Fragile X syndrome

General Information (adopted from Orphanet):

Synonyms, Signs: FRAGILE X PREMATURE OVARIAN FAILURE, INCLUDED
MARKER X SYNDROME
MARTIN-BELL SYNDROME PRIMARY OVARIAN INSUFFICIENCY, FRAGILE X-ASSOCIATED, INCLUDED
X-LINKED MENTAL RETARDATION AND MACROORCHIDISM
FRAGILE X SYNDROME
FXS
MENTAL RETARDATION, X-LINKED, ASSOCIATED WITH marXq28
FraX syndrome
Martin-Bell syndrome
FRAXA syndrome
Number of Symptoms 45
OrphanetNr: 908
OMIM Id: 300624
ICD-10: Q99.2
UMLs: C0016667
C0751156
MeSH: D005600
MedDRA: 10017324
Snomed: 254287005
613003

Prevalence, inheritance and age of onset:

Prevalence: 20 of 100 000 [Orphanet]
Inheritance: X-linked dominant
[Orphanet]
Age of onset: Neonatal
Infancy
Childhood
[Orphanet]

Disease classification (adopted from Orphanet):

Parent Diseases: Chromosomal anomaly with epilepsy as a major feature
 -Rare neurologic disease
Motor stereotypies
 -Rare genetic disease
 -Rare neurologic disease
Multiple congenital anomalies/dysmorphic syndrome-intellectual deficit
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
Rare disease with autism
 -Rare genetic disease
 -Rare neurologic disease
Syndrome associated with Pierre Robin syndrome
 -Rare developmental defect during embryogenesis
 -Rare genetic disease
 -Rare maxillo-facial surgical disease
 -Rare otorhinolaryngologic disease
Syndrome with a symptomatic strabismus
 -Rare eye disease
 -Rare genetic disease
Syndromic obesity
 -Rare developmental defect during embryogenesis
 -Rare endocrine disease
 -Rare genetic disease
X-linked syndromic intellectual deficit
 -Rare genetic disease
 -Rare neurologic disease

Symptom Information: Sort by abundance 

1
(HPO:0008640) Congenital macroorchidism 1 / 7739
2
(HPO:0002050) Macroorchidism, postpubertal 2 / 7739
3
(HPO:0000053) Macroorchidism Very frequent [Orphanet] 18 / 7739
4
(HPO:0002003) Large forehead 9 / 7739
5
(HPO:0000303) Mandibular prognathia Frequent [Orphanet] 179 / 7739
6
(HPO:0000276) Long face Frequent [Orphanet] 109 / 7739
7
(HPO:0000256) Macrocephaly Frequent [Orphanet] 298 / 7739
8
(HPO:0000280) Coarse facial features 189 / 7739
9
(HPO:0000275) Narrow face Frequent [Orphanet] 76 / 7739
10
(HPO:0002007) Frontal bossing Frequent [Orphanet] 366 / 7739
11
(HPO:0000246) Sinusitis Frequent [Orphanet] 73 / 7739
12
(HPO:0000486) Strabismus Occasional [Orphanet] 576 / 7739
13
(HPO:0000400) Macrotia 108 / 7739
14
(HPO:0000389) Chronic otitis media Very frequent [Orphanet] 64 / 7739
15
(HPO:0000411) Protruding ear Frequent [Orphanet] 140 / 7739
16
(HPO:0002457) Abnormal head movements 1 / 7739
17
(HPO:0000817) Poor eye contact 26 / 7739
18
(HPO:0000717) Autism Occasional [Orphanet] 108 / 7739
19
(HPO:0002342) Intellectual disability, moderate typical [HPO:skoehler] 37 / 7739
20
(HPO:0100851) Abnormal emotion/affect behavior Occasional [Orphanet] 85 / 7739
21
(HPO:0000752) Hyperactivity Frequent [Orphanet] 140 / 7739
22
(HPO:0002167) Neurological speech impairment Very frequent [Orphanet] 308 / 7739
23
(HPO:0000708) Behavioral abnormality Occasional [Orphanet] 212 / 7739
24
(HPO:0001250) Seizures Occasional [Orphanet] 1245 / 7739
25
(HPO:0001249) Intellectual disability 1089 / 7739
26
(HPO:0100716) Self-injurious behavior Occasional [Orphanet] 43 / 7739
27
(HPO:0001388) Joint laxity 117 / 7739
28
(HPO:0000767) Pectus excavatum 244 / 7739
29
(HPO:0001763) Pes planus Very frequent [Orphanet] 176 / 7739
30
(HPO:0002650) Scoliosis 705 / 7739
31
(HPO:0001382) Joint hypermobility Very frequent [Orphanet] 231 / 7739
32
(HPO:0002577) Abnormality of the stomach Frequent [Orphanet] 84 / 7739
33
(HPO:0001634) Mitral valve prolapse 69 / 7739
34
(HPO:0001633) Abnormality of the mitral valve Occasional [Orphanet] 69 / 7739
35
(HPO:0002616) Aortic root dilatation Occasional [Orphanet] 27 / 7739
36
(HPO:0003220) Abnormality of chromosome stability Very frequent [Orphanet] 98 / 7739
37
(HPO:0003564) Folate-dependent fragile site at Xq28 1 / 7739
38
(HPO:0001252) Muscular hypotonia Frequent [Orphanet] 990 / 7739
39
(HPO:0003829) Incomplete penetrance 85 / 7739
40
(OMIM) Periventricular heterotopia 1 / 7739
41
(HPO:0012758) Neurodevelopmental delay Very frequent [Orphanet] 949 / 7739
42
(OMIM) [DEL]Autistic features 43 / 7739
43
(HPO:0002120) Cerebral cortical atrophy Occasional [Orphanet] 187 / 7739
44
(HPO:0001423) X-linked dominant inheritance 69 / 7739
45
(HPO:0007165) Periventricular gray matter heterotopia 4 / 7739

Associated genes:

ClinVar (via SNiPA)

Gene symbol Variation Clinical significance Reference

Additional Information:

Description: (OMIM) Fragile X mental retardation 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 ...
Diagnosis OMIM Jacky and Dill (1980) detected the fragile X chromosome in cultured lymphocytes and fibroblasts from affected patients. Glover (1981), Tommerup et al. (1981), and Jacobs et al. (1982) demonstrated that pharmacologic inhibition of thymidylate synthetase (TYMS; 188350) was ...
Clinical Description OMIM Lubs (1969) reported a family in which 4 males spanning 3 generations had mental retardation. Cytogenetic studies showed an unusual constriction of the long arm of the X chromosome in 10 to 33% of cells. In a follow-up ...
Molecular genetics OMIM - Nomenclature of Expanded Trinucleotide Repeats

The repeat involved in the fragile X syndrome is variously referred to here as (CGG)n or (CCG)n. The identical repeat found in the cloned FRAXE gene (309548) was referred to ...

Population genetics OMIM Jacobs (1982) indicated that a reasonable estimate of frequency of fragile X syndrome is 0.5 per 1,000 males. Although many of the cases first ascertained were of northern European descent, affected males have since been found in most ...