FXS
MCID: FRG001
MIFTS: 69

Fragile X Syndrome (FXS)

Categories: Endocrine diseases, Eye diseases, Fetal diseases, Genetic diseases, Neuronal diseases, Rare diseases, Reproductive diseases

Aliases & Classifications for Fragile X Syndrome

MalaCards integrated aliases for Fragile X Syndrome:

Name: Fragile X Syndrome 56 12 74 52 25 58 73 36 29 13 54 6 42 3 43 15 71
Martin-Bell Syndrome 56 12 52 25 58 73
Fxs 56 52 25 58 73 3
X-Linked Mental Retardation and Macroorchidism 56 74 52 25 73
Marker X Syndrome 56 12 52 25 73
Fraxa Syndrome 52 25 58 54 71
Fraxe Syndrome 52 25 54 71
Mental Retardation, X-Linked, Fraxe Type 25 29 39
Fragile X Mental Retardation Syndrome 56 12 73
Mental Retardation, X-Linked, Associated with Marxq28 56 73
Fragile Xe Syndrome 52 25
Fra Syndrome 52 25
Fraxe 29 6
Mental Retardation, X-Linked, Associated with Fragile Site Fraxe 25
X-Linked Mental Retardation Associated with Fragile Site Fraxe 52
Symptomatic Form of Fragile X Syndrome in Female Carrier 58
Fraxe Mental Retardation Syndrome 25
Fragile Site, Folic Acid Type 52
Fraxe Intellectual Disability 25
Fraxe Intellectual Deficit 25
Syndrome, Fragile-X 39
Frax Syndrome 58

Characteristics:

Orphanet epidemiological data:

58
fragile x syndrome
Inheritance: X-linked dominant; Prevalence: 1-5/10000 (Worldwide),1-5/10000 (Europe),1-9/100000 (United States),1-9/100000 (France),1-5/10000 (Spain),1-5/10000 (Canada); Age of onset: Childhood,Infancy,Neonatal; Age of death: normal life expectancy;
symptomatic form of fragile x syndrome in female carrier
Inheritance: X-linked dominant; Age of onset: Childhood,Infancy,Neonatal; Age of death: normal life expectancy;

OMIM:

56
Miscellaneous:
incomplete penetrance
50% of females have learning disability or mild mental retardation
prevalence approximately 1 in 4,000 males
most cases (98%) caused by expanded trinucleotide repeat (cgg)n in the fmr1 gene
repeat is unstable if > 52 repeats
symptomatic if > 200 repeats
some boys with premutations (55 to 200 repeats) may show milder features, including autistic features

Inheritance:
x-linked dominant


HPO:

31
fragile x syndrome:
Onset and clinical course incomplete penetrance
Inheritance x-linked dominant inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Rare eye diseases
Rare gynaecological and obstetric diseases
Rare endocrine diseases
Developmental anomalies during embryogenesis


Summaries for Fragile X Syndrome

Genetics Home Reference : 25 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. Affected individuals usually have delayed development of speech and language by age 2. Most males with fragile X syndrome have mild to moderate intellectual disability, while about one-third of affected females are intellectually disabled. Children with fragile X syndrome may also have anxiety and hyperactive behavior such as fidgeting or impulsive actions. They may have attention deficit disorder (ADD), which includes an impaired ability to maintain attention and difficulty focusing on specific tasks. About one-third of individuals with fragile X syndrome have features of autism spectrum disorder that affect communication and social interaction. Seizures occur in about 15 percent of males and about 5 percent of females with fragile X syndrome. Most males and about half of females with fragile X syndrome have characteristic physical features that become more apparent with age. These features include a long and narrow face, large ears, a prominent jaw and forehead, unusually flexible fingers, flat feet, and in males, enlarged testicles (macroorchidism) after puberty.

MalaCards based summary : Fragile X Syndrome, also known as martin-bell syndrome, is related to fragile x tremor/ataxia syndrome and fmr1 disorders, and has symptoms including seizures and agitation. An important gene associated with Fragile X Syndrome is FMR1 (FMRP Translational Regulator 1), and among its related pathways/superpathways are RNA transport and Neuroscience. The drugs Riluzole and Dopamine have been mentioned in the context of this disorder. Affiliated tissues include brain, testes and cortex, and related phenotypes are neurological speech impairment and chronic otitis media

Disease Ontology : 12 A X-linked dominant 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 X-linked inheritance and a loss of FMR1 function.

NIH Rare Diseases : 52 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. Other signs and symptoms may include symptoms of autism spectrum disorders , seizures , and characteristic physical features. Fragile X syndrome is caused by a change (mutation ) in the FMR1 gene and is inherited in an X-linked dominant manner. There is no cure yet and treatment is based on the symptoms present in the person. Early physical and education therapy is recommended.

OMIM : 56 Fragile X syndrome is characterized by moderate to severe mental retardation, macroorchidism, and distinct facial features, including long face, large ears, and prominent jaw. In most cases, the disorder is caused by the unstable expansion of a CGG repeat in the FMR1 gene and abnormal methylation, which results in suppression of FMR1 transcription and decreased protein levels in the brain (Devys et al., 1993). (300624)

MedlinePlus : 42 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

CDC : 3 Fragile X syndrome (FXS) is one of the most common causes of inherited intellectual disability. CDC is working to learn more about fragile X syndrome and fragile X-associated disorders to improve the health and well-being of people with these conditions.

KEGG : 36 Fragile X syndrome (FXS) is a cognitive disorder caused by silencing of the fragile X mental retardation 1 gene (FMR1). Absence of the associated protein FMRP leads to the dysregulation of many genes creating a phenotype of ADHD, anxiety, epilepsy and autism.There are also several physical features commonly associated with FXS, including elongated faces, prominent ears, and macroorchidism. The most prevalent genetic aberration at the FMR1 locus arises from a noncoding CGG repeat in the 5'untranslated region.

