Parkinsonism in fragile X-associated tremor/ataxia syndrome (FXTAS): revisited.
BACKGROUND
Parkinsonian features have been used as a minor diagnostic criterion for fragile X-associated tremor/ataxia syndrome (FXTAS). However, prior studies have examined parkinsonism (defined as having bradykinesia with at least rest tremor or postural instability) mostly in premutation carriers without a diagnosis of FXTAS. The current study was intended to elaborate this important aspect of the FXTAS spectrum, and to quantify the relationships between parkinsonism, FXTAS clinical staging and genetic/molecular measures.


METHODS
Thirty eight (38) FXTAS patients and 10 age-matched normal controls underwent a detailed neurological examination that included all but one item (i.e. rigidity) of the motor section of the Unified Parkinson's Disease Rating Scale (UPDRS).


RESULTS
The FXTAS patient group displayed substantially higher prevalence of parkinsonian features including body bradykinesia (57%) and rest tremor (26%), compared to the control group. Furthermore, parkinsonism was identified in 29% of FXTAS patients. Across all patients, body bradykinesia scores significantly correlated with FXTAS clinical stage, FMR1 mRNA level, and ataxic gait of cerebellar origin, while postural instability was associated with intention tremor.


CONCLUSIONS
Parkinsonian features in FXTAS appear to be characterized as bradykinesia concurrent with cerebellar gait ataxia, postural instability accompanied by intention tremor, and frequent rest tremor, representing distinctive patterns that highlight the need for further clinical studies including genetic testing for the FMR1 premutation. The association between FMR1 mRNA level and bradykinesia implicates pathophysiological mechanisms which may link FMR1 mRNA toxicity, dopamine deficiency and parkinsonism in FXTAS.
Department of Neurology, University of California Davis, Sacramento, CA, USA; Center for Mind and Brain, University of California Davis, Davis, CA, USA. Electronic address: niuyq2006@gmail.com.
Yu-Qiong
YQ
Niu
Department of Neurology, University of California Davis, Sacramento, CA, USA; Center for Mind and Brain, University of California Davis, Davis, CA, USA.
Jin-Chen
JC
Yang
Department of Neurological Sciences, Rush University, Chicago, IL, USA.
Deborah A
DA
Hall
Department of Neurology, University of Colorado, Denver, CO, USA.
Maureen A
MA
Leehey
Department of Biochemistry and Molecular Medicine, University of California Davis, Davis, CA, USA; Medical Investigations of Neurodevelopmental Disorders (MIND) Institute, University of California Davis, Sacramento, CA, USA.
Flora
F
Tassone
Department of Neurology, University of California Davis, Sacramento, CA, USA; Center for Mind and Brain, University of California Davis, Davis, CA, USA.
John M
JM
Olichney
Medical Investigations of Neurodevelopmental Disorders (MIND) Institute, University of California Davis, Sacramento, CA, USA; Department of Pediatrics, University of California Davis, School of Medicine, Sacramento, CA, USA.
Randi J
RJ
Hagerman
Department of Neurology, University of California Davis, Sacramento, CA, USA. Electronic address: lin.zhang@ucdmc.ucdavis.edu.
Lin
L
Zhang
D000368:Aged; D001259:Ataxia / Q000150:complications* / Q000235:genetics; D005260:Female; D051860:Fragile X Messenger Ribonucleoprotein 1 / Q000235:genetics; D005600:Fragile X Syndrome / Q000150:complications* / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020734:Parkinsonian Disorders / Q000453:epidemiology / Q000209:etiology*; D015995:Prevalence; D012333:RNA, Messenger / Q000032:analysis; D012189:Retrospective Studies; D014202:Tremor / Q000150:complications* / Q000235:genetics; D014741:Video Recording
D051860:Fragile X Messenger Ribonucleoprotein 1; D012333:RNA, Messenger; C497683:FMR1 protein, human
Bradykinesia; FMR1 mRNA; Fragile X premutation; Parkinsonism