FXTAS
MCID: FRG010
MIFTS: 43

Fragile X Tremor/ataxia Syndrome (FXTAS)

Categories: Genetic diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Fragile X Tremor/ataxia Syndrome

MalaCards integrated aliases for Fragile X Tremor/ataxia Syndrome:

Name: Fragile X Tremor/ataxia Syndrome 58 76 38 30 13 6 41 74
Fxtas 58 76
Fragile X-Associated Tremor/ataxia Syndrome 60
Fxtas Syndrome 60

Characteristics:

Orphanet epidemiological data:

60
fragile x-associated tremor/ataxia syndrome
Inheritance: X-linked dominant; Prevalence: 1-9/100000 (United States); Age of onset: Adult; Age of death: elderly;

OMIM:

58
Inheritance:
x-linked dominant

Miscellaneous:
onset in fifties or sixties
caused by 55-200 expanded trinucleotide repeats in the fmr1 gene referred to as a 'premutation'
most patients have a family history of fragile x syndrome
full mutations with expanded trinucleotide repeats greater than 200 result in fragile x mental retardation syndrome
males are more commonly affected than females


HPO:

33
fragile x tremor/ataxia syndrome:
Onset and clinical course adult onset
Inheritance x-linked dominant inheritance


Classifications:

Orphanet: 60  
Rare neurological diseases


Summaries for Fragile X Tremor/ataxia Syndrome

OMIM : 58 Jacquemont et al. (2007) provided a review of fragile X syndrome, which they characterized as a neurodevelopmental disorder, and FXTAS, which they characterized as a neurodegenerative disorder. Amiri et al. (2008) provided a review of FXTAS and noted that the pathogenesis of the disorder is distinct from that in fragile X syndrome. FXTAS results form a toxic gain of function of FMR1 RNA, whereas fragile X syndrome results from a loss of FMR1 function. The penetrance of FXTAS in male carriers aged 50 years and over, ascertained through families with a fragile X syndrome proband, is at least 33% (Hagerman and Hagerman, 2004); its penetrance in female carriers is approximately 5-10% (Greco et al., 2008). (300623)

MalaCards based summary : Fragile X Tremor/ataxia Syndrome, also known as fxtas, is related to fragile x-associated tremor/ataxia syndrome and tremor, and has symptoms including ataxia, tremor and gait ataxia. An important gene associated with Fragile X Tremor/ataxia Syndrome is FMR1 (Fragile X Mental Retardation 1), and among its related pathways/superpathways is RNA transport. The drugs Progesterone and Pregnanolone have been mentioned in the context of this disorder. Affiliated tissues include brain, testes and eye, and related phenotypes are depressivity and hypothyroidism

UniProtKB/Swiss-Prot : 76 Fragile X tremor/ataxia syndrome: In FXTAS, the expanded repeats range in size from 55 to 200 repeats and are referred to as 'premutations'. Full repeat expansions with greater than 200 repeats results in fragile X mental retardation syndrome [MIM:300624]. Carriers of the premutation typically do not show the full fragile X syndrome phenotype, but comprise a subgroup that may have some physical features of fragile X syndrome or mild cognitive and emotional problems.

Related Diseases for Fragile X Tremor/ataxia Syndrome

Graphical network of the top 20 diseases related to Fragile X Tremor/ataxia Syndrome:



Diseases related to Fragile X Tremor/ataxia Syndrome

Symptoms & Phenotypes for Fragile X Tremor/ataxia Syndrome

Human phenotypes related to Fragile X Tremor/ataxia Syndrome:

60 33 (show all 48)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 depressivity 60 33 Frequent (79-30%) HP:0000716
2 hypothyroidism 60 33 Occasional (29-5%) HP:0000821
3 dysarthria 60 33 Very frequent (99-80%) HP:0001260
4 bowel incontinence 60 33 Occasional (29-5%) HP:0002607
5 anxiety 60 33 Frequent (79-30%) HP:0000739
6 gait ataxia 60 33 Very frequent (99-80%) HP:0002066
7 dysmetria 60 33 Very frequent (99-80%) HP:0001310
8 intention tremor 60 33 Very frequent (99-80%) HP:0002080
9 memory impairment 60 33 Very frequent (99-80%) HP:0002354
10 myalgia 60 33 Occasional (29-5%) HP:0003326
11 dementia 60 33 Very frequent (99-80%) HP:0000726
12 hyporeflexia 60 33 Frequent (79-30%) HP:0001265
13 bradykinesia 60 33 Occasional (29-5%) HP:0002067
14 impotence 60 33 Frequent (79-30%) HP:0000802
15 parkinsonism 60 33 Occasional (29-5%) HP:0001300
16 nystagmus 33 HP:0000639
17 hypertension 60 Occasional (29-5%)
18 ataxia 60 Very frequent (99-80%)
19 gait disturbance 60 Very frequent (99-80%)
20 muscle weakness 60 Frequent (79-30%)
21 dysphagia 60 Occasional (29-5%)
22 dysautonomia 60 Frequent (79-30%)
23 hypotension 60 Occasional (29-5%)
24 hearing impairment 33 HP:0000365
25 peripheral neuropathy 60 Frequent (79-30%)
26 premature ovarian insufficiency 33 HP:0008209
27 urinary bladder sphincter dysfunction 60 Frequent (79-30%)
28 poor fine motor coordination 33 HP:0007010
29 mask-like facies 33 HP:0000298
30 cerebral cortical atrophy 60 Very frequent (99-80%)
31 rigidity 60 Frequent (79-30%)
32 obsessive-compulsive behavior 60 Frequent (79-30%)
33 dysdiadochokinesis 33 HP:0002075
34 saccadic smooth pursuit 33 HP:0001152
35 postural tremor 33 HP:0002174
36 cerebellar atrophy 33 HP:0001272
37 urinary incontinence 33 HP:0000020
38 pollakisuria 60 Frequent (79-30%)
39 abnormality of brainstem morphology 60 Occasional (29-5%)
40 disinhibition 33 HP:0000734
41 obsessive-compulsive trait 33 HP:0008770
42 diffuse cerebellar atrophy 60 Frequent (79-30%)
43 resting tremor 33 HP:0002322
44 dysesthesia 60 Frequent (79-30%)
45 diffuse cerebral atrophy 33 HP:0002506
46 inertia 60 Very frequent (99-80%)
47 impaired distal vibration sensation 33 HP:0006886
48 impaired tandem gait 33 HP:0031629

Symptoms via clinical synopsis from OMIM:

58
Head And Neck Eyes:
nystagmus
saccadic pursuit

Neurologic Central Nervous System:
dysarthria
dysmetria
intention tremor
dysdiadochokinesis
action tremor
more
Neurologic Behavioral Psychiatric Manifestations:
anxiety
disinhibition
depression
executive dysfunction
obsessive-compulsive disorder

Genitourinary External Genitalia Male:
impotence

Genitourinary Internal Genitalia Female:
premature ovarian failure

Muscle Soft Tissue:
muscle pain
fibromyalgia

Laboratory Abnormalities:
increased intracellular fmrp mrna
decreased intracellular fmr protein

Endocrine Features:
hypothyroidism
premature ovarian failure

Neurologic Peripheral Nervous System:
peripheral neuropathy
hyporeflexia
lower extremity numbness
decreased distal vibratory sensation
lower extremity paresthesias

Genitourinary Bladder:
urinary incontinence

Head And Neck Ears:
hearing loss

Abdomen Gastrointestinal:
incontinence

Head And Neck Face:
masked facies

Clinical features from OMIM:

300623

UMLS symptoms related to Fragile X Tremor/ataxia Syndrome:


ataxia, tremor, gait ataxia, myalgia, dysdiadochokinesis, action tremor, bradykinesia, resting tremor, paresthesia lower limb, static tremor, lower extremity numbness

Drugs & Therapeutics for Fragile X Tremor/ataxia Syndrome

Drugs for Fragile X Tremor/ataxia Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 12)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Progesterone Approved, Vet_approved Phase 2 57-83-0 5994
2 Pregnanolone Phase 2 128-20-1
3 Central Nervous System Depressants Phase 2
4 Pharmaceutical Solutions Phase 2
5 Anesthetics Phase 2
6
Dopamine Approved Not Applicable 62-31-7, 51-61-6 681
7
Memantine Approved, Investigational Not Applicable 19982-08-2 4054
8 Excitatory Amino Acids Not Applicable
9 Excitatory Amino Acid Antagonists Not Applicable
10 Neurotransmitter Agents Not Applicable
11 Dopamine Agents Not Applicable
12 Antiparkinson Agents Not Applicable

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Treatment of Fragile-X Associated Tremor/Ataxia Syndrome (FXTAS) With Allopregnanolone Completed NCT02603926 Phase 2 Allopregnanolone
2 Citocoline for Treatment of FXTAS Completed NCT02197104 Phase 2 citocoline
3 Memantine Treatment in Fragile X-Associated Tremor/Ataxia Syndrome Completed NCT00584948 Not Applicable Memantine;Placebo
4 Genetic Characterization of Movement Disorders and Dementias Recruiting NCT02014246
5 Rare Disease Patient Registry & Natural History Study - Coordination of Rare Diseases at Sanford Recruiting NCT01793168