UniProtKB/Swiss-Prot : 73 Fragile X syndrome: A X-linked dominant disease characterized by moderate to severe mental retardation, macroorchidism (enlargement of the testicles), large ears, prominent jaw, and high-pitched, jocular speech. The defect in most patients results from an amplification of a CGG repeat region in the FMR1 gene and abnormal methylation.

Wikipedia : 74 Fragile X syndrome (FXS) is a genetic disorder. Symptoms often include mild to moderate intellectual... more...

Related Diseases for Fragile X Syndrome

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 Suite gene sharing:

(show top 50) (show all 374)
# Related Disease Score Top Affiliating Genes
1 fragile x tremor/ataxia syndrome 34.0 LOC108684022 FMR1-AS1 FMR1
2 fmr1 disorders 33.5 LOC108684022 FMR1
3 autism spectrum disorder 32.3 SLC6A4 MECP2 FMR1 BDNF AFF2
4 autism 32.2 SLC6A4 MECP2 MAP1B GRM5 GRIA1 FXR2
5 fragile x-associated tremor/ataxia syndrome 32.0 LOC108684022 GRM5 FMR1-AS1 FMR1
6 attention deficit-hyperactivity disorder 31.6 SLC6A4 MECP2 MAP1B GRM5 FMR1 BDNF
7 pervasive developmental disorder 31.5 SLC6A4 MECP2 LOC108684022 GRM5 GRIA1 FMR1
8 rett syndrome 31.3 MECP2 GRM5 GRIA1 BDNF
9 prader-willi syndrome 31.3 MECP2 FMR1 CYFIP1 BDNF
10 focal epilepsy 31.1 MECP2 GRM5 GRM1 GRIA1 BDNF
11 echolalia 31.1 MECP2 FMR1
12 migraine with or without aura 1 30.9 SLC6A4 GRM5 FMR1 BDNF
13 status epilepticus 30.9 GRM5 GRIA1 BDNF
14 fibromyalgia 30.9 SLC6A4 SERPINA1 FMR1 BDNF
15 asperger syndrome 30.9 SLC6A4 MECP2 BDNF
16 bipolar disorder 30.8 SLC6A4 MECP2 GRM5 GRM1 GRIA1 BDNF
17 temporal lobe epilepsy 30.7 GRM5 GRM1 BDNF
18 mental depression 30.7 SLC6A4 GRIA1 BDNF
19 depression 30.7 SLC6A4 GRM1 GRIA1 BDNF
20 disease of mental health 30.7 SLC6A4 MECP2 GRM5 GRIA1 FMR1 BDNF
21 mental retardation, x-linked, associated with fragile site fraxe 30.7 SERPINA1 AFF2
22 psychotic disorder 30.7 SLC6A4 GRM5 GRM1 GRIA1 BDNF
23 central nervous system disease 30.6 SLC6A4 GRM5 GRM1 BDNF
24 atypical autism 30.0 MECP2 FMR1
25 fragile x syndrome type 1 12.3
26 fragile x syndrome type 2 12.3
27 fragile x syndrome type 3 12.3
28 factor x deficiency 11.7
29 premature ovarian failure 1 11.7
30 cherubism 11.5
31 childhood apraxia of speech 11.2
32 alacrima, achalasia, and mental retardation syndrome 11.1
33 osteoporosis 11.0
34 bone mineral density quantitative trait locus 8 11.0
35 bone mineral density quantitative trait locus 15 11.0
36 down syndrome 10.8
37 x-linked hereditary ataxia 10.7 GRM5 FXR2 FMR1-AS1 FMR1
38 lubs x-linked mental retardation syndrome 10.7 MECP2 FMR1 BDNF
39 schizophrenia 5 10.7 SLC6A4 BDNF
40 phobic disorder 10.7 SLC6A4 FMR1 BDNF
41 chromosome 15q11.2 deletion syndrome 10.7 FMR1 CYFIP1
42 retrograde amnesia 10.7 SLC6A4 GRIA1 BDNF
43 chromosomal disease 10.7 MECP2 FMR1 CYFIP1 BDNF
44 toxic encephalopathy 10.7 SLC6A4 GRIA1 BDNF
45 atypical depressive disorder 10.7 SLC6A4 BDNF
46 central hypoventilation syndrome, congenital 10.7 SLC6A4 MECP2 BDNF
47 anterograde amnesia 10.7 GRM5 BDNF
48 alcohol use disorder 10.7 SLC6A4 GRM5 BDNF
49 ataxia and polyneuropathy, adult-onset 10.6
50 learning disability 10.6

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



Diseases related to Fragile X Syndrome

Symptoms & Phenotypes for Fragile X Syndrome

Human phenotypes related to Fragile X Syndrome:

58 31 (show top 50) (show all 57)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 neurological speech impairment 58 31 hallmark (90%) Very frequent (99-80%) HP:0002167
2 chronic otitis media 58 31 hallmark (90%) Very frequent (99-80%) HP:0000389
3 macroorchidism 58 31 hallmark (90%) Very frequent (99-80%) HP:0000053
4 pes planus 58 31 hallmark (90%) Very frequent (99-80%) HP:0001763
5 intellectual disability, moderate 58 31 frequent (33%) Very frequent (99-80%) HP:0002342
6 joint laxity 58 31 hallmark (90%) Very frequent (99-80%) HP:0001388
7 folate-dependent fragile site at xq28 58 31 hallmark (90%) Very frequent (99-80%) HP:0003564
8 macrocephaly 58 31 occasional (7.5%) Frequent (79-30%) HP:0000256
9 frontal bossing 58 31 frequent (33%) Frequent (79-30%) HP:0002007
10 muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0001252
11 mandibular prognathia 58 31 frequent (33%) Frequent (79-30%) HP:0000303
12 gastroesophageal reflux 58 31 frequent (33%) Frequent (79-30%) HP:0002020
13 protruding ear 58 31 frequent (33%) Frequent (79-30%) HP:0000411
14 sinusitis 58 31 frequent (33%) Frequent (79-30%) HP:0000246
15 attention deficit hyperactivity disorder 58 31 frequent (33%) Frequent (79-30%) HP:0007018
16 narrow face 58 31 frequent (33%) Frequent (79-30%) HP:0000275
17 long face 58 31 frequent (33%) Frequent (79-30%) HP:0000276
18 large forehead 58 31 frequent (33%) Frequent (79-30%) HP:0002003
19 intellectual disability 31 frequent (33%) HP:0001249
20 delayed speech and language development 31 frequent (33%) HP:0000750
21 thick vermilion border 31 frequent (33%) HP:0012471
22 short stature 31 frequent (33%) HP:0004322
23 intrauterine growth retardation 31 frequent (33%) HP:0001511
24 hyperactivity 31 frequent (33%) HP:0000752
25 epicanthus 31 frequent (33%) HP:0000286
26 specific learning disability 31 frequent (33%) HP:0001328
27 prominent nasal bridge 31 frequent (33%) HP:0000426
28 aggressive behavior 31 frequent (33%) HP:0000718
29 obsessive-compulsive behavior 31 frequent (33%) HP:0000722
30 agitation 31 frequent (33%) HP:0000713
31 clumsiness 31 frequent (33%) HP:0002312
32 hoarse voice 31 frequent (33%) HP:0001609
33 autistic behavior 31 frequent (33%) HP:0000729
34 impulsivity 31 frequent (33%) HP:0100710
35 recurrent hand flapping 31 frequent (33%) HP:0100023
36 prominent ear helix 31 frequent (33%) HP:0009904
37 seizures 58 31 occasional (7.5%) Occasional (29-5%) HP:0001250
38 self-injurious behavior 58 31 occasional (7.5%) Occasional (29-5%) HP:0100716
39 cerebral cortical atrophy 58 31 occasional (7.5%) Occasional (29-5%) HP:0002120
40 strabismus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000486
41 autism 58 31 occasional (7.5%) Occasional (29-5%) HP:0000717
42 anxiety 58 31 occasional (7.5%) Occasional (29-5%) HP:0000739
43 mitral valve prolapse 58 31 occasional (7.5%) Occasional (29-5%) HP:0001634
44 clinodactyly of the 5th finger 31 occasional (7.5%) HP:0004209
45 stereotypical body rocking 31 occasional (7.5%) HP:0012172
46 ascending tubular aorta aneurysm 31 occasional (7.5%) HP:0004970
47 pectus excavatum 31 HP:0000767
48 scoliosis 31 HP:0002650
49 coarse facial features 31 HP:0000280
50 macrotia 31 HP:0000400

Symptoms via clinical synopsis from OMIM:

56
Head And Neck Head:
macrocephaly

Neurologic Central Nervous System:
seizures
abnormal head movements
periventricular heterotopia
mental retardation (moderate to severe in males)

Skeletal Feet:
pes planus

Cardiovascular Heart:
mitral valve prolapse

Laboratory Abnormalities:
folate-dependent fragile site at xq28

Genitourinary External Genitalia Male:
macroorchidism, postpubertal
congenital macroorchidism (in some patients)

Chest Ribs Sternum Clavicles And Scapulae:
pectus excavatum

Skeletal Spine:
scoliosis

Skeletal Limbs:
joint laxity

Head And Neck Face:
long face
large forehead
coarse facies
prominent jaw

Neurologic Behavioral Psychiatric Manifestations:
poor eye contact
autistic features
hyperactive behavior

Head And Neck Ears:
large ears

Clinical features from OMIM:

300624

UMLS symptoms related to Fragile X Syndrome:


seizures, agitation

MGI Mouse Phenotypes related to Fragile X Syndrome:

45
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.73 BDNF CYFIP1 FMR1 FXR1 FXR2 GRIA1
2 integument MP:0010771 9.32 BDNF FMR1 FXR2 GRIA1 GRM1 GRM5

