FXTAS
MCID: FRG008
MIFTS: 44

Fragile X-Associated Tremor/ataxia Syndrome (FXTAS)

Categories: Genetic diseases, Mental diseases, Neuronal diseases

Aliases & Classifications for Fragile X-Associated Tremor/ataxia Syndrome

MalaCards integrated aliases for Fragile X-Associated Tremor/ataxia Syndrome:

Name: Fragile X-Associated Tremor/ataxia Syndrome 12 43 6 15
Fragile X Tremor/ataxia Syndrome 43 70
Fxtas Syndrome 12
Fxtas 43

Classifications:



Summaries for Fragile X-Associated Tremor/ataxia Syndrome

MedlinePlus Genetics : 43 Fragile X-associated tremor/ataxia syndrome (FXTAS) is characterized by problems with movement and thinking ability (cognition). FXTAS is a late-onset disorder, usually occurring after age 50, and its signs and symptoms worsen with age. This condition affects males more frequently and severely than females. Affected individuals have areas of damage in the part of the brain that controls movement (the cerebellum) and in a type of brain tissue known as white matter, which can be seen with magnetic resonance imaging (MRI). This damage leads to the movement problems and other impairments associated with FXTAS.The characteristic features of FXTAS are intention tremor, which is trembling or shaking of a limb when trying to perform a voluntary movement such as reaching for an object, and problems with coordination and balance (ataxia). Typically, intention tremors will develop first, followed a few years later by ataxia, although not everyone with FXTAS has both features. Many affected individuals develop other movement problems, such as a pattern of movement abnormalities known as parkinsonism, which includes tremors when not moving (resting tremor), rigidity, and unusually slow movement (bradykinesia). In addition, affected individuals may have reduced sensation, numbness or tingling, pain, or muscle weakness in the lower limbs (peripheral neuropathy). Some people with FXTAS experience problems with the autonomic nervous system, which controls involuntary body functions, leading to the inability to control the bladder or bowel.People with FXTAS commonly have cognitive disabilities. They may develop short-term memory loss and loss of executive function, which is the ability to plan and implement actions and develop problem-solving strategies. Loss of this function impairs skills such as impulse control, self-monitoring, focusing attention appropriately, and cognitive flexibility. Many people with FXTAS experience anxiety, depression, moodiness, or irritability.Some women develop immune system disorders, such as hypothyroidism or fibromyalgia, before the signs and symptoms of FXTAS appear.

MalaCards based summary : Fragile X-Associated Tremor/ataxia Syndrome, also known as fragile x tremor/ataxia syndrome, is related to fragile x tremor/ataxia syndrome and fmr1 disorders, and has symptoms including ataxia, tremor and myalgia. An important gene associated with Fragile X-Associated Tremor/ataxia Syndrome is FRAXA (Fragile Site, Folic Acid Type, Rare, Fra(X)(Q27.3) A (Macroorchidism, Mental Retardation)), and among its related pathways/superpathways is Translational Control. The drugs Progesterone and Pregnanolone have been mentioned in the context of this disorder. Affiliated tissues include brain, cerebellum and eye, and related phenotypes are dysarthria and cerebral cortical atrophy

Disease Ontology : 12 A X-linked hereditary ataxia that is characterized by adult-onset progressive intention tremor and gait ataxia, has material basis in expanded trinucleotide repeat of the FMR1 gene that results in a toxic gain of function of FMR1 RNA.

