title: Fragile X-associated tremor/ataxia syndrome: phenotypic comparisons with other movement disorders.
abstract: OBJECTIVE
  The purpose of this paper is to review the typical cognitive and motor impairments seen in fragile X-associated tremor/ataxia syndrome (FXTAS), essential tremor (ET), Parkinson disease (PD), spinocerebellar ataxias (SCAs), multiple system atrophy (MSA), and progressive supranuclear palsy (PSP) in order to enhance diagnosis of FXTAS patients.
  
  
  METHODS
  We compared the cognitive and motor phenotypes of FXTAS with each of these other movement disorders. Relevant neuropathological and neuroimaging findings are also reviewed. Finally, we describe the differences in age of onset, disease severity, progression rates, and average lifespan in FXTAS compared to ET, PD, SCAs, MSA, and PSP. We conclude with a flow chart algorithm to guide the clinician in the differential diagnosis of FXTAS.
  
  
  RESULTS
  By comparing the cognitive and motor phenotypes of FXTAS with the phenotypes of ET, PD, SCAs, MSA, and PSP we have clarified potential symptom overlap while elucidating factors that make these disorders unique from one another. In summary, the clinician should consider a FXTAS diagnosis and testing for the Fragile X mental retardation 1 (FMR1) gene premutation if a patient over the age of 50 (1) presents with cerebellar ataxia and/or intention tremor with mild parkinsonism, (2) has the middle cerebellar peduncle (MCP) sign, global cerebellar and cerebral atrophy, and/or subcortical white matter lesions on MRI, or (3) has a family history of fragile X related disorders, intellectual disability, autism, premature ovarian failure and has neurological signs consistent with FXTAS. Peripheral neuropathy, executive function deficits, anxiety, or depression are supportive of the diagnosis.
  
  
  CONCLUSIONS
  Distinct profiles in the cognitive and motor domains between these movement disorders may guide practitioners in the differential diagnosis process and ultimately lead to better medical management of FXTAS patients.
authors.affiliation: a Department of Anatomy and Cell Biology , Rush University , Chicago , IL , USA.
authors.forename: Erin E
authors.initials: EE
authors.lastname: Robertson
authors.affiliation: b Department of Neurological Sciences , Rush University , Chicago , IL , USA.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Hall
authors.affiliation: a Department of Anatomy and Cell Biology , Rush University , Chicago , IL , USA.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: McAsey
authors.affiliation: a Department of Anatomy and Cell Biology , Rush University , Chicago , IL , USA.|b Department of Neurological Sciences , Rush University , Chicago , IL , USA.
authors.forename: Joan A
authors.initials: JA
authors.lastname: O'Keefe
mesh_terms: D000368:Aged; D001259:Ataxia / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D018450:Disease Progression; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D006801:Humans; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009069:Movement Disorders / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology; D059906:Neuroimaging; D009483:Neuropsychological Tests; D010300:Parkinson Disease / Q000175:diagnosis / Q000235:genetics / Q000503:physiopathology; D010641:Phenotype; D014202:Tremor / Q000175:diagnosis* / Q000235:genetics* / Q000503:physiopathology
chemical_list: D051860:Fragile X Messenger Ribonucleoprotein 1
keywords: FXTAS; Parkinson disease; essential tremor; multiple system atrophy; progressive supranuclear palsy; spinocerebellar ataxia