Drugs & Therapeutics for Fragile X Syndrome

Drugs for Fragile X Syndrome (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show top 50) (show all 113)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Riluzole Approved, Investigational Phase 4 1744-22-5 5070
2
Dopamine Approved Phase 4 51-61-6, 62-31-7 681
3
Methylphenidate Approved, Investigational Phase 4 113-45-1 4158
4
Risperidone Approved, Investigational Phase 4 106266-06-2 5073
5 Excitatory Amino Acid Antagonists Phase 4
6 Excitatory Amino Acids Phase 4
7 Neurotransmitter Agents Phase 4
8 Central Nervous System Depressants Phase 4
9 Central Nervous System Stimulants Phase 4
10 Dopamine Agents Phase 4
11 Antipsychotic Agents Phase 4
12 Dopamine Antagonists Phase 4
13 Tranquilizing Agents Phase 4
14 Psychotropic Drugs Phase 4
15 Serotonin Agents Phase 4
16 Dopamine Uptake Inhibitors Phase 4
17 Serotonin Antagonists Phase 4
18
Serotonin Investigational, Nutraceutical Phase 4 50-67-9 5202
19
Baclofen Approved Phase 3 1134-47-0 2284
20
Metformin Approved Phase 2, Phase 3 657-24-9 4091 14219
21 Pharmaceutical Solutions Phase 3
22 Anticonvulsants Phase 2, Phase 3
23 Epidiolex Phase 2, Phase 3
24 Hypoglycemic Agents Phase 2, Phase 3
25
Aripiprazole Approved, Investigational Phase 2 129722-12-9 60795
26 Strawberry Approved Phase 2
27
Donepezil Approved Phase 2 120014-06-4 3152
28
Tocopherol Approved, Investigational Phase 2 1406-66-2, 54-28-4 14986
29
Oxytocin Approved, Vet_approved Phase 2 50-56-6 53477758 439302
30
Sertraline Approved Phase 2 79617-96-2 68617
31
Adenosine Approved, Investigational Phase 2 58-61-7 60961
32
leucovorin Approved Phase 2 58-05-9 6006 143
33
Lovastatin Approved, Investigational Phase 2 75330-75-5 53232
34
Ethanol Approved Phase 2 64-17-5 702
35
Acamprosate Approved, Investigational Phase 2 77337-76-9 71158
36
Minocycline Approved, Investigational Phase 2 10118-90-8 5281021
37
Glutamic acid Approved, Nutraceutical Phase 2 56-86-0 33032
38
Pyridoxine Approved, Investigational, Nutraceutical, Vet_approved Phase 2 65-23-6 1054
39
Folic acid Approved, Nutraceutical, Vet_approved Phase 2 59-30-3 6037
40
Vitamin E Approved, Nutraceutical, Vet_approved Phase 2 59-02-9 14985
41
Vitamin C Approved, Nutraceutical Phase 2 50-81-7 5785 54670067
42
Epigallocatechin Experimental, Investigational Phase 2 970-74-1 72277
43
Epigallocatechin gallate Investigational Phase 2 989-51-5 65064
44 Tocotrienol Investigational Phase 2 6829-55-6
45
Gaboxadol Investigational Phase 2 64603-91-4 3448
46 Serotonin Receptor Agonists Phase 2
47 Dopamine agonists Phase 2
48 Antidepressive Agents Phase 2
49 Dopamine D2 Receptor Antagonists Phase 2
50 Serotonin 5-HT1 Receptor Agonists Phase 2

Interventional clinical trials:

(show top 50) (show all 86)
# Name Status NCT ID Phase Drugs
1 Combining Lovastatin and a Parent-Implemented Language Intervention in a Multimodal Treatment for Fragile X Syndrome Completed NCT02642653 Phase 4 Lovastatin
2 Riluzole in Fragile X Syndrome: A Pilot Study Incorporating Biomarker Assay Completed NCT00895752 Phase 4 Riluzole
3 The Psychiatric and Cognitive Phenotypes in Velocardiofacial Syndrome (VCFS), Williams Syndrome (WS)and Fragile X Syndrome Characterization, Treatment and Examining the Connection to Developmental and Molecular Factors Recruiting NCT00768820 Phase 4 methylphenidate, fluoxetin, risperidone
4 Clinical Trials Phase III, Double Blind, Crossover to Asses the Safety and Efficacy of Vitamin C and Vitamin E in Combination Versus Placebo for Treating Cognitive and Behavior Disorder in Children With Fragile X Syndrome Unknown status NCT02942498 Phase 3 Vitamin C 10mg/Kg Vitamin E 10 mg/Kg;Placebo
5 A Randomized, Double-Blind, Placebo-Controlled Study of the Efficacy, Safety, and Tolerability of STX209 (Arbaclofen) Administered for the Treatment of Social Function in Adolescents and Adults With Fragile X Syndrome Completed NCT01282268 Phase 3 arbaclofen;placebo
6 A Randomized, Double-Blind, Placebo-Controlled, Fixed-Dose Study of the Efficacy, Safety, and Tolerability of STX209 (Arbaclofen) Administered for the Treatment of Social Function in Children With Fragile X Syndrome Completed NCT01325220 Phase 3 arbaclofen;arbaclofen;arbaclofen;Placebo
7 A Randomized, Double-Blind, Placebo-Controlled Multiple-Center, Efficacy and Safety Study of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With Fragile X Syndrome Recruiting NCT03614663 Phase 2, Phase 3 ZYN002 - CBD Transdermal Gel
8 A Double-Blind, Placebo-Controlled Trial of Metformin in Individuals With Fragile X Syndrome Recruiting NCT03479476 Phase 2, Phase 3 Placebo Medication;Metformin
9 An Open-Label Extension Study to Assess the Long-Term Safety and Tolerability of ZYN002 Administered as a Transdermal Gel to Children and Adolescents With Fragile X Syndrome - CONNECT-FX Open Label Extension (OLE) Recruiting NCT03802799 Phase 2, Phase 3 ZYN002 - CBD Transdermal Gel
10 Double-Blind, Placebo-Controlled Proof of Concept Study in Youth With Fragile X Syndrome Active, not recruiting NCT01911455 Phase 2, Phase 3 acamprosate;Placebo
11 An Open-label Study to Evaluate the Long-term Safety and Tolerability of AFQ056 in Adolescent Patients With Fragile X Syndrome Terminated NCT01433354 Phase 2, Phase 3 AFQ056
12 An Open-Label Extension Study to Evaluate the Safety, Tolerability, and Pharmacokinetics in Subject With Fragile X Syndrome Terminated NCT01555333 Phase 3 arbaclofen
13 A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate the Efficacy and Safety of AFQ056 in Adolescent Patients With Fragile X Syndrome Completed NCT01357239 Phase 2 AFQ056;Placebo
14 A Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Evaluate AFQ056 in Adult Patients With Fragile X Syndrome Completed NCT01253629 Phase 2 AFQ056;Placebo
15 A Multi-centre, Randomized, Double-blind, Placebo Controlled, Two-period, Crossover Proof-of-concept Study in Male Patients With Fragile X Syndrome to Assess the Efficacy, Safety and Tolerability of Multiple Oral Doses of AFQ056 Completed NCT00718341 Phase 2 AF056;Placebo
16 A Double-Blind, Placebo-Controlled, Crossover, Flexible-Dose Evaluation of the Efficacy, Safety and Tolerability of STX209 in the Treatment of Irritability in Subjects With Fragile X Syndrome Completed NCT00788073 Phase 2 STX209;Placebo
17 An Open Label Exploratory Study to Investigate the Safety and Effects of NPL-2009 ( 50 mg - 150 mg Single Dose) on Prepulse Inhibition Tests and Continuous Performance Tasks, in Adults With Fragile X Syndrome Completed NCT00637221 Phase 1, Phase 2 NPL-2009
18 A Randomized, Parallel Group, Double-Blind, Placebo-Controlled, Safety and Exploratory Efficacy and Pharmacokinetic, Study of RO4917523 in Pediatric Patients With Fragile X Syndrome Completed NCT01750957 Phase 2 Placebo;RO4917523;RO4917523
19 Aripiprazole in Fragile X Syndrome Completed NCT00420459 Phase 2 Aripiprazole
20 Pilot Study of Acamprosate in Youth With Fragile X Syndrome Completed NCT01300923 Phase 2 Acamprosate
21 A Randomized, Double-blind, 12-week, Parallel Group, Placebo-controlled Study of Efficacy and Safety of RO4917523 in Patients With Fragile X Syndrome. Completed NCT01517698 Phase 2 Placebo;RO4917523 0.5 mg;RO4917523 1.5 mg
22 A Randomized, Double-blind, Placebo-controlled, Pharmacokinetic, Safety and Tolerability, and Exploratory Efficacy and Pharmacodynamic Effects Study of RO4917523 in Adult Patients With Fragile X Syndrome. Completed NCT01015430 Phase 2 Placebo (for RO4917523 ascending doses);Placebo (for RO4917523 fixed dose);RO4917523;RO4917523
