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FXTAS
MCID: FRG010
MIFTS: 43

Fragile X Tremor/ataxia Syndrome (FXTAS)

Categories: Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Fragile X Tremor/ataxia Syndrome

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MalaCards integrated aliases for Fragile X Tremor/ataxia Syndrome:

Name: Fragile X Tremor/ataxia Syndrome 56 73 36 29 13 6 39 71
Fxtas 56 73
Fragile X-Associated Tremor/ataxia Syndrome 58
Fxtas Syndrome 58

Characteristics:

Orphanet epidemiological data:

58
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:

56
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:

31
fragile x tremor/ataxia syndrome:
Onset and clinical course adult onset
Inheritance x-linked dominant inheritance


Classifications:

MalaCards categories:
Global: Genetic diseases Rare diseases
Anatomical: Neuronal diseases Mental diseases
See all MalaCards categories (disease lists)
ICD10: 33
Orphanet: 58  
Rare neurological diseases


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Summaries for Fragile X Tremor/ataxia Syndrome

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OMIM : 56 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 myalgia. An important gene associated with Fragile X Tremor/ataxia Syndrome is FMR1 (FMRP Translational Regulator 1), and among its related pathways/superpathways is RNA transport. The drugs Progesterone and Central Nervous System Depressants have been mentioned in the context of this disorder. Affiliated tissues include brain, testes and heart, and related phenotypes are depressivity and dysarthria

KEGG : 36 Fragile X tremor/ataxia syndrome (FXTAS) is a neurodegenerative disorder affecting carriers of premutation CGG repeat expansions (range: 55-200) in the fragile X mental retardation 1 (FMR1) gene. Common manifestations of FXTAS are progressive intention tremor, cerebellar gait ataxia, parkinsonism, working memory impairment, and frontal executive dysfunction. FXTAS occurs predominantly in men over age 50 years.

UniProtKB/Swiss-Prot : 73 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.

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Related Diseases for Fragile X Tremor/ataxia Syndrome

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Diseases related to Fragile X Tremor/ataxia Syndrome via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 80)
# Related Disease Score Top Affiliating Genes
1 fragile x-associated tremor/ataxia syndrome 32.5 LOC108684022 FMR1-AS1 FMR1
2 tremor 31.2 LOC108684022 FMR1
3 fmr1 disorders 30.3 LOC108684022 FMR1
4 learning disability 30.0 PURA FMR1
5 fragile x syndrome 29.9 LOC108684022 FMR1-AS1 FMR1
6 alacrima, achalasia, and mental retardation syndrome 29.4 PURA FMR1
7 ataxia and polyneuropathy, adult-onset 10.9
8 autonomic dysfunction 10.5
9 neuropathy 10.4
10 anxiety 10.4
11 olivopontocerebellar atrophy 10.4
12 impotence 10.4
13 peripheral nervous system disease 10.4
14 movement disease 10.3
15 amyotrophic lateral sclerosis 1 10.2
16 strabismus 10.2
17 autism 10.2
18 myeloma, multiple 10.2
19 frontotemporal dementia 10.2
20 neuronal intranuclear inclusion disease 10.2
21 alcohol use disorder 10.2
22 lateral sclerosis 10.2
23 mood disorder 10.2
24 axonal neuropathy 10.2
25 monoclonal gammopathy of uncertain significance 10.2
26 chronic fatigue syndrome 10.2
27 mechanical strabismus 10.2
28 seizure disorder 10.2
29 multiple system atrophy 1 10.2
30 aceruloplasminemia 10.2
31 dementia 10.2
32 myopathy 10.2
33 dysautonomia 10.2
34 head injury 10.2
35 premature ovarian failure 1 10.2
36 essential tremor 10.2
37 parkinson disease, late-onset 10.1
38 spinocerebellar ataxia 10 10.1
39 spinocerebellar ataxia 12 10.1
40 spinocerebellar ataxia 17 10.1
41 major depressive disorder 10.1
42 sleep apnea 10.1
43 autosomal dominant cerebellar ataxia 10.1
44 mental depression 10.1
45 depression 10.1
46 alzheimer disease 10.0
47 erythermalgia, primary 10.0
48 huntington disease 10.0
49 attention deficit-hyperactivity disorder 10.0
50 inclusion body myositis 10.0

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



Diseases related to Fragile X Tremor/ataxia Syndrome
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Symptoms & Phenotypes for Fragile X Tremor/ataxia Syndrome

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Human phenotypes related to Fragile X Tremor/ataxia Syndrome:

58 31 (show all 48)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 depressivity 58 31 Frequent (79-30%) HP:0000716
2 dysarthria 58 31 Very frequent (99-80%) HP:0001260
3 hypothyroidism 58 31 Occasional (29-5%) HP:0000821
4 bowel incontinence 58 31 Occasional (29-5%) HP:0002607
5 memory impairment 58 31 Very frequent (99-80%) HP:0002354
6 myalgia 58 31 Occasional (29-5%) HP:0003326
7 anxiety 58 31 Frequent (79-30%) HP:0000739
8 gait ataxia 58 31 Very frequent (99-80%) HP:0002066
9 dysmetria 58 31 Very frequent (99-80%) HP:0001310
10 intention tremor 58 31 Very frequent (99-80%) HP:0002080
11 dementia 58 31 Very frequent (99-80%) HP:0000726
12 hyporeflexia 58 31 Frequent (79-30%) HP:0001265
13 bradykinesia 58 31 Occasional (29-5%) HP:0002067
14 impotence 58 31 Frequent (79-30%) HP:0000802
15 parkinsonism 58 31 Occasional (29-5%) HP:0001300
16 nystagmus 31 HP:0000639
17 ataxia 58 Very frequent (99-80%)
18 gait disturbance 58 Very frequent (99-80%)
19 dysphagia 58 Occasional (29-5%)
20 hypotension 58 Occasional (29-5%)
21 hypertension 58 Occasional (29-5%)
22 muscle weakness 58 Frequent (79-30%)
23 dysautonomia 58 Frequent (79-30%)
24 hearing impairment 31 HP:0000365
25 cerebral cortical atrophy 58 Very frequent (99-80%)
26 peripheral neuropathy 58 Frequent (79-30%)
27 premature ovarian insufficiency 31 HP:0008209
28 urinary bladder sphincter dysfunction 58 Frequent (79-30%)
29 poor fine motor coordination 31 HP:0007010
30 mask-like facies 31 HP:0000298
31 rigidity 58 Frequent (79-30%)
32 obsessive-compulsive behavior 58 Frequent (79-30%)
33 abnormality of brainstem morphology 58 Occasional (29-5%)
34 dysdiadochokinesis 31 HP:0002075
35 saccadic smooth pursuit 31 HP:0001152
36 postural tremor 31 HP:0002174
37 cerebellar atrophy 31 HP:0001272
38 urinary incontinence 31 HP:0000020
39 pollakisuria 58 Frequent (79-30%)
40 disinhibition 31 HP:0000734
41 diffuse cerebral atrophy 31 HP:0002506
42 obsessive-compulsive trait 31 HP:0008770
43 diffuse cerebellar atrophy 58 Frequent (79-30%)
44 resting tremor 31 HP:0002322
45 dysesthesia 58 Frequent (79-30%)
46 impaired tandem gait 31 HP:0031629
47 inertia 58 Very frequent (99-80%)
48 impaired distal vibration sensation 31 HP:0006886

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Eyes:
nystagmus
saccadic pursuit

Endocrine Features:
hypothyroidism
premature ovarian failure

Neurologic Behavioral Psychiatric Manifestations:
anxiety
disinhibition
depression
executive dysfunction
obsessive-compulsive disorder

Genitourinary External Genitalia Male:
impotence

Head And Neck Ears:
hearing loss

Abdomen Gastrointestinal:
incontinence

Laboratory Abnormalities:
increased intracellular fmrp mrna
decreased intracellular fmr protein

Neurologic Central Nervous System:
dysarthria
dysmetria
intention tremor
dysdiadochokinesis
action tremor
more
Neurologic Peripheral Nervous System:
peripheral neuropathy
hyporeflexia
lower extremity numbness
decreased distal vibratory sensation
lower extremity paresthesias

Genitourinary Bladder:
urinary incontinence

Muscle Soft Tissue:
muscle pain
fibromyalgia

Genitourinary Internal Genitalia Female:
premature ovarian failure

Head And Neck Face:
masked facies

Clinical features from OMIM:

300623

UMLS symptoms related to Fragile X Tremor/ataxia Syndrome:


ataxia, tremor, myalgia, gait ataxia, dysdiadochokinesis, action tremor, bradykinesia, resting tremor, paresthesia lower limb, static tremor, lower extremity numbness
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Drugs & Therapeutics for Fragile X Tremor/ataxia Syndrome