Related Diseases for Fragile X-Associated Tremor/ataxia Syndrome

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

(show top 50) (show all 105)
# Related Disease Score Top Affiliating Genes
1 fragile x tremor/ataxia syndrome 33.0 PURA LOC107032825 FRAXA FMR1-AS1 FMR1
2 fmr1 disorders 31.7 FRAXA FMR1
3 fragile x syndrome 30.7 PURA MBNL1 LOC107032825 KHDRBS1 HNRNPA2B1 GRM5
4 spinocerebellar ataxia 36 30.1 NOP56 C9orf72 ATXN10
5 neuromuscular disease 29.8 MBNL1 FXN DMPK CELF1 C9orf72
6 autosomal dominant cerebellar ataxia 29.8 NOP56 MBNL1 FXN FMR1 DMPK CELF1
7 ataxia and polyneuropathy, adult-onset 11.4
8 tremor 11.4
9 parkinsonism 11.0
10 neuropathy 10.8
11 peripheral nervous system disease 10.8
12 autonomic dysfunction 10.8
13 movement disease 10.7
14 essential tremor 10.6
15 supranuclear palsy, progressive, 1 10.5
16 premature menopause 10.5
17 dysautonomia 10.5
18 alzheimer disease 10.4
19 neuronal intranuclear inclusion disease 10.4
20 anxiety 10.4
21 alacrima, achalasia, and mental retardation syndrome 10.4
22 autism spectrum disorder 10.4
23 hypothyroidism 10.4
24 cerebral atrophy 10.4
25 multiple system atrophy 1 10.4
26 parkinson disease, late-onset 10.4
27 dementia 10.4
28 olivopontocerebellar atrophy 10.4
29 alcohol use disorder 10.4
30 impotence 10.4
31 pathologic nystagmus 10.4
32 dementia - subcortical 10.4
33 myotonic dystrophy 10.3 MBNL1 DMPK CELF1
34 spinocerebellar ataxia 1 10.3 FXN FRAXA FMR1 ATXN10
35 premature ovarian failure 1 10.3 LOC107032825 KHDRBS1 FRAXA FMR1
36 spinocerebellar ataxia 37 10.3 NOP56 ATXN10
37 spinocerebellar ataxia 31 10.3 NOP56 C9orf72 ATXN10
38 specific developmental disorder 10.3 GRM5 FMR1 C9orf72
39 mental retardation, x-linked, with cerebellar hypoplasia and distinctive facial appearance 10.3 FXN FMR1
40 hereditary ataxia 10.3 SLC1A3 NOP56 FXN ATXN10
41 spinocerebellar ataxia 30 10.3 NOP56 ATXN10
42 echolalia 10.2 FMR1 C9orf72
43 lens disease 10.2 MBNL1 DMPK CELF1
44 amyotrophic lateral sclerosis 1 10.2
45 erythermalgia, primary 10.2
46 huntington disease 10.2
47 attention deficit-hyperactivity disorder 10.2
48 strabismus 10.2
49 torticollis 10.2
50 frontotemporal dementia 10.2

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



Diseases related to Fragile X-Associated Tremor/ataxia Syndrome

Symptoms & Phenotypes for Fragile X-Associated Tremor/ataxia Syndrome

Human phenotypes related to Fragile X-Associated Tremor/ataxia Syndrome:

31 (show all 29)
# Description HPO Frequency HPO Source Accession
1 dysarthria 31 hallmark (90%) HP:0001260
2 cerebral cortical atrophy 31 hallmark (90%) HP:0002120
3 dysmetria 31 hallmark (90%) HP:0001310
4 memory impairment 31 hallmark (90%) HP:0002354
5 gait ataxia 31 hallmark (90%) HP:0002066
6 dementia 31 hallmark (90%) HP:0000726
7 intention tremor 31 hallmark (90%) HP:0002080
8 inertia 31 hallmark (90%) HP:0030216
9 depressivity 31 frequent (33%) HP:0000716
10 muscle weakness 31 frequent (33%) HP:0001324
11 anxiety 31 frequent (33%) HP:0000739
12 obsessive-compulsive behavior 31 frequent (33%) HP:0000722
13 hyporeflexia 31 frequent (33%) HP:0001265
14 rigidity 31 frequent (33%) HP:0002063
15 impotence 31 frequent (33%) HP:0000802
16 pollakisuria 31 frequent (33%) HP:0100515
17 dysesthesia 31 frequent (33%) HP:0012534
18 urinary bladder sphincter dysfunction 31 frequent (33%) HP:0002839
19 diffuse cerebellar atrophy 31 frequent (33%) HP:0100275
20 abnormal autonomic nervous system physiology 31 frequent (33%) HP:0012332
21 dysphagia 31 occasional (7.5%) HP:0002015
22 hypotension 31 occasional (7.5%) HP:0002615
23 hypothyroidism 31 occasional (7.5%) HP:0000821
24 hypertension 31 occasional (7.5%) HP:0000822
25 bowel incontinence 31 occasional (7.5%) HP:0002607
26 myalgia 31 occasional (7.5%) HP:0003326
27 abnormality of brainstem morphology 31 occasional (7.5%) HP:0002363
28 parkinsonism 31 occasional (7.5%) HP:0001300
29 bradykinesia 31 occasional (7.5%) HP:0002067

UMLS symptoms related to Fragile X-Associated 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-Associated Tremor/ataxia Syndrome

Drugs for Fragile X-Associated 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
Dopamine Approved 62-31-7, 51-61-6 681
6
Memantine Approved, Investigational 19982-08-2 4054
7 Neurotransmitter Agents
8 Dopamine Agents
9 Excitatory Amino Acid Antagonists
10 Antiparkinson Agents

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 Characterization and Treatment of CNS Abnormalities in Premutation Carriers: A Double-Blind Placebo-Controlled Trial of Memantine Completed NCT00584948 Memantine;Placebo
4 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
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-Associated Tremor/ataxia Syndrome