23 A Phase II Randomized, Double-Blind, Placebo-Controlled, Parallel-Group, Fixed-Dose Study of NNZ-2566 in Fragile X Syndrome Completed NCT01894958 Phase 2 NNZ-2566;Placebo
24 A 6-week, Randomized, Multicenter, Double-blind, Parallel, Flexed and Fixed-dose Study of MG01CI (Metadoxine Extended-release) Low Dose and High Dose Compared With Placebo in Adults and Adolescents With Fragile X Syndrome Completed NCT02126995 Phase 2 MG01CI extended-release tablet
25 A Controlled, Double-blind, Crossover Trial of Ganaxolone in Children With Fragile X Syndrome Completed NCT01725152 Phase 2 Ganaxolone;Placebo
26 A Pilot Study Exploring the Safety and Synergistic Effect of a Minocycline/Lovastatin Combined Treatment on the Behavior of Individuals With Fragile X Syndrome; Validation of New Biochemical and Neurophysiological Markers (LovaMiX) Completed NCT02680379 Phase 2 Minocycline, then Minocycline/Lovastatin;Lovastatin, then Minocycline/Lovastatin
27 Double-blind Placebo Controlled Study of Oxytocin in Fragile X Syndrome Completed NCT01254045 Phase 2 placebo;oxytocin 24IU;oxytocin 48IU
28 Phase II Double-blind Randomized Placebo-controlled 1-way Crossover Trial to Investigate Safety and Efficacy of the Ascorbic Acid and Tocopherol for the Treatment of the Fragile X Syndrome Completed NCT01329770 Phase 2
29 A Controlled Trial of Sertraline in Young Children With Fragile X Syndrome Completed NCT01474746 Phase 2 Sertraline;Placebo
30 Effects of Ampakine CX516 (Ampalex®) on Functioning in Fragile X Syndrome and Autism Completed NCT00054730 Phase 2 CX516 (Ampalex®)
31 Estrogen Receptors Beta (ER-B) as Therapeutic Targets for the Improvement of Cognitive Performance in Fragile-X (TESXF) Completed NCT01855971 Phase 2
32 Augmentation of the Cholinergic System in Fragile X Syndrome: A Double-Blind Placebo-Controlled Randomized Study of Donepezil Completed NCT01120626 Phase 2 donepezil;sugar pill
33 The ScanBrit Randomised Controlled Study of Gluten- and Casein-free Dietary Intervention for Children With Autism Spectrum Disorders Completed NCT00614198 Phase 2
34 Folate Rechallenge: A Pilot Study Completed NCT00672360 Phase 2
35 A Randomized, Double-blind, Placebo-controlled, 2-period Crossover Study of BPN14770 in Adult Males With Fragile X Syndrome Recruiting NCT03569631 Phase 2 BPN14770;Placebo
36 Effects of Social Gaze Training on Brain and Behavior in Fragile X Syndrome Recruiting NCT02616796 Phase 1, Phase 2
37 Evaluate the Efficacy and Safety of Metformin in Children and Adults With Fragile X Syndrome: an Open-label Study Recruiting NCT03722290 Phase 2 Metformin
38 A Parallel Group Design Randomized Double-Blind Trial of Metformin Treatment in Patients With Fragile X Syndrome on Safety and Effects on Cognition, Anxiety, Attention and Biomarkers Recruiting NCT04141163 Phase 1, Phase 2 Metformin;Placebo oral tablet
39 Effects of AFQ056 on Language Learning in Young Children With Fragile X Syndrome (FXS) Recruiting NCT02920892 Phase 2 AFQ056
40 A Double-Blind, Placebo-Controlled Trial of Metformin in Individuals With Fragile X Syndrome (FXS) Recruiting NCT03862950 Phase 2 Placebo Medication;Metformin
41 A Phase 2, Randomized, Double-Blind, Parallel-Group Study Evaluating the Safety, Tolerability, and Efficacy of OV101 in Fragile X Syndrome Active, not recruiting NCT03697161 Phase 2 OV101 (gaboxadol)
42 Evaluating the Neurophysiologic and Clinical Effects of Single-Dose Acamprosate, Lovastatin, Minocycline and Placebo in Fragile X Syndrome Enrolling by invitation NCT02998151 Phase 2 Acamprosate;Lovastatin;Minocycline;Placebo
43 A Randomized, Double-Blind, Placebo-Controlled Study to Assess the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of a Single Dose of STX107 in Adults With Fragile X Syndrome Suspended NCT01325740 Phase 2 STX107
44 An Open-label Study to Evaluate the Long-term Safety, Tolerability and Efficacy of AFQ056 in Adult Patients With Fragile X Syndrome Terminated NCT01348087 Phase 2 AFQ056
45 An Open Label Extension Study to Evaluate the Safety, Tolerability and Pharmacokinetics of STX209 in Subjects With Fragile X Syndrome Terminated NCT01013480 Phase 2 Arbaclofen
46 PREDICTORS (Parents Resources for Decreasing the Incidence of Change Triggered Temper Outbursts) Unknown status NCT02567357 Phase 1
47 Sequential, Two-period Study to Assess the Pharmacokinetics, Safety & Tolerability of Single and Multiple Oral Doses of AFQ056 in Patients With FXS (Fragile X Syndrome) Aged 5-11 Years (Cohort 1) and 3-4 Years (Cohort 2) Completed NCT01482143 Phase 1 AFQ056
48 A Phase 1 Single Dose PK Study in Adolescent Subjects With Fragile X Syndrome or Angelman Syndrome Completed NCT03109756 Phase 1 OV101
49 An Open-Label Trial of Donepezil in Fragile X Syndrome Completed NCT00220584 Phase 1 donepezil
50 Glutaminergic Transmission in Autism : Molecular Imaging Exploration Completed NCT02719951 Phase 1 [18F]FPEB PET imaging