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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 Central Nervous System Depressants Phase 2
3 Anesthetics Phase 2
4 Pharmaceutical Solutions Phase 2
5 Pregnanolone Phase 2 128-20-1
6
Dopamine Approved 51-61-6, 62-31-7 681
7
Memantine Approved, Investigational 19982-08-2 4054
8 Neurotransmitter Agents
9 Dopamine Agents
10 Antiparkinson Agents
11 Excitatory Amino Acids
12 Excitatory Amino Acid Antagonists

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Diaphragmatic Breathing and Heart Rate Variability Training for Improving Hypertension in Fragile X Associated Tremor/Ataxia Completed NCT03816540 Phase 3
2 Treatment of Fragile-X Associated Tremor/Ataxia Syndrome (FXTAS) With Allopregnanolone Completed NCT02603926 Phase 2 Allopregnanolone
3 Phase 2 Study of Citocoline for Treatment in Fragile X-associated Tremor/Ataxia Syndrome Completed NCT02197104 Phase 2 citocoline
4 Characterization and Treatment of CNS Abnormalities in Premutation Carriers: A Double-Blind Placebo-Controlled Trial of Memantine Completed NCT00584948 Memantine;Placebo
5 Mapping Functional Networks of Brain Activity (Brain Network Activation) Based on Analysis of Evoked Response Potential (ERP) Signals and Registration of Posture and Gait-related Data in FMR1 Premutation Carriers and Patients With FXTAS. Recruiting NCT02936531

Search NIH Clinical Center for Fragile X Tremor/ataxia Syndrome

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Genetic Tests for Fragile X Tremor/ataxia Syndrome

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Genetic tests related to Fragile X Tremor/ataxia Syndrome:

# Genetic test Affiliating Genes
1 Fragile X Tremor/ataxia Syndrome 29 FMR1
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Anatomical Context for Fragile X Tremor/ataxia Syndrome

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

40
Brain, Testes, Heart, Cerebellum, Eye, Amygdala, Cortex
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Publications for Fragile X Tremor/ataxia Syndrome

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Articles related to Fragile X Tremor/ataxia Syndrome:

(show top 50) (show all 518)
# Title Authors PMID Year
1
Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X. 56 6
11445641 2001
2
EMQN best practice guidelines for the molecular genetic testing and reporting of fragile X syndrome and other fragile X-associated disorders. 61 6
25227148 2015
3
High apolipoprotein E4 allele frequency in FXTAS patients. 61 56
23492875 2013
4
ACMG Standards and Guidelines for fragile X testing: a revision to the disease-specific supplements to the Standards and Guidelines for Clinical Genetics Laboratories of the American College of Medical Genetics and Genomics. 61 6
23765048 2013
5
Motor and mental dysfunction in mother-daughter transmitted FXTAS. 61 56
20938029 2010
6
Penetrance of marked cognitive impairment in older male carriers of the FMR1 gene premutation. 61 56
19542082 2009
7
Small CGG repeat expansion alleles of FMR1 gene are associated with parkinsonism. 61 56
19796183 2009
8
Ectopic expression of CGG containing mRNA is neurotoxic in mammals. 61 56
19377084 2009
9
Clinical and neuropathologic findings in a woman with the FMR1 premutation and multiple sclerosis. 61 56
18695063 2008
10
Abnormal nerve conduction features in fragile X premutation carriers. 61 56
18413472 2008
11
Expanded clinical phenotype of women with the FMR1 premutation. 61 56
18348275 2008
12
Neuropathy as a presenting feature in fragile X-associated tremor/ataxia syndrome. 61 56
17726686 2007
13
Pur alpha binds to rCGG repeats and modulates repeat-mediated neurodegeneration in a Drosophila model of fragile X tremor/ataxia syndrome. 61 56
17698009 2007
14
RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppress fragile X CGG premutation repeat-induced neurodegeneration in a Drosophila model of FXTAS. 61 56
17698010 2007
15
Volumetric brain changes in females with fragile X-associated tremor/ataxia syndrome (FXTAS). 61 56
17724287 2007
16
Atypical clinical course of FXTAS: rapidly progressive dementia as the major symptom. 61 56
17515552 2007
17
Fragile-X syndrome and fragile X-associated tremor/ataxia syndrome: two faces of FMR1. 61 56
17166801 2007
18
Protein composition of the intranuclear inclusions of FXTAS. 61 56
16246864 2006
19
Neuropathology of fragile X-associated tremor/ataxia syndrome (FXTAS). 61 56
16332642 2006
20
Psychiatric phenotype of the fragile X-associated tremor/ataxia syndrome (FXTAS) in males: newly described fronto-subcortical dementia. 61 56
16426093 2006
21
Induction of inclusion formation and disruption of lamin A/C structure by premutation CGG-repeat RNA in human cultured neural cells. 61 56
16239243 2005
22
Initial diagnoses given to persons with the fragile X associated tremor/ataxia syndrome (FXTAS). 61 56
16043804 2005
23
FMR1 premutations associated with fragile X-associated tremor/ataxia syndrome in multiple system atrophy. 61 56
15956167 2005
24
FMR1 gene premutation is a frequent genetic cause of late-onset sporadic cerebellar ataxia. 61 56
15642922 2005
25
Fragile-X-associated tremor/ataxia syndrome (FXTAS) in females with the FMR1 premutation. 61 56
15065016 2004
26
The fragile-X premutation: a maturing perspective. 61 56
15052536 2004
27
FMR1 Disorders 61 6
20301558 1998
28
EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood. 6
24418350 2014
29
Genetic counseling and testing for FMR1 gene mutations: practice guidelines of the national society of genetic counselors. 6
22797890 2012
30
Clinical utility gene card for: fragile X mental retardation syndrome, fragile X-associated tremor/ataxia syndrome and fragile X-associated primary ovarian insufficiency. 6
21540884 2011
31
Evidence for the toxicity of bidirectional transcripts and mitochondrial dysfunction in blood associated with small CGG expansions in the FMR1 gene in patients with parkinsonism. 56
21270637 2011
32
EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias. 6
20050888 2010
33
No evidence for a difference in neuropsychological profile among carriers and noncarriers of the FMR1 premutation in adults under the age of 50. 56
19026394 2008
34
Fragile X-associated tremor/ataxia syndrome: an aging face of the fragile X gene. 56
18195136 2008
35
Magnetic resonance imaging study in older fragile X premutation male carriers. 56
16049924 2005
36
Long CGG-repeat tracts are toxic to human cells: implications for carriers of Fragile X premutation alleles. 56
15862312 2005
37
RNA-mediated neurodegeneration caused by the fragile X premutation rCGG repeats in Drosophila. 56
12948442 2003
38
Tremor, ataxia and dementia in older men may indicate a carrier of the fragile X syndrome. 56
12791039 2003
39
The FMR1 CGG repeat mouse displays ubiquitin-positive intranuclear neuronal inclusions; implications for the cerebellar tremor/ataxia syndrome. 56
12700164 2003
40
Observation of an excess of fragile-X premutations in a population of males referred with spinocerebellar ataxia. 56
12612802 2003
41
Tremor and ataxia in fragile X premutation carriers: blinded videotape study. 56
12730995 2003
42
Fragile X premutation tremor/ataxia syndrome: molecular, clinical, and neuroimaging correlates. 56
12638084 2003
43
The fragile X premutation presenting as essential tremor. 56
12533098 2003
44
Fragile X premutation is a significant risk factor for premature ovarian failure: the International Collaborative POF in Fragile X study--preliminary data. 6
10208170 1999
45
Studies of FRAXA and FRAXE in women with premature ovarian failure. 6
9719368 1998
46
Analysis of full fragile X mutations in fetal tissues and monozygotic twins indicate that abnormal methylation and somatic heterogeneity are established early in development. 6
1605193 1992
47
Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. 6
1675488 1991
48
The complex phenotype of spinocerebellar ataxia type 48 in eight unrelated Italian families. 61
31571321 2020
49
Developmental aspects of FXAND in a man with the FMR1 premutation. 61
31899609 2020
50
Interaction between ventricular expansion and structural changes in the corpus callosum and putamen in males with FMR1 normal and premutation alleles. 61
31733943 2020
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Variations for Fragile X Tremor/ataxia Syndrome

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

6 ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FMR1 FMR1, (CGG)n REPEAT EXPANSIONNT expansion Pathogenic 9972
2 FMR1 NM_002024.5(FMR1):c.-128_-126GGC(55_200)NT expansion Pathogenic 623467 X:146993570-146993572 X:147912052-147912054
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Expression for Fragile X Tremor/ataxia Syndrome

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

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

36
# 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
RNA transport 36
10.84 RAN FMR1
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GO Terms for Fragile X Tremor/ataxia Syndrome

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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 PURA FMR1

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 PURA FMR1
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Sources for Fragile X Tremor/ataxia Syndrome

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3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
28 GO
29 GTR
30 HMDB
31 HPO
32 ICD10
33 ICD10 via Orphanet
34 ICD9CM
35 IUPHAR
36 KEGG
37 LifeMap
39 LOVD
41 MedGen
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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