MRXS99F
MCID: MNT290
MIFTS: 30

Mental Retardation, X-Linked 99, Syndromic, Female-Restricted (MRXS99F)

Categories: Fetal diseases, Genetic diseases, Mental diseases, Neuronal diseases, Rare diseases

Aliases & Classifications for Mental Retardation, X-Linked 99, Syndromic, Female-Restricted

MalaCards integrated aliases for Mental Retardation, X-Linked 99, Syndromic, Female-Restricted:

Name: Mental Retardation, X-Linked 99, Syndromic, Female-Restricted 57 72 29 6
X-Linked Female Restricted Facial Dysmorphism-Short Stature-Choanal Atresia-Intellectual Disability 12 20 58
Mrxs99f 57 12 72
X-Linked Facial Dysmorphism-Short Stature-Choanal Atresia-Intellectual Disability Syndrome Limited to Females 20 58
Female-Restricted Syndromic X-Linked Intellectual Disability 99 12
Female-Restricted X-Linked Syndromic Intellectual Disability-99 20
Female-Restricted Syndromic X-Linked Mental Retardation 99 12

Characteristics:

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
highly variable phenotype
mutations occur de novo

Inheritance:
x-linked dominant


HPO:

31
mental retardation, x-linked 99, syndromic, female-restricted:
Inheritance x-linked dominant inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


Summaries for Mental Retardation, X-Linked 99, Syndromic, Female-Restricted

UniProtKB/Swiss-Prot : 72 Mental retardation, X-linked 99, syndromic, female-restricted: A form of mental retardation, a disorder characterized by significantly below average general intellectual functioning, associated with impairments in adaptive behavior and manifested during the developmental period. MRXS99F affected females manifest intellectual disability, developmental delay, facial dysmorphism, short stature, and distinct congenital malformations comprising choanal atresia, anal abnormalities, post-axial polydactyly, heart defects, hypomastia, cleft palate/bifid uvula, progressive scoliosis, and structural brain abnormalities. Inheritance is X-linked dominant.

MalaCards based summary : Mental Retardation, X-Linked 99, Syndromic, Female-Restricted, is also known as x-linked female restricted facial dysmorphism-short stature-choanal atresia-intellectual disability. An important gene associated with Mental Retardation, X-Linked 99, Syndromic, Female-Restricted is USP9X (Ubiquitin Specific Peptidase 9 X-Linked). Affiliated tissues include thyroid, brain and eye, and related phenotypes are global developmental delay and intellectual disability, moderate

Disease Ontology : 12 A syndromic X-linked intellectual disability characterized by delayed psychomotor development, mild to moderate intellectual disability, and a wide range of additional congenital anomalies that has material basis in heterozygous mutation in USP9X on chromosome Xp11.4.

OMIM® : 57 Female-restricted X-linked syndromic mental retardation-99 is an X-linked dominant neurodevelopmental disorder characterized by delayed psychomotor development and mild to moderate intellectual disability. Affected females can have a wide range of additional congenital anomalies, including scoliosis, postaxial polydactyly, mild cardiac or urogenital anomalies, dysmorphic facial features, and mild structural brain abnormalities (summary by Reijnders et al., 2016). (300968) (Updated 05-Apr-2021)

Related Diseases for Mental Retardation, X-Linked 99, Syndromic, Female-Restricted

Symptoms & Phenotypes for Mental Retardation, X-Linked 99, Syndromic, Female-Restricted

Human phenotypes related to Mental Retardation, X-Linked 99, Syndromic, Female-Restricted:

58 31 (show top 50) (show all 104)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 global developmental delay 58 31 very rare (1%) Very frequent (99-80%) HP:0001263
2 intellectual disability, moderate 58 31 hallmark (90%) Very frequent (99-80%) HP:0002342
3 short stature 58 31 frequent (33%) Frequent (79-30%) HP:0004322
4 anal atresia 58 31 very rare (1%) Frequent (79-30%) HP:0002023
5 choanal atresia 58 31 very rare (1%) Frequent (79-30%) HP:0000453
6 dandy-walker malformation 58 31 very rare (1%) Frequent (79-30%) HP:0001305
7 hypoplasia of the corpus callosum 58 31 very rare (1%) Frequent (79-30%) HP:0002079
8 abnormal cortical gyration 58 31 very rare (1%) Frequent (79-30%) HP:0002536
9 infantile muscular hypotonia 58 31 frequent (33%) Frequent (79-30%) HP:0008947
10 depigmentation/hyperpigmentation of skin 58 31 frequent (33%) Frequent (79-30%) HP:0007483
11 postaxial polydactyly 58 31 very rare (1%) Frequent (79-30%) HP:0100259
12 high palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000218
13 osteopenia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000938
14 hearing impairment 58 31 very rare (1%) Occasional (29-5%) HP:0000365
15 cataract 58 31 occasional (7.5%) Occasional (29-5%) HP:0000518
16 depressed nasal bridge 58 31 occasional (7.5%) Occasional (29-5%) HP:0005280
17 gingival overgrowth 58 31 occasional (7.5%) Occasional (29-5%) HP:0000212
18 hip dysplasia 58 31 very rare (1%) Occasional (29-5%) HP:0001385
19 wide nasal bridge 58 31 occasional (7.5%) Occasional (29-5%) HP:0000431
20 pes planus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001763
21 thick vermilion border 58 31 occasional (7.5%) Occasional (29-5%) HP:0012471
22 delayed puberty 58 31 occasional (7.5%) Occasional (29-5%) HP:0000823
23 brachycephaly 58 31 occasional (7.5%) Occasional (29-5%) HP:0000248
24 prominent forehead 58 31 occasional (7.5%) Occasional (29-5%) HP:0011220
25 strabismus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000486
26 cleft palate 58 31 occasional (7.5%) Occasional (29-5%) HP:0000175
27 myopia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000545
28 atrial septal defect 58 31 occasional (7.5%) Occasional (29-5%) HP:0001631
29 congenital hip dislocation 58 31 occasional (7.5%) Occasional (29-5%) HP:0001374
30 joint laxity 58 31 occasional (7.5%) Occasional (29-5%) HP:0001388
31 downslanted palpebral fissures 58 31 occasional (7.5%) Occasional (29-5%) HP:0000494
32 neoplasm 58 31 occasional (7.5%) Occasional (29-5%) HP:0002664
33 upslanted palpebral fissure 58 31 occasional (7.5%) Occasional (29-5%) HP:0000582
34 facial asymmetry 58 31 occasional (7.5%) Occasional (29-5%) HP:0000324
35 low-set, posteriorly rotated ears 58 31 occasional (7.5%) Occasional (29-5%) HP:0000368
36 patent ductus arteriosus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001643
37 hydronephrosis 58 31 occasional (7.5%) Occasional (29-5%) HP:0000126
38 thin upper lip vermilion 58 31 occasional (7.5%) Occasional (29-5%) HP:0000219
39 long philtrum 58 31 occasional (7.5%) Occasional (29-5%) HP:0000343
40 telecanthus 58 31 occasional (7.5%) Occasional (29-5%) HP:0000506
41 sacral dimple 58 31 very rare (1%) Occasional (29-5%) HP:0000960
42 hallux valgus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001822
43 pes cavus 58 31 occasional (7.5%) Occasional (29-5%) HP:0001761
44 small hand 58 31 occasional (7.5%) Occasional (29-5%) HP:0200055
45 limitation of joint mobility 58 31 occasional (7.5%) Occasional (29-5%) HP:0001376
46 cerebellar hypoplasia 58 31 very rare (1%) Occasional (29-5%) HP:0001321
47 tapered finger 58 31 occasional (7.5%) Occasional (29-5%) HP:0001182
48 short foot 58 31 occasional (7.5%) Occasional (29-5%) HP:0001773
49 hypoplastic nipples 58 31 occasional (7.5%) Occasional (29-5%) HP:0002557
50 misalignment of teeth 58 31 occasional (7.5%) Occasional (29-5%) HP:0000692