Search NIH Clinical Center for Fragile X Syndrome

Cochrane evidence based reviews: fragile x syndrome

Genetic Tests for Fragile X Syndrome

Genetic tests related to Fragile X Syndrome:

# Genetic test Affiliating Genes
1 Fragile X Syndrome 29 FMR1
2 Fraxe 29 AFF2
3 Mental Retardation, X-Linked, Fraxe Type 29

Anatomical Context for Fragile X Syndrome

MalaCards organs/tissues related to Fragile X Syndrome:

40
Brain, Testes, Cortex, Eye, Amygdala, Prefrontal Cortex, Cerebellum

Publications for Fragile X Syndrome

Articles related to Fragile X Syndrome:

(show top 50) (show all 4703)
# Title Authors PMID Year
1
A point mutation in the FMR-1 gene associated with fragile X mental retardation. 54 61 6 56
8490650 1993
2
A nonsense mutation in FMR1 causing fragile X syndrome. 6 56 61
21267007 2011
3
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 56 61
1605193 1992
4
Mapping of DNA instability at the fragile X to a trinucleotide repeat sequence p(CCG)n. 6 61 56
1675488 1991
5
Intention tremor, parkinsonism, and generalized brain atrophy in male carriers of fragile X. 56 6
11445641 2001
6
Incidence of fragile X syndrome by newborn screening for methylated FMR1 DNA. 61 54 56
19804849 2009
7
Neuroanatomy of fragile X syndrome is associated with aberrant behavior and the fragile X mental retardation protein (FMRP). 54 61 56
17932962 2008
8
Deletion of FMR1 in Purkinje cells enhances parallel fiber LTD, enlarges spines, and attenuates cerebellar eyelid conditioning in Fragile X syndrome. 61 56 54
16055059 2005
9
Noninvasive test for fragile X syndrome, using hair root analysis. 56 61 54
10364521 1999
10
FMRP associates with polyribosomes as an mRNP, and the I304N mutation of severe fragile X syndrome abolishes this association. 54 6 61
9659908 1997
11
Fragile X syndrome is less common than previously estimated. 54 61 56
9032640 1997
12
A female compound heterozygote (pre- and full mutation) for the CGG FMR1 expansion. 61 54 56
8792815 1996
13
Intragenic loss of function mutations demonstrate the primary role of FMR1 in fragile X syndrome. 6 54 61
7670500 1995
14
Variation of the CGG repeat at the fragile X site results in genetic instability: resolution of the Sherman paradox. 61 56 54
1760838 1991
15
Absence of expression of the FMR-1 gene in fragile X syndrome. 54 61 56
1878973 1991
16
EMQN best practice guidelines for the molecular genetic testing and reporting of fragile X syndrome and other fragile X-associated disorders. 6 61
25227148 2015
17
Cholesterol levels in fragile X syndrome. 56 61
25424470 2015
18
Frequency of FMR1 gene mutation and CGG repeat polymorphism in intellectually disabled children in Pakistan. 56 61
24478267 2014
19
Promoter-bound trinucleotide repeat mRNA drives epigenetic silencing in fragile X syndrome. 61 56
24578575 2014
20
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. 6 61
23765048 2013
21
Genetic counseling and testing for FMR1 gene mutations: practice guidelines of the national society of genetic counselors. 6 61
22797890 2012
22
Increased prevalence of seizures in boys who were probands with the FMR1 premutation and co-morbid autism spectrum disorder. 61 56
22001913 2012
23
Fragile X syndrome: from molecular genetics to therapy. 56 61
19724010 2009
24
No evidence for a difference in neuropsychological profile among carriers and noncarriers of the FMR1 premutation in adults under the age of 50. 56 61
19026394 2008
25
Tdrd3 is a novel stress granule-associated protein interacting with the Fragile-X syndrome protein FMRP. 61 6
18664458 2008
26
Fragile X syndrome with anxiety disorder and exceptional verbal intelligence. 56 61
18203169 2008
27
A unique case of reversion to normal size of a maternal premutation FMR1 allele in a normal boy. 56 61
17971832 2008
28
Fragile-X syndrome and fragile X-associated tremor/ataxia syndrome: two faces of FMR1. 56 61
17166801 2007
29
Periventricular heterotopia in fragile X syndrome. 56 61
16924033 2006
30
A cryptic full mutation in a male with a classical fragile X phenotype. 56 61
16813602 2006
31
No evidence of paternal transmission of fragile X syndrome. 61 56
15887276 2005
32
Kissing complex RNAs mediate interaction between the Fragile-X mental retardation protein KH2 domain and brain polyribosomes. 6 61
15805463 2005
33
Five years of molecular diagnosis of Fragile X syndrome (1997-2001): a collaborative study reporting 95% of the activity in France. 61 56
15326620 2004
34
Paternal transmission of fragile X syndrome. 61 56
15316964 2004
35
Clinical features of boys with fragile X premutations and intermediate alleles. 56 61
12898586 2003
36
Predictive testing for cognitive functioning in female carriers of the fragile X syndrome using hair root analysis. 61 56
12746404 2003
37
Prevalence of the fragile X syndrome in African-Americans. 56 61
12116230 2002
38
Premutation and intermediate-size FMR1 alleles in 10572 males from the general population: loss of an AGG interruption is a late event in the generation of fragile X syndrome alleles. 61 56
11854169 2002
39
Analysis of FMR1 (CGG)(n) alleles and DXS548-FRAXAC1 haplotypes in three European circumpolar populations: traces of genetic relationship with Asia. 61 56
11571563 2001
40
Fragile-X carrier screening and the prevalence of premutation and full-mutation carriers in Israel. 61 56
11443541 2001
41
Problems in the diagnosis of fragile X syndrome in young children are still present. 61 56
11298371 2001
42
Unilateral macroorchidism in fragile X syndrome. 56 61
11146477 2000
43
Melatonin profiles and sleep characteristics in boys with fragile X syndrome: a preliminary study. 61 56
11186882 2000
44
Cognitive and behavioral profile of fragile X boys: correlations to molecular data. 61 56
11078566 2000
45
Physical characteristics of young boys with fragile X syndrome: reasons for difficulties in making a diagnosis in young males. 56 61
10842286 2000
46
Absence of fragile X syndrome in Nova Scotia. 56 61
10691418 2000
47
Analysis of FMR1 (CGG)n alleles and FRAXA microsatellite haplotypes in the population of Greenland: implications for the population of the New World from Asia. 56 61
10573009 1999
48
Compound heterozygous female with fragile X syndrome. 61 56
10208169 1999
49
FMR1 gene expression in olfactory neuroblasts from two males with fragile X syndrome. 61 56
9916838 1999
50
FMR1 Disorders 6 61
20301558 1998

Variations for Fragile X Syndrome

ClinVar genetic disease variations for Fragile X Syndrome:

6 (show all 15) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 FMR1 NM_002024.5(FMR1):c.52-1_52delinsTAindel Pathogenic 9971 rs1557176576 X:147003450-147003451 X:147921932-147921933
2 FMR1 FMR1, (CGG)n EXPANSIONNT expansion Pathogenic 9972
3 FMR1 NM_002024.5(FMR1):c.911T>A (p.Ile304Asn)SNV Pathogenic 9969 rs121434622 X:147018053-147018053 X:147936534-147936534
4 FMR1 NM_002024.5(FMR1):c.373del (p.Thr125fs)deletion Pathogenic 9970 rs1569545562 X:147010279-147010279 X:147928761-147928761
5 AFF2 NM_001169122.1(AFF2):c.-460_-458GCC(6_25)NT expansion Pathogenic 10526 rs193922937 X:147582158-147582160 X:148500638-148500640
6 SERPINA1 NM_001127701.1(SERPINA1):c.1096G>A (p.Glu366Lys)SNV Pathogenic 17967 rs28929474 14:94844947-94844947 14:94378610-94378610
7 FMR1 NM_002024.5(FMR1):c.80C>A (p.Ser27Ter)SNV Pathogenic 29987 rs1569545382 X:147003479-147003479 X:147921961-147921961
8 AFF2 AFF2, 121- to 145-KB DELdeletion Pathogenic 29983
9 FMR1 NM_002024.5(FMR1):c.-128_-126(200)NT expansion Pathogenic 183387 rs193922936 X:146993570-146993572 X:147912052-147912054
10 FMR1 NC_000023.9:g.146703942_146820448deldeletion Pathogenic 183388
11 ADGB , GRM1 , LOC101928661 , LOC114004398 , RAB32 NC_000006.11:g.146735206_147036914del301709deletion Pathogenic 242923 6:146735206-147036914 6:146414070-146715778
12 FMR1 NM_002024.5(FMR1):c.-128GGC[>200]undetermined variant Pathogenic 623468
13 AFF2 GRCh37/hg19 Xq28(chrX:147642893-147870805)copy number loss Pathogenic 625801 X:147642893-147870805
14 AFF2 NM_002025.4(AFF2):c.*4554C>GSNV Uncertain significance 219173 rs864321652 X:148077416-148077416 X:148995886-148995886
15 AFF2 NM_002025.4(AFF2):c.1830G>C (p.Leu610Phe)SNV Uncertain significance 128283 rs200450195 X:148037405-148037405 X:148955875-148955875

