White matter tract alterations in fragile X syndrome: preliminary evidence from diffusion tensor imaging

Am J Med Genet B Neuropsychiatr Genet. 2003 Apr 1;118B(1):81-8. doi: 10.1002/ajmg.b.10035.


Fragile X syndrome, the most common form of hereditary mental retardation, causes disruption in the development of dendrites and synapses, the targets for axonal growth in the central nervous system. This disruption could potentially affect the development, wiring, and targeting of axons. The current study utilized diffusion tensor imaging (DTI) to investigate whether white matter tract integrity and connectivity are altered in fragile X syndrome. Ten females with a diagnosis of fragile X syndrome and ten, age matched, female control subjects underwent diffusion weighted MRI scans. A whole brain analysis of fractional anisotropy (FA) values was performed using statistical parametric mapping (SPM). A follow-up, regions-of-interest analysis also was conducted. Relative to controls, females with fragile X exhibited lower FA values in white matter in fronto-striatal pathways, as well as in parietal sensory-motor tracts. This preliminary study suggests that regionally specific alterations of white matter integrity occur in females with fragile X. Aberrant white matter connectivity in these regions is consistent with the profile of cognitive and behavioral features of fragile X syndrome, and potentially provide additional insight into the detrimental effects of suboptimal levels of FMRP in the developing brain.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adolescent
  • Adult
  • Brain / pathology*
  • Diffusion Magnetic Resonance Imaging / methods
  • Female
  • Fragile X Syndrome / genetics
  • Fragile X Syndrome / pathology*
  • Fragile X Syndrome / psychology
  • Humans
  • Intelligence
  • Wechsler Scales