Abstract:
Fragile X syndrome (FXS) is caused by an expanded trinucleotide repeat in the fragile X mental retardation gene (FMR1). Premutation alleles (55-200 CGG repeats) of FMR1 are known to contribute to the fragile X phenotype through genetic instability and transmission of full mutation alleles (>200 repeats) to offspring. There is now mounting evidence that the premutation alleles themselves contribute to clinical involvement, including premature ovarian failure among females and a more recently discovered fragile X-associated tremor/ataxia syndrome (FXTAS) among older males. Although classic FXTAS is rarer in female carriers than male carriers, females commonly reported muscle pain, weakness, and numbness. The aim of this study was to document the prevalence of these neurological symptoms compared to controls. DESIGN: A retrospective study was conducted of premutation females and female controls over a period of 42 months. Data were obtained by reviewing medical charts and documenting self reported neuralgias and symptoms found on neurological exam. RESULTS: Medical charts were reviewed for 105 premutation females and 55 control females. The premutation females reported symptoms of sleep disturbance, muscle pain, numbness, tremor, and diagnoses of fibromyalgia and multiple sclerosis more often than control females. Premutation females also showed sensation deficits on neurological exam more often than controls. Ataxia on exam was equal between the two groups. CONCLUSION: There is increased neuralgia reported in female carriers of the premutation FMR1 gene. A better understanding of this may give some indication of the molecular involvement in the carrier status and the function of the FMR1 gene.
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