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

73
# Symbol AA change Variation ID SNP ID
1 FMR1 p.Ile304Asn VAR_005234 rs121434622
2 FMR1 p.Arg138Gln VAR_064507 rs200163413
3 FMR1 p.Gly266Glu VAR_075977

Copy number variations for Fragile X Syndrome from CNVD:

7
# CNVD ID Chromosome Start End Type Gene Symbol CNVD Disease
1 60593 11 88300000 92800000 Copy number GRM5 Fragile x
2 259561 X 137800000 146900000 Copy number FMR1 Fragile x

Expression for Fragile X Syndrome

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

Pathways for Fragile X Syndrome

Pathways related to Fragile X Syndrome according to KEGG:

36
# Name Kegg Source Accession
1 RNA transport hsa03013

Pathways related to Fragile X Syndrome according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.7 MECP2 GRM5 GRM1 GRIA1 FXR2 FXR1
2
Show member pathways
11.66 GRM5 GRM1 GRIA1
3 11.47 FXR2 FXR1 FMR1 CYFIP1
4 11.12 MECP2 GRIA1 BDNF
5 10.53 GRM5 GRM1
6 10.4 GRM1 BDNF

GO Terms for Fragile X Syndrome

Cellular components related to Fragile X Syndrome according to GeneCards Suite gene sharing:

(show all 18)
# Name GO ID Score Top Affiliating Genes
1 axon GO:0030424 9.93 MAP1B FXR2 FXR1 FMR1 BDNF
2 dendrite GO:0030425 9.93 MAP1B GRM1 GRIA1 FXR1 FMR1 BDNF
3 neuron projection GO:0043005 9.91 SLC6A4 GRM5 GRM1 GRIA1 FMR1 CYFIP1
4 neuronal cell body GO:0043025 9.88 MAP1B GRIA1 FXR2 FXR1 FMR1 CYFIP1
5 presynapse GO:0098793 9.81 SLC6A4 FXR2 FXR1 FMR1
6 growth cone GO:0030426 9.8 MAP1B FXR2 FXR1 FMR1
7 postsynaptic density GO:0014069 9.8 MAP1B GRM1 GRIA1 FXR2 FXR1 FMR1
8 cytoplasmic ribonucleoprotein granule GO:0036464 9.72 FXR2 FXR1 FMR1
9 polysome GO:0005844 9.7 FXR2 FXR1 FMR1
10 postsynaptic density membrane GO:0098839 9.65 GRM5 GRM1 GRIA1
11 postsynapse GO:0098794 9.65 MECP2 GRIA1 FXR1 FMR1 CYFIP1
12 filopodium tip GO:0032433 9.58 FMR1 CYFIP1
13 somatodendritic compartment GO:0036477 9.57 MAP1B GRIA1
14 mRNA cap binding complex GO:0005845 9.56 FMR1 CYFIP1
15 ribonucleoprotein granule GO:0035770 9.54 FXR2 FXR1 FMR1
16 dendritic spine neck GO:0044326 9.33 FXR2 FXR1 FMR1
17 dendritic filopodium GO:1902737 9.13 FXR2 FXR1 FMR1
18 dendritic spine GO:0043197 9.1 MAP1B GRIA1 FXR2 FXR1 FMR1 CYFIP1

Biological processes related to Fragile X Syndrome according to GeneCards Suite gene sharing:

(show all 14)
# Name GO ID Score Top Affiliating Genes
1 chemical synaptic transmission GO:0007268 9.8 MECP2 GRM5 GRM1 GRIA1
2 regulation of mRNA stability GO:0043488 9.71 FXR2 FXR1 FMR1
3 memory GO:0007613 9.69 SLC6A4 MECP2 BDNF
4 negative regulation of translation GO:0017148 9.63 FXR2 FXR1 FMR1
5 positive regulation of translation GO:0045727 9.61 FXR2 FXR1 FMR1
6 regulation of alternative mRNA splicing, via spliceosome GO:0000381 9.58 FXR2 FXR1 FMR1
7 synapse assembly GO:0007416 9.54 MECP2 MAP1B BDNF
8 G protein-coupled glutamate receptor signaling pathway GO:0007216 9.52 GRM5 GRM1
9 regulation of postsynaptic membrane potential GO:0060078 9.5 GRM5 GRM1 GRIA1
10 positive regulation of gene silencing by miRNA GO:2000637 9.48 FXR1 FMR1
11 positive regulation of response to DNA damage stimulus GO:2001022 9.43 FXR2 FXR1 FMR1
12 regulation of filopodium assembly GO:0051489 9.33 FXR2 FXR1 FMR1
13 regulation of postsynaptic cytosolic calcium ion concentration GO:0099566 9.13 GRM5 GRM1 GRIA1
14 regulation of translation GO:0006417 9.02 GRM5 FXR2 FXR1 FMR1 CYFIP1

Molecular functions related to Fragile X Syndrome according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mRNA binding GO:0003729 9.67 MECP2 FXR2 FXR1 FMR1
2 mRNA 3'-UTR binding GO:0003730 9.61 FXR2 FXR1 FMR1
3 siRNA binding GO:0035197 9.46 MECP2 FMR1
4 G-quadruplex RNA binding GO:0002151 9.4 FMR1 AFF2
5 glutamate receptor activity GO:0008066 9.33 GRM5 GRM1 GRIA1
6 RNA strand annealing activity GO:0033592 9.32 FXR1 FMR1
7 G protein-coupled receptor activity involved in regulation of postsynaptic membrane potential GO:0099530 9.26 GRM5 GRM1
8 translation regulator activity GO:0045182 9.26 FXR2 FXR1 FMR1 CYFIP1
9 neurotransmitter receptor activity involved in regulation of postsynaptic cytosolic calcium ion concentration GO:0099583 8.8 GRM5 GRM1 GRIA1

Sources for Fragile X Syndrome

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
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