Search NIH Clinical Center for Fragile X Tremor/ataxia Syndrome

Genetic Tests for Fragile X Tremor/ataxia Syndrome

Genetic tests related to Fragile X Tremor/ataxia Syndrome:

# Genetic test Affiliating Genes
1 Fragile X Tremor/ataxia Syndrome 30 FMR1

Anatomical Context for Fragile X Tremor/ataxia Syndrome

MalaCards organs/tissues related to Fragile X Tremor/ataxia Syndrome:

42
Brain, Testes, Eye

Publications for Fragile X Tremor/ataxia Syndrome

Articles related to Fragile X Tremor/ataxia Syndrome:

(show top 50) (show all 133)
# Title Authors Year
1
The FMRpolyGlycine Protein Mediates Aggregate Formation and Toxicity Independent of the CGG mRNA Hairpin in a Cellular Model for FXTAS. ( 30984240 )
2019
2
FXTAS: regional decrease of mitochondrial DNA copy number relates to clinical manifestations. ( 30887649 )
2019
3
Astroglial-targeted expression of the fragile X CGG repeat premutation in mice yields RAN translation, motor deficits and possible evidence for cell-to-cell propagation of FXTAS pathology. ( 30808398 )
2019
4
Low diagnostic accuracy of fragile X tremor/ataxia syndrome diagnostic criteria in late onset ataxia. ( 30735585 )
2019
5
FMRpolyG alters mitochondrial transcripts level and respiratory chain complex assembly in Fragile X associated tremor/ataxia syndrome [FXTAS]. ( 30771487 )
2019
6
Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). ( 30900185 )
2019
7
Fentanyl overdose in a female with the FMR1 premutation and FXTAS. ( 31032490 )
2018
8
Microglial cell activation and senescence are characteristic of the pathology FXTAS. ( 30537011 )
2018
9
Cognitive Deficits and Associated ERP N400 Abnormalities in FXTAS With Parkinsonism. ( 30279697 )
2018
10
Assessment of Molecular Measures in Non-FXTAS Male Premutation Carriers. ( 30186307 )
2018
11
Middle Cerebellar Peduncle Width-A Novel MRI Biomarker for FXTAS? ( 29988561 )
2018
12
Acute Stroke in Middle Cerebellar Peduncle in a Patient With FXTAS. ( 29887875 )
2018
13
Frequency of SCA8, SCA10, SCA12, SCA36, FXTAS and C9orf72 repeat expansions in SCA patients negative for the most common SCA subtypes. ( 29316893 )
2018
14
Making a Difference-Positive Effect of Unilateral VIM Gamma Knife Thalamotomy in the Therapy of Tremor in Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). ( 29997574 )
2018
15
Potential pathogenic mechanisms underlying Fragile X Tremor Ataxia Syndrome: RAN translation and/or RNA gain-of-function? ( 29223504 )
2018
16
Repeat-associated non-AUG (RAN) translation and other molecular mechanisms in Fragile X Tremor Ataxia Syndrome. ( 29453961 )
2018
17
Impaired Mitochondrial Function and Dynamics in the Pathogenesis of FXTAS. ( 27771901 )
2017
18
Concomitant occurrence of FXTAS and clinically defined sporadic inclusion body myositis: report of two cases. ( 28857524 )
2017
19
Translation of Expanded CGG Repeats into FMRpolyG Is Pathogenic and May Contribute to Fragile X Tremor Ataxia Syndrome. ( 28065649 )
2017
20
Clinically significant psychiatric symptoms among male carriers of the fragile X premutation, with and without FXTAS, and the mediating influence of executive functioning. ( 27355103 )
2016
21
Carriage of One or Two FMR1 Premutation Alleles Seems to Have No Effect on Illness Severity in a FXTAS Female with an Autozygous FMR1 Premutation Allele. ( 27315125 )
2016
22
Update on the Clinical, Radiographic, and Neurobehavioral Manifestations in FXTAS and FMR1 Premutation Carriers. ( 27287737 )
2016
23
Cerebellar Mild Iron Accumulation in a Subset of FMR1 Premutation Carriers with FXTAS. ( 27259564 )
2016
24
A Majority of FXTAS Cases Present with Intranuclear Inclusions Within Purkinje Cells. ( 27108270 )
2016
25
Repeat-associated non-AUG translation from antisense CCG repeats in fragile X tremor/ataxia syndrome. ( 27761921 )
2016
26
Altered redox mitochondrial biology in the neurodegenerative disorder fragile X-tremor/ataxia syndrome: use of antioxidants in precision medicine. ( 27385396 )
2016
27
Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS) Motor Dysfunction Modeled in Mice. ( 27255703 )
2016
28
Late Onset Tremor and Ataxia Syndrome: FXTAS and its Ignored Peripheral Nervous System Findings in Diagnostic Criteria. ( 28360777 )
2016
29
Fragile X tremor ataxia syndrome and white matter dementia. ( 27356088 )
2016
30
Reversibility of neuropathology and motor deficits in an inducible mouse model for FXTAS. ( 26060190 )
2015
31
Methadone use in a male with the FMRI premutation and FXTAS. ( 25900641 )
2015
32
Erratum: Emerging topics in FXTAS. ( 25852777 )
2015
33
Relevance of corpus callosum splenium versus middle cerebellar peduncle hyperintensity for FXTAS diagnosis in clinical practice. ( 25451852 )
2015
34
Immune mediated disorders in women with a fragile X expansion and FXTAS. ( 25399540 )
2015
35
Pearls & Oy-sters: fragile X tremor/ataxia syndrome: a diagnostic dilemma. ( 25688154 )
2015
36
EMQN best practice guidelines for the molecular genetic testing and reporting of fragile X syndrome and other fragile X-associated disorders. ( 25227148 )
2015
37
Small fiber neuropathy in a woman with fragile X-associated tremor/ataxia syndrome (FXTAS). ( 25488474 )
2015
38
Characterization and Early Detection of Balance Deficits in Fragile X Premutation Carriers With and Without Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). ( 25763861 )
2015
39
Fragile X Tremor Ataxia Syndrome With Rapidly Progressive Myopathy. ( 26258737 )
2015
40
Long-term improvement of tremor and ataxia after bilateral DBS of VoP/zona incerta in FXTAS. ( 25862802 )
2015
41
Emerging topics in FXTAS. ( 25642984 )
2014
42
FXTAS: size does matter! ( 25485575 )
2014
43
Identification of FXTAS presenting with SCA 12 like phenotype in India. ( 25085749 )
2014
44
Eye movements reveal impaired inhibitory control in adult male fragile X premutation carriers asymptomatic for FXTAS. ( 24773414 )
2014
45
EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood. ( 24418350 )
2014
46
Targeting the r(CGG) repeats that cause FXTAS with modularly assembled small molecules and oligonucleotides. ( 24506227 )
2014
47
FXTAS in an unmethylated mosaic male with fragile X syndrome from Chile. ( 24028275 )
2014
48
Parkinsonism in fragile X-associated tremor/ataxia syndrome (FXTAS): revisited. ( 24491663 )
2014
49
Memantine effects on verbal memory in fragile X-associated tremor/ataxia syndrome (FXTAS): a double-blind brain potential study. ( 24871547 )
2014
50
ERP abnormalities elicited by word repetition in fragile X-associated tremor/ataxia syndrome (FXTAS) and amnestic MCI. ( 25111034 )
2014