Genetic Tests for Fragile X-Associated Tremor/ataxia Syndrome

Anatomical Context for Fragile X-Associated Tremor/ataxia Syndrome

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

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

Publications for Fragile X-Associated Tremor/ataxia Syndrome

Articles related to Fragile X-Associated Tremor/ataxia Syndrome:

(show top 50) (show all 615)
# Title Authors PMID Year
1
Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X. 6
11445641 2001
2
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
3
Studies of FRAXA and FRAXE in women with premature ovarian failure. 6
9719368 1998
4
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
5
Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. 6
1675488 1991
6
The Effects of Dual Task Cognitive Interference and Fast-Paced Walking on Gait, Turns, and Falls in Men and Women with FXTAS. 61
33118140 2021
7
Laboratory testing for fragile X, 2021 revision: a technical standard of the American College of Medical Genetics and Genomics (ACMG). 61
33795824 2021
8
Premutations in the FMR1 gene in Serbian patients with undetermined tremor, ataxia and parkinsonism. 61
33403926 2021
9
Fragile X Premutation rCGG Repeats Impair Synaptic Growth and Synaptic Transmission at Drosophila larval Neuromuscular Junction. 61
33772546 2021
10
Cerebral Microbleeds in Fragile X-Associated Tremor/Ataxia Syndrome. 61
33760253 2021
11
'Essential Tremor' Phenotype in FMR1 Premutation/Gray Zone Sibling Series: Exploring Possible Genetic Modifiers. 61
33757613 2021
12
Expression of expanded FMR1-CGG repeats alters mitochondrial miRNAs and modulates mitochondrial functions and cell death in cellular model of FXTAS. 61
33497798 2021
13
Repeat RNA expansion disorders of the nervous system: post-transcriptional mechanisms and therapeutic strategies. 61
33172304 2021
14
Heterogeneous Nuclear Ribonucleoproteins: Implications in Neurological Diseases. 61
33000450 2021
15
Assessment of Ataxia Rating Scales and Cerebellar Functional Tests: Critique and Recommendations. 61
33022077 2021
16
Short antisense oligonucleotides alleviate the pleiotropic toxicity of RNA harboring expanded CGG repeats. 61
33627639 2021
17
Abundancy of polymorphic CGG repeats in the human genome suggest a broad involvement in neurological disease. 61
33510257 2021
18
Fragile X premutation and associated health conditions: A review. 61
33443313 2021
19
The Molecular Function of PURA and Its Implications in Neurological Diseases. 61
33777106 2021
20
Brain 18F-FDG and 18F-Flumetamol PET Imaging of Fragile X-Associated Tremor Ataxia Syndrome. 61
33443951 2021
21
Neuropathology of FMR1-premutation carriers presenting with dementia and neuropsychiatric symptoms. 61
33709078 2021
22
The Role of Glutamate in Language and Language Disorders - Evidence from ERP and Pharmacologic Studies. 61
33039453 2020
23
Advances in repeat expansion diseases and a new concept of repeat motif-phenotype correlation. 61
32777681 2020
24
Upper and Lower Limb Movement Kinematics in Aging FMR1 Gene Premutation Carriers. 61
33374331 2020
25
Metabolic profiling reveals dysregulated lipid metabolism and potential biomarkers associated with the development and progression of Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS). 61
33131090 2020
26
The emerging molecular mechanisms for mitochondrial dysfunctions in FXTAS. 61
32800941 2020
27
Health knowledge of women with a fragile X premutation: Improving understanding with targeted educational material. 61
31999047 2020
28
Genetic and Pathological Characteristic Patterns of a Family With Neuronal Intranuclear Inclusion Disease. 61
33271601 2020
29
Neuropathology of a case of fragile X-associated tremor ataxia syndrome without tremor. 61
32830366 2020
30
Study of telomere length in men who carry a fragile X premutation or full mutation allele. 61
32533363 2020
31
Label-free Electrochemical Detection of CGG Repeats on Inkjet Printable 2D Layers of MoS2. 61
33151065 2020
32
Women with Fragile X-associated Tremor/Ataxia Syndrome. 61
33163562 2020
33
Prodromal Markers of Upper Limb Deficits in FMR1 Premutation Carriers and Quantitative Outcome Measures for Future Clinical Trials in Fragile X-associated Tremor/Ataxia Syndrome. 61
33043077 2020
34
Eye Movements in Fragile X-Associated Tremor/Ataxia Syndrome. 61
33110011 2020
35
The molecular mechanisms that underlie fragile X-associated premature ovarian insufficiency: is it RNA or protein based? 61
32777047 2020
36
Fragile-X-Associated Tremor/Ataxia Syndrome or Alcohol-Induced Cerebellar Degeneration? A Case Report. 61
33442376 2020
37
Neddylation activity modulates the neurodegeneration associated with fragile X associated tremor/ataxia syndrome (FXTAS) through regulating Sima. 61
32653676 2020
38
NOTCH2NLC-linked neuronal intranuclear inclusion body disease and fragile X-associated tremor/ataxia syndrome. 61
32789443 2020
39
Fragile X Gray Zone Alleles Are Associated With Signs of Parkinsonism and Earlier Death. 61
32463542 2020
40
Quantification of Neural Activity in FMR1 Premutation Carriers during a Dynamic Sway Task using Source Localization. 61
33018615 2020
41
FMR1 locus isoforms: potential biomarker candidates in fragile X-associated tremor/ataxia syndrome (FXTAS). 61
32632326 2020
42
Decreased Theta Power Reflects Disruption in Postural Control Networks of Fragile X Premutation Carriers. 61
33018599 2020
43
Autofluorescence-based analyses of intranuclear inclusions of Fragile X-associated tremor/ataxia syndrome. 61
32486839 2020
44
Elevated FMR1-mRNA and lowered FMRP - A double-hit mechanism for psychiatric features in men with FMR1 premutations. 61
32576818 2020
45
An explanation of the mechanisms underlying fragile X-associated premature ovarian insufficiency. 61
32377997 2020
46
Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS): Pathophysiology and Clinical Implications. 61
32575683 2020
47
Mothball ingestion as a manifestation of pica, leading to paradichlorobenzene CNS toxicity. 61
33163061 2020
48
Role of mitochondrial DNA variants in the development of fragile X-associated tremor/ataxia syndrome. 61
32173566 2020
49
Ataxia as the Major Manifestation of Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS): Case Series. 61
32466255 2020
50
Fragile X associated neuropsychiatric disorders in a male without FXTAS. 61
32494560 2020

