Document Detail


Fragile X-associated tremor/ataxia syndrome: clinical features, genetics, and testing guidelines.
MedLine Citation:
PMID:  17618523     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fragile X-associated tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder with core features of action tremor and cerebellar gait ataxia. Frequent associated findings include parkinsonism, executive function deficits and dementia, neuropathy, and dysautonomia. Magnetic Resonance Imaging studies in FXTAS demonstrate increased T2 signal intensity in the middle cerebellar peduncles (MCP sign) in the majority of patients. Similar signal alterations are seen in deep and subependymal cerebral white matter, as is general cortical and subcortical atrophy. The major neuropathological feature of FXTAS is the presence of intranuclear, neuronal, and astrocytic, inclusions in broad distribution throughout the brain and brainstem. FXTAS is caused by moderate expansions (55-200 repeats; premutation range) of a CGG trinucleotide in the fragile X mental retardation 1 (FMR1) gene, the same gene which causes fragile X syndrome when in the full mutation range (200 or greater CGG repeats). The pathogenic mechanism is related to overexpression and toxicity of the FMR1 mRNA per se. Although only recently discovered, and hence currently under-diagnosed, FXTAS is likely to be one of the most common single-gene disorders leading to neurodegeneration in males. In this report, we review information available on the clinical, radiological, and pathological features, and prevalence and management of FXTAS. We also provide guidelines for the practitioner to assist with identifying appropriate patients for DNA testing for FXTAS, as well as recommendations for genetic counseling once a diagnosis of FXTAS is made.
Authors:
Elizabeth Berry-Kravis; Liane Abrams; Sarah M Coffey; Deborah A Hall; Claudia Greco; Louise W Gane; Jim Grigsby; James A Bourgeois; Brenda Finucane; Sebastien Jacquemont; James A Brunberg; Lin Zhang; Janet Lin; Flora Tassone; Paul J Hagerman; Randi J Hagerman; Maureen A Leehey
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Publication Detail:
Type:  Journal Article; Review    
Journal Detail:
Title:  Movement disorders : official journal of the Movement Disorder Society     Volume:  22     ISSN:  0885-3185     ISO Abbreviation:  Mov. Disord.     Publication Date:  2007 Oct 
Date Detail:
Created Date:  2007-11-05     Completed Date:  2008-02-01     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  8610688     Medline TA:  Mov Disord     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2018-30, quiz 2140     Citation Subset:  IM    
Copyright Information:
(c) 2007 Movement Disorder Society.
Affiliation:
Department of Pediatrics, Rush University Medical Center, Chicago, Illinois 60612, USA. Elizabeth_m_berry-kravis@rush.edu
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MeSH Terms
Descriptor/Qualifier:
Ataxia / genetics*,  pathology,  physiopathology
Family Health
Female
Fragile X Syndrome / genetics*,  pathology,  physiopathology
Genetic Testing
Guidelines as Topic / standards*
Humans
Magnetic Resonance Imaging / methods
Male
Sex Factors
Tremor / genetics*,  pathology,  physiopathology

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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