Neuropathic features in fragile X premutation carriers

Am J Med Genet A. 2007 Jan 1;143A(1):19-26. doi: 10.1002/ajmg.a.31559.


Fragile X-associated tremor/ataxia syndrome (FXTAS) is a progressive neurological condition occurring in fragile X premutation carriers, predominantly males, and resulting in CNS dysfunction including tremor, ataxia, Parkinsonism, and cognitive decline. Neuropathic signs have also been described. The objective of this study was to compare neuropathic signs in fragile X premutation carriers versus controls and determine the relationship of these signs to CGG repeat length and tremor/ataxia. A neuropathy scale was utilized to compare distal tendon reflexes and vibration sense in subjects from a large cohort of carriers and controls undergoing neurological exam and structured videotaping sessions for movement disorder rating. The male carrier group displayed more impairment on total neuropathy, vibration and reflex scores than the corresponding control group, while female carriers were not significantly different from controls. In males, after correction for age effects, there was a correlation between CGG repeat length and both total neuropathy and reflex impairments. Age-adjusted partial correlation analyses showed an association between neuropathy scores and severity of ataxia but not tremor in carrier males and females. These data suggest that neuropathic signs are associated with the fragile X premutation, presumably occurring through the same mechanism proposed for CNS disease, namely, toxicity from expanded-CGG-repeat FMR1 mRNA.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Female
  • Fragile X Mental Retardation Protein / genetics
  • Fragile X Syndrome / diagnosis*
  • Fragile X Syndrome / genetics
  • Heterozygote
  • Humans
  • Male
  • Mass Screening
  • Peripheral Nervous System Diseases / diagnosis*
  • Peripheral Nervous System Diseases / genetics
  • Phenotype
  • Trinucleotide Repeat Expansion


  • FMR1 protein, human
  • Fragile X Mental Retardation Protein