
• Development of specific biomarkers and assessment tools for women is crucial.
• Recognizing distinct female presentations can improve early diagnosis and management of FXTAS.