FXTAS
MCID: FRG010
MIFTS: 43

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 74 37 29 13 6 40 72
Fxtas 57 74
Fragile X-Associated Tremor/ataxia Syndrome 59
Fxtas Syndrome 59

Characteristics:

Orphanet epidemiological data:

59
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
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:

32
fragile x tremor/ataxia syndrome:
Onset and clinical course adult onset
Inheritance x-linked dominant inheritance


Classifications:

Orphanet: 59  
Rare neurological diseases


External Ids:

OMIM 57 300623
KEGG 37 H01731
ICD10 via Orphanet 34 G11.2
UMLS via Orphanet 73 C1839780 C3164069
Orphanet 59 ORPHA93256
MedGen 42 C1839780
UMLS 72 C1839780

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)

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 Pharmaceutical Solutions have been mentioned in the context of this disorder. Affiliated tissues include brain, testes and heart, and related phenotypes are depressivity and hypothyroidism

KEGG : 37
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 : 74 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 76)
# Related Disease Score Top Affiliating Genes
1 fragile x-associated tremor/ataxia syndrome 32.9 LOC108684022 FMR1
2 tremor 31.2 LOC108684022 FMR1
3 learning disability 29.8 PURA FMR1
4 fragile x syndrome 29.7 LOC108684022 FMR1-AS1 FMR1
5 alacrima, achalasia, and mental retardation syndrome 29.1 PURA FMR1
6 ataxia and polyneuropathy, adult-onset 10.9
7 autonomic dysfunction 10.5
8 autism spectrum disorder 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 fmr1-related disorders 10.3
15 movement disease 10.3
16 amyotrophic lateral sclerosis 1 10.2
17 attention deficit-hyperactivity disorder 10.2
18 strabismus 10.2
19 autism 10.2
20 myeloma, multiple 10.2
21 aging 10.2
22 frontotemporal dementia 10.2
23 neuronal intranuclear inclusion disease 10.2
24 alcohol use disorder 10.2
25 lateral sclerosis 10.2
26 mood disorder 10.2
27 axonal neuropathy 10.2
28 monoclonal gammopathy of uncertain significance 10.2
29 chronic fatigue syndrome 10.2
30 mechanical strabismus 10.2
31 seizure disorder 10.2
32 multiple system atrophy 1 10.2
33 aceruloplasminemia 10.2
34 dementia 10.2
35 myopathy 10.2
36 dysautonomia 10.2
37 head injury 10.2
38 premature ovarian failure 1 10.2
39 essential tremor 10.2
40 alzheimer disease 10.1
41 parkinson disease, late-onset 10.1
42 spinocerebellar ataxia 10 10.1
43 spinocerebellar ataxia 12 10.1
44 spinocerebellar ataxia 17 10.1
45 major depressive disorder 10.1
46 sleep apnea 10.1
47 autosomal dominant cerebellar ataxia 10.1
48 mental depression 10.1
49 depression 10.1
50 erythermalgia, primary 10.0

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:

59 32 (show all 48)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 depressivity 59 32 Frequent (79-30%) HP:0000716
2 hypothyroidism 59 32 Occasional (29-5%) HP:0000821
3 dysarthria 59 32 Very frequent (99-80%) HP:0001260
4 bowel incontinence 59 32 Occasional (29-5%) HP:0002607
5 memory impairment 59 32 Very frequent (99-80%) HP:0002354
6 myalgia 59 32 Occasional (29-5%) HP:0003326
7 anxiety 59 32 Frequent (79-30%) HP:0000739
8 gait ataxia 59 32 Very frequent (99-80%) HP:0002066
9 dysmetria 59 32 Very frequent (99-80%) HP:0001310
10 intention tremor 59 32 Very frequent (99-80%) HP:0002080
11 dementia 59 32 Very frequent (99-80%) HP:0000726
12 hyporeflexia 59 32 Frequent (79-30%) HP:0001265
13 bradykinesia 59 32 Occasional (29-5%) HP:0002067
14 impotence 59 32 Frequent (79-30%) HP:0000802
15 parkinsonism 59 32 Occasional (29-5%) HP:0001300
16 nystagmus 32 HP:0000639
17 hypertension 59 Occasional (29-5%)
18 ataxia 59 Very frequent (99-80%)
19 gait disturbance 59 Very frequent (99-80%)
20 muscle weakness 59 Frequent (79-30%)
21 dysphagia 59 Occasional (29-5%)
22 dysautonomia 59 Frequent (79-30%)
23 hypotension 59 Occasional (29-5%)
24 hearing impairment 32 HP:0000365
25 peripheral neuropathy 59 Frequent (79-30%)
26 premature ovarian insufficiency 32 HP:0008209
27 urinary bladder sphincter dysfunction 59 Frequent (79-30%)
28 poor fine motor coordination 32 HP:0007010
29 mask-like facies 32 HP:0000298
30 cerebral cortical atrophy 59 Very frequent (99-80%)
31 rigidity 59 Frequent (79-30%)
32 obsessive-compulsive behavior 59 Frequent (79-30%)
33 dysdiadochokinesis 32 HP:0002075
34 saccadic smooth pursuit 32 HP:0001152
35 postural tremor 32 HP:0002174
36 cerebellar atrophy 32 HP:0001272
37 urinary incontinence 32 HP:0000020
38 pollakisuria 59 Frequent (79-30%)
39 abnormality of brainstem morphology 59 Occasional (29-5%)
40 disinhibition 32 HP:0000734
41 diffuse cerebral atrophy 32 HP:0002506
42 obsessive-compulsive trait 32 HP:0008770
43 diffuse cerebellar atrophy 59 Frequent (79-30%)
44 resting tremor 32 HP:0002322
45 dysesthesia 59 Frequent (79-30%)
46 inertia 59 Very frequent (99-80%)
47 impaired distal vibration sensation 32 HP:0006886
48 impaired tandem gait 32 HP:0031629

Symptoms via clinical synopsis from OMIM:

57
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

Head And Neck Ears:
hearing loss

Abdomen Gastrointestinal:
incontinence

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

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

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 Pharmaceutical Solutions Phase 2
3 Central Nervous System Depressants Phase 2
4 Anesthetics 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 Acid Antagonists
12 Excitatory Amino Acids

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 Recruiting 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

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:

41
Brain, Testes, Heart, Cerebellum, Eye, Amygdala, Cortex

Publications for Fragile X Tremor/ataxia Syndrome

Articles related to Fragile X Tremor/ataxia Syndrome:

(show top 50) (show all 498)
# Title Authors PMID Year
1
Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X. 8 71
11445641 2001
2
EMQN best practice guidelines for the molecular genetic testing and reporting of fragile X syndrome and other fragile X-associated disorders. 38 71
25227148 2015
3
High apolipoprotein E4 allele frequency in FXTAS patients. 38 8
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. 38 71
23765048 2013
5
Motor and mental dysfunction in mother-daughter transmitted FXTAS. 38 8
20938029 2010
6
Penetrance of marked cognitive impairment in older male carriers of the FMR1 gene premutation. 38 8
19542082 2009
7
Small CGG repeat expansion alleles of FMR1 gene are associated with parkinsonism. 38 8
19796183 2009
8
Ectopic expression of CGG containing mRNA is neurotoxic in mammals. 38 8
19377084 2009
9
Clinical and neuropathologic findings in a woman with the FMR1 premutation and multiple sclerosis. 38 8
18695063 2008
10
Abnormal nerve conduction features in fragile X premutation carriers. 38 8
18413472 2008
11
Expanded clinical phenotype of women with the FMR1 premutation. 38 8
18348275 2008
12
Neuropathy as a presenting feature in fragile X-associated tremor/ataxia syndrome. 38 8
17726686 2007
13
RNA-binding proteins hnRNP A2/B1 and CUGBP1 suppress fragile X CGG premutation repeat-induced neurodegeneration in a Drosophila model of FXTAS. 38 8
17698010 2007
14
Pur alpha binds to rCGG repeats and modulates repeat-mediated neurodegeneration in a Drosophila model of fragile X tremor/ataxia syndrome. 38 8
17698009 2007
15
Volumetric brain changes in females with fragile X-associated tremor/ataxia syndrome (FXTAS). 38 8
17724287 2007
16
Atypical clinical course of FXTAS: rapidly progressive dementia as the major symptom. 38 8
17515552 2007
17
Fragile-X syndrome and fragile X-associated tremor/ataxia syndrome: two faces of FMR1. 38 8
17166801 2007
18
Psychiatric phenotype of the fragile X-associated tremor/ataxia syndrome (FXTAS) in males: newly described fronto-subcortical dementia. 38 8
16426093 2006
19
Neuropathology of fragile X-associated tremor/ataxia syndrome (FXTAS). 38 8
16332642 2006
20
Protein composition of the intranuclear inclusions of FXTAS. 38 8
16246864 2006
21
Induction of inclusion formation and disruption of lamin A/C structure by premutation CGG-repeat RNA in human cultured neural cells. 38 8
16239243 2005
22
Initial diagnoses given to persons with the fragile X associated tremor/ataxia syndrome (FXTAS). 38 8
16043804 2005
23
FMR1 premutations associated with fragile X-associated tremor/ataxia syndrome in multiple system atrophy. 38 8
15956167 2005
24
FMR1 gene premutation is a frequent genetic cause of late-onset sporadic cerebellar ataxia. 38 8
15642922 2005
25
The fragile-X premutation: a maturing perspective. 38 8
15052536 2004
26
Fragile-X-associated tremor/ataxia syndrome (FXTAS) in females with the FMR1 premutation. 38 8
15065016 2004
27
FMR1-Related Disorders 38 71
20301558 1998
28
EFNS/ENS Consensus on the diagnosis and management of chronic ataxias in adulthood. 71
24418350 2014
29
Genetic counseling and testing for FMR1 gene mutations: practice guidelines of the national society of genetic counselors. 71
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. 71
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. 8
21270637 2011
32
EFNS guidelines on the molecular diagnosis of ataxias and spastic paraplegias. 71
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. 8
19026394 2008
34
Fragile X-associated tremor/ataxia syndrome: an aging face of the fragile X gene. 8
18195136 2008
35
Magnetic resonance imaging study in older fragile X premutation male carriers. 8
16049924 2005
36
Long CGG-repeat tracts are toxic to human cells: implications for carriers of Fragile X premutation alleles. 8
15862312 2005
37
RNA-mediated neurodegeneration caused by the fragile X premutation rCGG repeats in Drosophila. 8
12948442 2003
38
Tremor, ataxia and dementia in older men may indicate a carrier of the fragile X syndrome. 8
12791039 2003
39
The FMR1 CGG repeat mouse displays ubiquitin-positive intranuclear neuronal inclusions; implications for the cerebellar tremor/ataxia syndrome. 8
12700164 2003
40
Tremor and ataxia in fragile X premutation carriers: blinded videotape study. 8
12730995 2003
41
Observation of an excess of fragile-X premutations in a population of males referred with spinocerebellar ataxia. 8
12612802 2003
42
Fragile X premutation tremor/ataxia syndrome: molecular, clinical, and neuroimaging correlates. 8
12638084 2003
43
The fragile X premutation presenting as essential tremor. 8
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. 71
10208170 1999
45
Studies of FRAXA and FRAXE in women with premature ovarian failure. 71
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. 71
1605193 1992
47
Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. 71
1675488 1991
48
New pathologic mechanisms in nucleotide repeat expansion disorders. 38
31229686 2019
49
Functional motor control deficits in older FMR1 premutation carriers. 38
31161414 2019
50
Reduced caudate volume and cognitive slowing in men at risk of fragile X-associated tremor ataxia syndrome. 38
30046972 2019

Variations for Fragile X Tremor/ataxia Syndrome

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

6
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 FMR1 FMR1, (CGG)n EXPANSION NT expansion Pathogenic
2 FMR1 NM_002024.5(FMR1): c.-128_-126GGC(55_200) NT expansion Pathogenic 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:

37
# 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 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
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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