Variations for Fragile X Tremor/ataxia Syndrome

ClinVar genetic disease variations for Fragile X Tremor/ataxia Syndrome:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 FMR1 FMR1, (CGG)n EXPANSION NT expansion Pathogenic
2 FMR1 NM_002024.5(FMR1): c.-128_-126GGC(55_200) NT expansion Pathogenic GRCh38 Chromosome X, 147912052: 147912054
3 FMR1 NM_002024.5(FMR1): c.-128_-126GGC(55_200) NT expansion Pathogenic GRCh37 Chromosome X, 146993570: 146993572

Expression for Fragile X Tremor/ataxia Syndrome

Search GEO for disease gene expression data for Fragile X Tremor/ataxia Syndrome.

Pathways for Fragile X Tremor/ataxia Syndrome

Pathways related to Fragile X Tremor/ataxia Syndrome according to KEGG:

38
# Name Kegg Source Accession
1 RNA transport hsa03013

Pathways related to Fragile X Tremor/ataxia Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 10.84 FMR1 RAN

GO Terms for Fragile X Tremor/ataxia Syndrome

Cellular components related to Fragile X Tremor/ataxia Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 postsynapse GO:0098794 8.62 FMR1 PURA

Biological processes related to Fragile X Tremor/ataxia Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 negative regulation of translation GO:0017148 8.62 FMR1 PURA

Sources for Fragile X Tremor/ataxia Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
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45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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