FXTAS
MCID: FRG010
MIFTS: 44

Fragile X Tremor/ataxia Syndrome (FXTAS)

Categories: Genetic diseases, Mental 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 57 73 36 29 13 6 39 71
Fxtas 57 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®:

57 (Updated 05-Mar-2021)
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:

Orphanet: 58  
Rare neurological diseases


Summaries for Fragile X Tremor/ataxia Syndrome

OMIM® : 57 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) (Updated 05-Mar-2021)

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 Pregnanolone have been mentioned in the context of this disorder. Affiliated tissues include brain, eye and cerebellum, 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.

Related Diseases for Fragile X Tremor/ataxia Syndrome

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

(show top 50) (show all 85)
# Related Disease Score Top Affiliating Genes
1 fragile x-associated tremor/ataxia syndrome 31.5 PURA FRAXA FMR1-AS1 FMR1
2 tremor 31.2 FRAXA FMR1
3 fmr1 disorders 30.1 FRAXA FMR1
4 learning disability 30.1 PURA FMR1
5 fragile x syndrome 29.6 PURA FRAXA FMR1-AS1 FMR1
6 ataxia and polyneuropathy, adult-onset 10.8
7 neuronal intranuclear inclusion disease 10.5
8 anxiety 10.5
9 olivopontocerebellar atrophy 10.4
10 impotence 10.4
11 autonomic dysfunction 10.3
12 parkinsonism 10.3
13 neuropathy 10.2
14 peripheral nervous system disease 10.2
15 amyotrophic lateral sclerosis 1 10.2
16 strabismus 10.2
17 frontotemporal dementia 10.2
18 mild cognitive impairment 10.2
19 lateral sclerosis 10.2
20 mood disorder 10.2
21 infertility 10.2
22 axonal neuropathy 10.2
23 monoclonal gammopathy of uncertain significance 10.2
24 chronic fatigue syndrome 10.2
25 mechanical strabismus 10.2
26 cerebellar degeneration 10.2
27 seizure disorder 10.2
28 rare movement disorder 10.2
29 multiple system atrophy 1 10.2
30 dementia 10.2
31 myopathy 10.2
32 dysautonomia 10.2
33 head injury 10.2
34 movement disease 10.1
35 premature menopause 10.0
36 essential tremor 10.0
37 parkinson disease, late-onset 9.9
38 major depressive disorder 9.9
39 alacrima, achalasia, and mental retardation syndrome 9.9
40 sleep apnea 9.9
41 autism spectrum disorder 9.9
42 autosomal dominant cerebellar ataxia 9.9
43 mental depression 9.9
44 depression 9.9
45 cerebral atrophy 9.9
46 spinocerebellar ataxia 1 9.9 FRAXA FMR1
47 huntington disease-like 2 9.9 PURA FMR1
48 restless legs syndrome 9.8 FRAXA FMR1
49 dyslexia 9.8 FRAXA FMR1-AS1
50 alzheimer disease 9.8

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:

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 anxiety 58 31 Frequent (79-30%) HP:0000739
6 myalgia 58 31 Occasional (29-5%) HP:0003326
7 dysmetria 58 31 Very frequent (99-80%) HP:0001310
8 hyporeflexia 58 31 Frequent (79-30%) HP:0001265
9 memory impairment 58 31 Very frequent (99-80%) HP:0002354
10 gait ataxia 58 31 Very frequent (99-80%) HP:0002066
11 impotence 58 31 Frequent (79-30%) HP:0000802
12 dementia 58 31 Very frequent (99-80%) HP:0000726
13 intention tremor 58 31 Very frequent (99-80%) HP:0002080
14 parkinsonism 58 31 Occasional (29-5%) HP:0001300
15 bradykinesia 58 31 Occasional (29-5%) HP:0002067
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 premature ovarian insufficiency 31 HP:0008209
26 mask-like facies 31 HP:0000298
27 cerebral cortical atrophy 58 Very frequent (99-80%)
28 obsessive-compulsive behavior 58 Frequent (79-30%)
29 dysdiadochokinesis 31 HP:0002075
30 peripheral neuropathy 58 Frequent (79-30%)
31 cerebellar atrophy 31 HP:0001272
32 rigidity 58 Frequent (79-30%)
33 disinhibition 31 HP:0000734
34 poor fine motor coordination 31 HP:0007010
35 urinary incontinence 31 HP:0000020
36 abnormality of brainstem morphology 58 Occasional (29-5%)
37 saccadic smooth pursuit 31 HP:0001152
38 pollakisuria 58 Frequent (79-30%)
39 impaired tandem gait 31 HP:0031629
40 dysesthesia 58 Frequent (79-30%)
41 urinary bladder sphincter dysfunction 58 Frequent (79-30%)
42 inertia 58 Very frequent (99-80%)
43 diffuse cerebellar atrophy 58 Frequent (79-30%)
44 diffuse cerebral atrophy 31 HP:0002506
45 postural tremor 31 HP:0002174
46 resting tremor 31 HP:0002322
47 impaired distal vibration sensation 31 HP:0006886
48 obsessive-compulsive trait 31 HP:0008770

