Parkinsonism, dysautonomia, and intranuclear inclusions in a fragile X carrier: a clinical-pathological study

Mov Disord. 2006 Mar;21(3):420-5. doi: 10.1002/mds.20753.


A new tremor-ataxia syndrome, fragile X-associated tremor/ataxia syndrome (FXTAS), has been described among carriers of premutation expansions (55-200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. The prevalence of FMR1 premutation alleles has been reported to be 1 in 813 among men. Patients with FXTAS may also have features of parkinsonism. Postmortem findings have been described in eight patients with FXTAS and detailed descriptions of the pathological features of this syndrome have been published in two of these. We present a detailed description of the postmortem findings in a third patient. The patient had parkinsonism and was a carrier of a premutation expansion in the FMR1 gene. As in previous reports, the most prominent finding was the presence of eosinophilic nuclear inclusions in neurons and astrocytes, loss of Purkinje cells, and regional vacuolation of the cerebral white matter. As in one previous report, nuclear inclusions were also present in ependymal and choroid plexus cells. A new finding is that of nuclear inclusions in both the adeno- and neurohypophysis. These findings confirm the diffuse nature of this pathology. Further studies of clinical-pathological correlation in a larger sample of brains would provide additional insight into the mechanisms of the tremor, ataxia, and parkinsonism in these patients.

Publication types

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

MeSH terms

  • Aged
  • Autonomic Nervous System Diseases / diagnosis*
  • Autonomic Nervous System Diseases / metabolism*
  • Brain Stem / metabolism
  • Brain Stem / pathology
  • Cerebellum / metabolism
  • Cerebellum / pathology
  • Cerebral Cortex / metabolism
  • Cerebral Cortex / pathology
  • Fatal Outcome
  • Fragile X Mental Retardation Protein / genetics
  • Fragile X Syndrome / diagnosis*
  • Fragile X Syndrome / genetics
  • Fragile X Syndrome / metabolism*
  • Humans
  • Intranuclear Inclusion Bodies / metabolism*
  • Male
  • Parkinsonian Disorders / diagnosis*
  • Parkinsonian Disorders / metabolism*
  • Pituitary Gland / metabolism
  • Pituitary Gland / pathology


  • FMR1 protein, human
  • Fragile X Mental Retardation Protein