FXS
MCID: FRG001
MIFTS: 76

Fragile X Syndrome (FXS) malady

Genetic diseases, Rare diseases, Neuronal diseases, Eye diseases, Endocrine diseases, Fetal diseases, Mental diseases categories
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Summaries for Fragile X Syndrome

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MedlinePlus:33 Fragile x syndrome is the most common form of inherited developmental disability. a problem with a specific gene causes the disease. normally, the gene makes a protein you need for brain development. but the problem causes a person to make little or none of the protein. this causes the symptoms of fragile x. people with only a small change in the gene might not show any signs of fragile x. people with bigger changes can have severe symptoms. these might include intelligence problems, ranging from learning disabilities to severe intellectual disabilities social and emotional problems, such as aggression in boys or shyness in girls speech and language problems, especially in boys a genetic blood test can diagnose fragile x. there is no cure. you can treat some symptoms with educational, behavioral, or physical therapy, and with medicines. getting treatment early can help. nih: national institute of child health and human development

MalaCards based summary: Fragile X Syndrome, also known as martin-bell syndrome, is related to fragile x-associated tremor/ataxia syndrome and prader-willi syndrome, and has symptoms including chronic/relapsing otitis, flat foot and macroorchidism/macrotestes. An important gene associated with Fragile X Syndrome is FMR1 (fragile X mental retardation 1), and among its related pathways are GABA signaling in brain and SIDS Susceptibility Pathways. The compounds hydrofluoric acid and hpaii have been mentioned in the context of this disorder. Affiliated tissues include testes, brain and eye, and related mouse phenotypes are endocrine/exocrine gland and reproductive system.

Disease Ontology:8 A neurodegenerative disease that is characterized by moderate to severe mental retardation, macroorchidism, and distinct facial features, including long face, large ears, and prominent jaw, and has material basis in a loss of fmr1 function.

Genetics Home Reference:21 Fragile X syndrome is a genetic condition that causes a range of developmental problems including learning disabilities and cognitive impairment. Usually, males are more severely affected by this disorder than females.

NIH Rare Diseases:42 Fragile x syndrome is a genetic condition involving changes in part of the x chromosome. this condition causes a range of developmental problems including learning disabilities and cognitive impairment. it is the most common form of inherited intellectual disability in males and a significant cause of intellectual disability in females.  fragile x syndrome is caused by a change in the fmr1 gene. fragile x syndrome is inherited in an x-linked dominant pattern. last updated: 6/23/2011

Wikipedia:65 Fragile X syndrome (FXS), also known as Martin?Bell syndrome, or Escalante\'s syndrome (more commonly... more...

Descriptions from OMIM:46 300624,309548

Aliases & Classifications for Fragile X Syndrome

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Sources:
8Disease Ontology, 9diseasecard, 65Wikipedia, 42NIH Rare Diseases, 21Genetics Home Reference, 46OMIM, 10DISEASES, 44Novoseek, 48Orphanet, 33MedlinePlus, 62UMLS, 20GeneTests, 22GTR, 27ICD9CM, 34MeSH, 39NCIt, 57SNOMED-CT, 35MESH via Orphanet, 26ICD10 via Orphanet, 63UMLS via Orphanet
See all sources

Fragile X Syndrome, Aliases & Descriptions:

Name: Fragile X Syndrome 8 9 65 42 21 46 10 44 48 33 62
Martin-Bell Syndrome 8 65 42 21 48 62
Fraxa Syndrome 65 42 21 44 48 62
Fraxe Syndrome 42 22 21 44 62
Fragile Xe Syndrome 42 20 22 21
Marker X Syndrome 8 65 42 21
Fra Syndrome 65 42 21 62
Fxs 65 42 21 48
X-Linked Mental Retardation and Macroorchidism 65 42 21
X-Linked Mental Retardation Associated with Fragile Site Fraxe 42 20
 
