Conversion disorder in women with the FMR1 premutation

Area of Science:

• Neurogenetics
• Psychiatry

Background:

• Fragile X mental retardation (FMR1) gene premutations were previously thought to not affect female carriers.
• Emerging evidence indicates significant health risks for female carriers.

Observation:

• Up to 8% of older female FMR1 premutation carriers develop fragile X-associated tremor/ataxia syndrome (FXTAS).
• Other associated conditions include primary ovarian insufficiency, thyroid disease, hypertension, seizures, peripheral neuropathy, and fibromyalgia.
• A 60-year-old woman with an FMR1 premutation presented with depression, anxiety, and conversion disorder with seizures.

Findings:

• The FMR1 premutation is associated with a range of neurological and psychiatric conditions in women.
• The study postulates FMR1 premutation mRNA toxicity as a neurobiological mechanism for conversion symptoms.

Implications:

• Highlights the importance of genetic screening for FMR1 premutations in women with unexplained neurological and psychiatric symptoms.
• Suggests potential therapeutic targets related to mRNA toxicity and neural dysconnectivity in FMR1-associated disorders.