Variations for Fragile X-Associated Tremor/ataxia Syndrome

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

6
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 FMR1 FMR1, (CGG)n REPEAT EXPANSION Microsatellite Pathogenic 9972 GRCh37:
GRCh38:
2 FMR1 , FRAXA , LOC107032825 NM_002024.5(FMR1):c.-128_-126GGC(55_200) Microsatellite Pathogenic 623467 GRCh37: X:146993570-146993572
GRCh38: X:147912052-147912054

Expression for Fragile X-Associated Tremor/ataxia Syndrome

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

Pathways for Fragile X-Associated Tremor/ataxia Syndrome

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

# Super pathways Score Top Affiliating Genes
1 11.21 RBMX KHDRBS1 FMR1 DGCR8

GO Terms for Fragile X-Associated Tremor/ataxia Syndrome

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

# Name GO ID Score Top Affiliating Genes
1 ribonucleoprotein complex GO:1990904 9.26 RBMX HNRNPA2B1 FMR1 CELF1
2 cytoplasmic stress granule GO:0010494 8.92 MBNL1 FMR1 CELF1 C9orf72

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

# Name GO ID Score Top Affiliating Genes
1 RNA splicing GO:0008380 9.55 RBMX MBNL1 HNRNPA2B1 FMR1 CELF1
2 mRNA processing GO:0006397 9.43 RBMX MBNL1 KHDRBS1 HNRNPA2B1 FMR1 CELF1
3 embryo development ending in birth or egg hatching GO:0009792 9.4 FXN CELF1
4 negative regulation of mRNA splicing, via spliceosome GO:0048025 9.37 RBMX HNRNPA2B1
5 mRNA splice site selection GO:0006376 9.32 RBMX CELF1
6 primary miRNA processing GO:0031053 9.26 HNRNPA2B1 DGCR8
7 regulation of alternative mRNA splicing, via spliceosome GO:0000381 9.02 RBMX MBNL1 KHDRBS1 FMR1 CELF1

Molecular functions related to Fragile X-Associated Tremor/ataxia Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 identical protein binding GO:0042802 9.87 RBMX KHDRBS1 HNRNPA2B1 GRM5 FMR1 DGCR8
2 mRNA binding GO:0003729 9.46 RBMX KHDRBS1 FMR1 CELF1
3 poly(U) RNA binding GO:0008266 9.4 KHDRBS1 FMR1
4 translation initiation factor binding GO:0031369 9.37 FMR1 CELF1
5 RNA binding GO:0003723 9.28 RBMX PURA NOP56 MBNL1 KHDRBS1 HNRNPA2B1
6 translation repressor activity, mRNA regulatory element binding GO:0000900 9.26 PURA CELF1
7 mRNA 3'-UTR binding GO:0003730 9.26 MIR424 HNRNPA2B1 FMR1 CELF1

Sources for Fragile X-Associated 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-Apr-2021)
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 Tocris
70 UMLS
71 UMLS via Orphanet
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