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Mar-2021)
Head And Neck Eyes:
nystagmus
saccadic pursuit

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

Laboratory Abnormalities:
increased intracellular fmrp mrna
decreased intracellular fmr protein

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

Genitourinary External Genitalia Male:
impotence

Muscle Soft Tissue:
muscle pain
fibromyalgia

Genitourinary Internal Genitalia Female:
premature ovarian failure

Head And Neck Face:
masked facies

Clinical features from OMIM®:

300623 (Updated 05-Mar-2021)

UMLS symptoms related to Fragile X Tremor/ataxia Syndrome:


ataxia, tremor, myalgia, dysdiadochokinesis, gait ataxia, bradykinesia, resting tremor, action 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 10)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Progesterone Approved, Vet_approved Phase 2 57-83-0 5994
2
Pregnanolone Investigational Phase 2 128-20-1 31402
3 Anesthetics Phase 2
4 Pharmaceutical Solutions Phase 2
5
Memantine Approved, Investigational 19982-08-2 4054
6
Dopamine Approved 51-61-6, 62-31-7 681
7 Neurotransmitter Agents
8 Dopamine Agents
9 Antiparkinson Agents
10 Excitatory Amino Acid Antagonists

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 Phase 2 Study of Citocoline for Treatment in Fragile X-associated Tremor/Ataxia Syndrome Completed NCT02197104 Phase 2 citocoline
3 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. Unknown status NCT02936531
4 Characterization and Treatment of CNS Abnormalities in Premutation Carriers: A Double-Blind Placebo-Controlled Trial of Memantine Completed NCT00584948 Memantine;Placebo
5 A Pilot Dual-Task Treadmill Training to Improve Gait and Balance in Fragile X-Associated Tremor/Ataxia Syndrome Recruiting NCT04428567

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 29 FMR1

Anatomical Context for Fragile X Tremor/ataxia Syndrome

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

40
Brain, Eye, Cerebellum, Cortex, Amygdala, Adrenal Gland, Hypothalamus

Publications for Fragile X Tremor/ataxia Syndrome

Articles related to Fragile X Tremor/ataxia Syndrome:

(show top 50) (show all 570)
# Title Authors PMID Year
1
Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X. 57 6
11445641 2001
2
High apolipoprotein E4 allele frequency in FXTAS patients. 61 57
23492875 2013
3
Motor and mental dysfunction in mother-daughter transmitted FXTAS. 61 57
20938029 2010
4
Penetrance of marked cognitive impairment in older male carriers of the FMR1 gene premutation. 57 61
19542082 2009
5
Small CGG repeat expansion alleles of FMR1 gene are associated with parkinsonism. 57 61
19796183 2009
6
Ectopic expression of CGG containing mRNA is neurotoxic in mammals. 57 61
19377084 2009
7
Clinical and neuropathologic findings in a woman with the FMR1 premutation and multiple sclerosis. 57 61
18695063 2008
8
Expanded clinical phenotype of women with the FMR1 premutation. 61 57
18348275 2008
9
Abnormal nerve conduction features in fragile X premutation carriers. 57 61
18413472 2008
10
Neuropathy as a presenting feature in fragile X-associated tremor/ataxia syndrome. 57 61
17726686 2007
11
Volumetric brain changes in females with fragile X-associated tremor/ataxia syndrome (FXTAS). 57 61
17724287 2007
12
Pur alpha binds to rCGG repeats and modulates repeat-mediated neurodegeneration in a Drosophila model of fragile X tremor/ataxia syndrome. 61 57
17698009 2007
13
RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppress fragile X CGG premutation repeat-induced neurodegeneration in a Drosophila model of FXTAS. 61 57
17698010 2007
14
Atypical clinical course of FXTAS: rapidly progressive dementia as the major symptom. 61 57
17515552 2007
15
Psychiatric phenotype of the fragile X-associated tremor/ataxia syndrome (FXTAS) in males: newly described fronto-subcortical dementia. 57 61
16426093 2006
16
Protein composition of the intranuclear inclusions of FXTAS. 57 61
16246864 2006
17
Neuropathology of fragile X-associated tremor/ataxia syndrome (FXTAS). 61 57
16332642 2006
18
Induction of inclusion formation and disruption of lamin A/C structure by premutation CGG-repeat RNA in human cultured neural cells. 61 57
16239243 2005
19
Initial diagnoses given to persons with the fragile X associated tremor/ataxia syndrome (FXTAS). 57 61
16043804 2005
20
FMR1 premutations associated with fragile X-associated tremor/ataxia syndrome in multiple system atrophy. 61 57
15956167 2005
21
FMR1 gene premutation is a frequent genetic cause of late-onset sporadic cerebellar ataxia. 57 61
15642922 2005
22
Fragile-X-associated tremor/ataxia syndrome (FXTAS) in females with the FMR1 premutation. 61 57
15065016 2004
23
The fragile-X premutation: a maturing perspective. 61 57
15052536 2004
24
NOTCH2NLC-linked neuronal intranuclear inclusion body disease and fragile X-associated tremor/ataxia syndrome. 57
32789443 2020
25
Clinicopathological features of adult-onset neuronal intranuclear inclusion disease. 57
27797808 2016
26
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. 57
21270637 2011
27
No evidence for a difference in neuropsychological profile among carriers and noncarriers of the FMR1 premutation in adults under the age of 50. 57
19026394 2008
28
Fragile X-associated tremor/ataxia syndrome: an aging face of the fragile X gene. 57
18195136 2008
29
Magnetic resonance imaging study in older fragile X premutation male carriers. 57
16049924 2005
30
Long CGG-repeat tracts are toxic to human cells: implications for carriers of Fragile X premutation alleles. 57
15862312 2005
31
RNA-mediated neurodegeneration caused by the fragile X premutation rCGG repeats in Drosophila. 57
12948442 2003
32
Tremor, ataxia and dementia in older men may indicate a carrier of the fragile X syndrome. 57
12791039 2003
33
Observation of an excess of fragile-X premutations in a population of males referred with spinocerebellar ataxia. 57
12612802 2003
34
Tremor and ataxia in fragile X premutation carriers: blinded videotape study. 57
12730995 2003
35
The FMR1 CGG repeat mouse displays ubiquitin-positive intranuclear neuronal inclusions; implications for the cerebellar tremor/ataxia syndrome. 57
12700164 2003
36
Fragile X premutation tremor/ataxia syndrome: molecular, clinical, and neuroimaging correlates. 57
12638084 2003
37
The fragile X premutation presenting as essential tremor. 57
12533098 2003
38
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
39
Studies of FRAXA and FRAXE in women with premature ovarian failure. 6
9719368 1998
40
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
41
Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. 6
1675488 1991
42
Heterogeneous Nuclear Ribonucleoproteins: Implications in Neurological Diseases. 61
33000450 2021
43
Repeat RNA expansion disorders of the nervous system: post-transcriptional mechanisms and therapeutic strategies. 61
33172304 2021
44
Attitudes toward population screening among people living with fragile X syndrome in the UK: 'I wouldn't wish him away, I'd just wish his fragile X syndrome away'. 61
33184995 2021
45
Fragile X syndrome full mutation in cognitively normal male identified as part of an Australian reproductive carrier screening program. 61
33544979 2021
46
Abundancy of polymorphic CGG repeats in the human genome suggest a broad involvement in neurological disease. 61
33510257 2021
47
Premutations in the FMR1 gene in Serbian patients with undetermined tremor, ataxia and parkinsonism. 61
33403926 2021
48
CGG repeat RNA G-quadruplexes interact with FMRpolyG to cause neuronal dysfunction in fragile X-related tremor/ataxia syndrome. 61
33523882 2021
49
Brain 18F-FDG and 18F-Flumetamol PET Imaging of Fragile X-Associated Tremor Ataxia Syndrome. 61
33443951 2021
50
Expression of expanded FMR1-CGG repeats alters mitochondrial miRNAs and modulates mitochondrial functions and cell death in cellular model of FXTAS. 61
33497798 2021

Variations for Fragile X Tremor/ataxia Syndrome

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 EXPANSION Microsatellite Pathogenic 9972
2 FMR1 NM_002024.5(FMR1):c.-128_-126GGC(55_200) Microsatellite Pathogenic 623467 X:146993570-146993572 X:147912052-147912054

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:

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 10.89 RAN FMR1

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 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

Sources for Fragile X Tremor/ataxia Syndrome

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
20 GARD
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
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
53 NINDS
54 Novoseek
56 OMIM via Orphanet
57 OMIM® (Updated 05-Mar-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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