Mental Retardation, X-Linked, Fraxe Type 21 46
Fragile X Mental Retardation Syndrome 8 62
Fraxe Mental Retardation Syndrome 21 62
Fraxe Intellectual Disability 21 48
Mental Retardation, X-Linked, Associated with Fragile Site Fraxe 21
Intellectual Disability Associated with Fragile Site Fraxe 48
X-Linked Mental Retardation and Macro-Orchidism 42
Fragile Site, Folic Acid Type 42
Fraxe Intellectual Deficit 21
Frax Syndrome 48


Classifications:



Characteristics (Orphanet epidemiological data):

48
fragile x syndrome:
Inheritance: X-linked dominant; Prevalence: 1-5/10000; Age of onset: Childhood; Age of death: Normal
fraxe intellectual disability:
Inheritance: X-linked recessive; Prevalence: 1-9/1000000


External Ids:

Disease Ontology8 DOID:14261
ICD9CM27 759.83
SNOMED-CT57 390007001, 613003
NCIt39 C84717
MESH via Orphanet35 D005600
ICD10 via Orphanet26 Q99.2
UMLS via Orphanet63 C0016667, C0751156

Related Diseases for Fragile X Syndrome

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Diseases in the Fragile X Syndrome family:

Fragile X Syndrome Type 1 Fragile X Syndrome Type 2
Fragile X Syndrome Type 3

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

(show top 50)    (show all 77)
idRelated DiseaseScoreTop Affiliating Genes
1fragile x-associated tremor/ataxia syndrome31.5FMR1, FRAXA
2prader-willi syndrome30.8FMR1, MECP2, CYFIP1
3fragile x-associated primary ovarian insufficiency30.7FMR1, FRAXA
4myotonic dystrophy30.7AFF2, HTT, FMR1
5attention deficit hyperactivity disorder30.6MECP2, SLC6A4, FMR1
6mental retardation29.9CYFIP1, AFF2, PAH, FRAXA, FRAXE, MECP2
7autism spectrum disorder10.7
8down syndrome10.7
9ataxia10.5
10neuronitis10.5
11tremor10.5
12premature ovarian failure10.5
13learning disability10.4
14turner syndrome10.3
15williams syndrome10.3
16blindness10.3
17obsessive-compulsive disorder10.3SLC6A4
18pervasive developmental disorder10.3SLC6A4, MECP2
19cerebritis10.3
20fragile x syndrome type 110.3
21fragile x syndrome type 210.3
22fragile x syndrome type 310.3
23spinocerebellar ataxia10.2FMR1, HTT
24bone fracture10.2
25colorectal cancer10.2
26movement disease10.2FMR1, HTT
27asperger syndrome10.2SLC6A4, MECP2
28autistic disorder10.1MECP2, SLC6A4, FMR1
29alzheimer's disease10.1
30duchenne muscular dystrophy10.1
31hepatitis10.1
32huntington's disease10.1
33obesity10.1
34angelman syndrome10.1
35williams-beuren syndrome10.1
36cherubism10.1
37status epilepticus10.1
38werner syndrome10.1
39diabetes insipidus10.1
40myotonic dystrophy type 110.1
41congenital nystagmus10.1
42infertility10.1
43velocardiofacial syndrome10.1
44achondroplasia10.1
45friedreich ataxia10.1
46neurofibromatosis10.1
47fetal alcohol syndrome10.1
48nephrogenic diabetes insipidus10.1
49batten disease10.1
50premature menopause10.1

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



Diseases related to fragile x syndrome

Symptoms for Fragile X Syndrome

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Symptoms by clinical synopsis from OMIM:

300624

Clinical features from OMIM:

300624,309548

Symptoms:

48 (show all 27)
  • chronic/relapsing otitis
  • flat foot
  • macroorchidism/macrotestes
  • speech troubles/aphasia/dysphasia/echolalia/mutism/logorrhea/dysprosodia
  • intellectual deficit/mental/psychomotor retardation/learning disability
  • hyperextensible joints/articular hyperlaxity
  • x-linked dominant inheritance
  • fragile chromosome x site
  • macrocephaly/macrocrania/megalocephaly/megacephaly
  • frontal bossing/prominent forehead
  • narrow face
  • long face
  • prognathism/prognathia
  • nasal congestion/sinusitis/rhinitis/rhinorrhea
  • prominent/bat ears
  • gastroesophageal reflux/pyrosis/esophagitis/hiatal hernia/gastroparesia
  • hypotonia
  • hyperactivity/attention deficit
  • strabismus/squint
  • mitral valve prolapse/incompetence/insufficiency/regurgitation/ring anomaly
  • aortic root dilatation/dilation/aneurysm
  • cortical atrophy without hydrocephaly/cerebral hemiatrophy/subcortical atrophy
  • seizures/epilepsy/absences/spasms/status epilepticus
  • autism/autistic disoders
  • humour troubles/anxiety/depression/apathy/euphoria/irritability
  • psychosis/schizophrenia/maniac disorder
  • auto-aggressivity/auto-mutilation

HPO human phenotypes related to Fragile X Syndrome:

(show all 56)
id Description Frequency HPO Source Accession
1 macroorchidism hallmark (90%) HP:0000053
2 otitis media hallmark (90%) HP:0000388
3 joint hypermobility hallmark (90%) HP:0001382
4 pes planus hallmark (90%) HP:0001763
5 neurological speech impairment hallmark (90%) HP:0002167
6 cognitive impairment hallmark (90%) HP:0100543
7 intellectual disability, moderate typical (50%) HP:0002342
8 sinusitis typical (50%) HP:0000246
9 macrocephaly typical (50%) HP:0000256
10 narrow face typical (50%) HP:0000275
11 long face typical (50%) HP:0000276
12 mandibular prognathia typical (50%) HP:0000303
13 abnormality of the pinna typical (50%) HP:0000377
14 muscular hypotonia typical (50%) HP:0001252
15 frontal bossing typical (50%) HP:0002007
16 attention deficit hyperactivity disorder typical (50%) HP:0007018
17 strabismus occasional (7.5%) HP:0000486
18 autism occasional (7.5%) HP:0000717
19 seizures occasional (7.5%) HP:0001250
20 abnormality of the mitral valve occasional (7.5%) HP:0001633
21 cerebral cortical atrophy occasional (7.5%) HP:0002120
22 dilatation of the ascending aorta occasional (7.5%) HP:0005111
23 self-injurious behavior occasional (7.5%) HP:0100716
24 macrocephaly HP:0000256
25 long face HP:0000276
26 coarse facial features HP:0000280
27 mandibular prognathia HP:0000303
28 macrotia HP:0000400
29 autism HP:0000717
30 hyperactivity HP:0000752
31 pectus excavatum HP:0000767
32 poor eye contact HP:0000817
33 seizures HP:0001250
34 joint laxity HP:0001388
35 x-linked dominant inheritance HP:0001423
36 mitral valve prolapse HP:0001634
37 pes planus HP:0001763
38 large forehead HP:0002003
39 macroorchidism, postpubertal HP:0002050
40 abnormal head movements HP:0002457
41 scoliosis HP:0002650
42 folate-dependent fragile site at xq28 HP:0003564
43 incomplete penetrance HP:0003829
44 periventricular gray matter heterotopia HP:0007165
45 congenital macroorchidism HP:0008640
46 epicanthus HP:0000286
47 prominent nasal bridge HP:0000426
48 agitation HP:0000713
49 aggressive behavior HP:0000718
50 obsessive-compulsive behavior HP:0000722
51 delayed speech and language development HP:0000750
52 hyperactivity HP:0000752
53 intellectual disability HP:0001249
54 x-linked recessive inheritance HP:0001419
55 abnormality of metabolism/homeostasis HP:0001939
56 impulsivity HP:0100710

Drugs & Therapeutics for Fragile X Syndrome

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Drug clinical trials:

Search ClinicalTrials for Fragile X Syndrome

Search NIH Clinical Center for Fragile X Syndrome

Genetic Tests for Fragile X Syndrome

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Genetic tests related to Fragile X Syndrome:

id Genetic test Affiliating Genes
1 X-Linked Mental Retardation Associated with Fragile Site Fraxe20 AFF2
2 Fragile X Syndrome20 22 FMR1
3 Fraxe22

Anatomical Context for Fragile X Syndrome

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MalaCards organs/tissues related to Fragile X Syndrome:

32
Testes, Brain, Eye, Amygdala, Cortex, Cerebellum, Heart, Skin, Prefrontal cortex, Temporal lobe, Thalamus

Animal Models for Fragile X Syndrome or affiliated genes

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MGI Mouse Phenotypes related to Fragile X Syndrome:

36
idDescriptionMGI Source AccessionScoreTop Affiliating Genes
1MP:00053797.8MECP2, HTT, FMR1, NR1H4, GRM5, FXR1
2MP:00053897.0MECP2, HTT, MAP1B, FMR1, GRM5, FXR1
3MP:00107687.0AFF2, FXR1, SLC6A4, NR1H4, MAP1B, HTT
4MP:00107716.9FXR2, AFF2, PAH, MECP2, HTT, MAP1B
5MP:00053786.7SLC6A4, AFF2, PAH, FXR1, GRM5, NR1H4
6MP:00036316.5HTT, MECP2, PAH, AFF2, MAP1B, FMR1
7MP:00053866.3FXR2, FXR1, SLC6A4, GRM5, NR1H4, FMR1

Publications for Fragile X Syndrome

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Articles related to Fragile X Syndrome:

(show top 50)    (show all 695)
idTitleAuthorsYear
1
Modulation of the GABAergic pathway for the treatment of fragile X syndrome. (25258535)
2014
2
The contribution of inhibitory interneurons to circuit dysfunction in Fragile X Syndrome. (25202236)
2014
3
A family with fragile X syndrome, Duchenne muscular dystrophy and ichthyosis transmitted by an asymptomatic carrier. (23574351)
2013
4
Electrocortical changes associated with minocycline treatment in fragile X syndrome. (23981511)
2013
5
Physiological arousal in autism and fragile x syndrome: group comparisons and links with pragmatic language. (24432860)
2013
6
Implementation of a markerless motion analysis method to quantify hyperkinesis in males with fragile X syndrome. (24252602)
2013
7
A neurodevelopmental perspective on the acquisition of nonverbal cognitive skills in adolescents with fragile X syndrome. (24138215)
2013
8
Visual-spatial learning impairments are associated with hippocampal PSD-95 protein dysregulation in a mouse model of fragile X syndrome. (24323121)
2013
9
FXTAS in an unmethylated mosaic male with fragile X syndrome from Chile. (24028275)
2013
10
Lithium ameliorates open-field and elevated plus maze behaviors, and brain phospho-glycogen synthase kinase 3-beta expression in fragile X syndrome model mice. (24141459)
2013
11
Males but not females show differences in calbindin immunoreactivity in the dorsal thalamus of the mouse model of fragile X syndrome. (22886886)
2013
12
The role of glycogen synthase kinase-3 signaling in neurodevelopment and fragile X syndrome. (23071871)
2012
13
Genetic removal of p70 S6 kinase 1 corrects molecular, synaptic, and behavioral phenotypes in fragile X syndrome mice. (23083736)
2012
14
Behavioral phenotype of fragile X syndrome in adolescence and adulthood. (22264109)
2012
15
Behavioral features of Williams Beuren syndrome compared to Fragile X syndrome and subjects with intellectual disability without defined etiology. (21211940)
2011
16
Predisposition to epilepsy in fragile X syndrome: does the Val66Met polymorphism in the BDNF gene play a role? (21890420)
2011
17
Amygdala regulation of fear and emotionality in fragile X syndrome. (21893939)
2011
18
The psychiatric presentation of fragile x: evolution of the diagnosis and treatment of the psychiatric comorbidities of fragile X syndrome. (21893938)
2011
19
Targeted treatments for fragile X syndrome. (21484200)
2011
20
ACOG Committee Opinion No. 469: Carrier screening for fragile X syndrome. (20859177)
2010
21
Associating neural alterations and genotype in autism and fragile x syndrome: incorporating perceptual phenotypes in causal modeling. (20872060)
2010
22
Side effects of minocycline treatment in patients with fragile X syndrome and exploration of outcome measures. (20687826)
2010
23
Using perceptual signatures to define and dissociate condition-specific neural etiology: autism and fragile X syndrome as model conditions. (20886276)
2010
24
Characterization and reversal of synaptic defects in the amygdala in a mouse model of fragile X syndrome. (20534533)
2010
25
Fragile X syndrome and associated disorders. (21189809)
2010
26
Qualitative assessment of FMR1 (CGG)n triplet repeat status in normal, intermediate, premutation, full mutation, and mosaic carriers in both sexes: implications for fragile X syndrome carrier and newborn screening. (20168238)
2010
27
The role of DNA damage response pathways in chromosome fragility in Fragile X syndrome. (19465392)
2009
28
A distinct DNA-methylation boundary in the 5'- upstream sequence of the FMR1 promoter binds nuclear proteins and is lost in fragile X syndrome. (19853235)
2009
29
Mutation spectra in fragile X syndrome induced by deletions of CGG*CCG repeats. (18957433)
2009
30
A review of mathematical learning disabilities in children with fragile X syndrome. (19213014)
2009
31
Molecular analysis of Fragile X syndrome. (19806593)
2009
32
The efficacy of melatonin for sleep problems in children with autism, fragile X syndrome, or autism and fragile X syndrome. (19968048)
2009
33
Brief report: aggression and stereotypic behavior in males with fragile X syndrome--moderating secondary genes in a "single gene" disorder. (17340199)
2008
34
Secondary medical diagnosis in fragile X syndrome with and without autism spectrum disorder. (18627038)
2008
35
Morphometric spatial patterns differentiating boys with fragile X syndrome, typically developing boys, and developmentally delayed boys aged 1 to 3 years. (18762595)
2008
36
The Epigenetics of Fragile X Syndrome. (18371387)
2007
37
Fragile-X syndrome and fragile X-associated tremor/ataxia syndrome: two faces of FMR1. (17166801)
2007
38
Mathematics learning disability in girls with Turner syndrome or fragile X syndrome. (16500739)
2006
39
The fragile X syndrome: exploring its molecular basis and seeking a treatment. (16626504)
2006
40
Cognitive aspects in girls with fragile X syndrome]. (15011155)
2004
41
A step-wise diagnosis of fragile X syndrome in Taiwan. (15335113)
2004
42
Histone modifications depict an aberrantly heterochromatinized FMR1 gene in fragile x syndrome. (12232854)
2002
43
Diagnosis of fragile X syndrome]. (12447811)
2001
44
Sequence-specific RNA binding by a Nova KH domain: implications for paraneoplastic disease and the fragile X syndrome. (10676814)
2000
45
Preimplantation diagnosis for fragile X syndrome based on the detection of the non-expanded paternal and maternal CGG. (10660959)
1999
46
Fragile X syndrome is less common than previously estimated. (9032640)
1997
47
An atypical case of fragile X syndrome caused by a deletion that includes the FMR1 gene. (7726157)
1995
48
Rett-like syndrome in fragile X syndrome. (8588847)
1995
49
Molecular predictors of cognitive involvement in female carriers of fragile X syndrome. (8301764)
1994
50
Cytogenetic studies in fragile X syndrome]. (1437821)
1992

Variations for Fragile X Syndrome

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UniProtKB/Swiss-Prot genetic disease variations for Fragile X Syndrome:

64
id Symbol AA change Variation ID SNP ID
1FMR1p.Ile304AsnVAR_005234

Clinvar genetic disease variations for Fragile X Syndrome:

6
id Gene Name Type Significance SNP ID Assembly Location
1AFF2AFF2, 121- to 145-KB DELdeletionPathogenic
2FMR1FMR1, SER27TERsingle nucleotide variantPathogenic
3FMR1NM_002024.5(FMR1): c.911T> A (p.Ile304Asn)single nucleotide variantPathogenicrs121434622GRCh37Chr X, 147018053: 147018053
4FMR1FMR1, 1-BP DEL, 373AdeletionPathogenic
5FMR1FMR1, IVS2AS1, G-T, -1 AND G-A, +1single nucleotide variantPathogenic
6FMR1FMR1, (CGG)n EXPANSIONNT expansionPathogenic

Expression for genes affiliated with Fragile X Syndrome

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Expression patterns in normal tissues for genes affiliated with Fragile X Syndrome

Search GEO for disease gene expression data for Fragile X Syndrome.

Pathways for genes affiliated with Fragile X Syndrome

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Pathways related to Fragile X Syndrome according to GeneCards/GeneDecks:

idSuper pathways (with members indented)ScoreTop Affiliating Genes
1
Show member pathways
9.8GRM5, MECP2
29.4SLC6A4, MECP2, PAH
39.3FMR1, FXR1, FXR2
48.7FXR2, FXR1, FMR1, HTT, MECP2
58.7CYFIP1, FMR1, FXR1, FXR2

Compounds for genes affiliated with Fragile X Syndrome

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Compounds related to Fragile X Syndrome according to GeneCards/GeneDecks:

(show all 11)
idCompoundScoreTop Affiliating Genes
1hydrofluoric acid449.9SLC6A4, GRM5
2hpaii449.7MECP2, FMR1
3folate449.6MECP2, FMR1, AFF2, PAH
4lithium44 50 24 1112.2SLC6A4, FMR1, MAP1B
5testosterone44 61 24 1112.1SLC6A4, MECP2, HTT, FMR1, NR1H4
6dopamine44 28 24 1112.0PAH, HTT, GRM5, SLC6A4
7arginine448.9PAH, MECP2, FMR1, NR1H4, SLC6A4
8glutamate448.8SLC6A4, GRM5, FMR1, HTT, MECP2
9nmda44 289.7GRM5, SLC6A4, MAP1B, HTT
10gaba448.6SLC6A4, GRM5, FMR1, MAP1B, MECP2
11oligonucleotide448.6HTT, FMR1, MAP1B, MECP2, PAH

GO Terms for genes affiliated with Fragile X Syndrome

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Cellular components related to Fragile X Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1dendritic shaftGO:0431989.9FMR1, GRM5
2mRNA cap binding complexGO:0058459.6FMR1, CYFIP1
3dendritic spineGO:0431979.1GRM5, FMR1, MAP1B
4synapseGO:0452028.5MAP1B, FMR1, CYFIP1

Biological processes related to Fragile X Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1visual learningGO:0085429.9HTT, MECP2
2social behaviorGO:0351769.4SLC6A4, HTT, MECP2
3dendrite developmentGO:0163589.1MAP1B, MECP2
4axon extensionGO:0486758.9MAP1B, CYFIP1

Molecular functions related to Fragile X Syndrome according to GeneCards/GeneDecks:

idNameGO IDScoreTop Affiliating Genes
1G-quadruplex RNA bindingGO:0021519.7FXR1, AFF2

Products for genes affiliated with Fragile X Syndrome

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Sources for Fragile X Syndrome

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3CDC
13ExPASy
14FMA
22GTR
23HGMD
24HMDB
25ICD10
26ICD10 via Orphanet
27ICD9CM
28IUPHAR
29KEGG
34MeSH
35MESH via Orphanet
36MGI
39NCIt
40NDF-RT
43NINDS
44Novoseek
46OMIM
47OMIM via Orphanet
51PubMed
52QIAGEN
58SNOMED-CT via Orphanet
62UMLS
63UMLS via Orphanet