Parkinsonism Versus Concomitant Parkinson's Disease in Fragile X–Associated Tremor/Ataxia Syndrome

María Jimena Salcedo-Arellano, Marisol Wendy Wolf-Ochoa, Tiffany Hong, Sarwat Amina, Flora Tassone, Mirna Lechpammer, Randi Hagerman, Verónica Martínez-Cerdeño

Research output: Contribution to journalArticlepeer-review

6 Scopus citations


Background: Fragile X–associated tremor/ataxia syndrome (FXTAS) is a late-onset neurodegenerative disorder associated with premutation alleles (55–200 CGG repeats) of the fragile X mental retardation 1 (FMR1) gene. FXTAS is characterized by the presence of ubiquitin-positive inclusions in neurons and astrocytes and by cerebellar tremor and ataxia. Parkinsonism has been reported in FXTAS, but most patients lack the characteristic rest tremor and severe rigidity seen in idiopathic Parkinson's disease (PD). Objective: To describe the frequency of concomitant PD in FXTAS. Methods: We reviewed the medical record of 40 deceased patients diagnosed with FXTAS and performed a pathology analysis to confirm both FXTAS and PD. Results: Clinical histories indicated that 5 FXTAS patients were diagnosed with idiopathic PD and 2 with atypical parkinsonian syndrome. After pathological examination, we found that 7 patients in the PD clinical diagnosis group had dopaminergic neuronal loss; however, only 2 of 7 presented Lewy bodies (LBs) in the substantia nigra. Therefore, a total of 5% of the 40 cohort patients met the pathologic criteria for the concomitant diagnosis of FXTAS and PD. In addition, 2 patients not clinically diagnosed with PD also had nigral neuronal loss with LBs in substantia nigra. In total 10% of these 40 patients had LBs. Conclusion: This report expands our understanding of clinical symptoms and unusual presentations in patients with FXTAS and the concept that the parkinsonism found in FXTAS is sometimes indistinguishable from PD. We propose that FMR1 should be recognized as one of the exceptional genetic causes of parkinsonism with presynaptic dopaminergic loss and LBs.

Original languageEnglish (US)
JournalMovement Disorders Clinical Practice
StateAccepted/In press - Jan 1 2020


  • fragile X associated tremor/ataxia syndrome
  • fragile X mental retardation 1 gene
  • neuropathology
  • Parkinson's disease
  • parkinsonism

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology


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