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Skeletal Spine:
scoliosis

Respiratory:
recurrent respiratory infections
breathing difficulties, neonatal

Growth Height:
short stature

Head And Neck Eyes:
strabismus
myopia
astigmatism
hypermetropia
cataracts
more
Cardiovascular Heart:
atrial septal defect
congenital heart malformations, mild

Abdomen Gastrointestinal:
anal atresia
feeding difficulties

Cardiovascular Vascular:
patent ductus arteriosus

Neurologic Central Nervous System:
dandy-walker malformation
cerebellar hypoplasia
hypoplasia of the corpus callosum
enlarged ventricles
seizures (in some patients)
more
Skeletal Feet:
pes cavus
small feet

Skeletal Hands:
postaxial polydactyly
small hands
tapering fingers

Head And Neck Teeth:
tooth abnormalities

Endocrine Features:
thyroid abnormalities

Skeletal Pelvis:
hip dysplasia
hip dislocation

Head And Neck Face:
smooth philtrum
prominent forehead
facial asymmetry
long philtrum
bitemporal narrowing
more
Head And Neck Head:
brachycephaly

Head And Neck Ears:
low-set ears
posteriorly rotated ears
hearing loss

Skeletal:
joint laxity

Head And Neck Nose:
choanal atresia
bulbous nose
prominent nose
broad nasal bridge
low nasal bridge
more
Genitourinary Kidneys:
hydronephrosis
renal dysplasia

Skin Nails Hair Skin:
sacral dimple
pigmentary abnormalities along the lines of blaschko

Skin Nails Hair Hair:
hypertrichosis

Muscle Soft Tissue:
hypotonia

Chest Breasts:
hypomastia, asymmetric

Clinical features from OMIM®:

300968 (Updated 05-Apr-2021)

Drugs & Therapeutics for Mental Retardation, X-Linked 99, Syndromic, Female-Restricted

Search Clinical Trials , NIH Clinical Center for Mental Retardation, X-Linked 99, Syndromic, Female-Restricted

Genetic Tests for Mental Retardation, X-Linked 99, Syndromic, Female-Restricted

Genetic tests related to Mental Retardation, X-Linked 99, Syndromic, Female-Restricted:

# Genetic test Affiliating Genes
1 Mental Retardation, X-Linked 99, Syndromic, Female-Restricted 29 USP9X

Anatomical Context for Mental Retardation, X-Linked 99, Syndromic, Female-Restricted

MalaCards organs/tissues related to Mental Retardation, X-Linked 99, Syndromic, Female-Restricted:

40
Thyroid, Brain, Eye, Cerebellum, Heart, Breast

Publications for Mental Retardation, X-Linked 99, Syndromic, Female-Restricted

Articles related to Mental Retardation, X-Linked 99, Syndromic, Female-Restricted:

# Title Authors PMID Year
1
De Novo Loss-of-Function Mutations in USP9X Cause a Female-Specific Recognizable Syndrome with Developmental Delay and Congenital Malformations. 57 6
26833328 2016
2
Massively parallel sequencing of patients with intellectual disability, congenital anomalies and/or autism spectrum disorders with a targeted gene panel. 57
24690944 2014
3
Novel USP9X variant associated with syndromic intellectual disability in a female: A case study and review. 61
33638286 2021

Variations for Mental Retardation, X-Linked 99, Syndromic, Female-Restricted

ClinVar genetic disease variations for Mental Retardation, X-Linked 99, Syndromic, Female-Restricted:

6 (show all 16)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 USP9X NM_001039591.3(USP9X):c.3028-2A>G SNV Pathogenic 223095 rs869025589 GRCh37: X:41031089-41031089
GRCh38: X:41171836-41171836
2 USP9X NM_001039591.3(USP9X):c.1111C>T (p.Arg371Ter) SNV Pathogenic 223098 rs869025592 GRCh37: X:41000634-41000634
GRCh38: X:41141381-41141381
3 USP9X NM_001039591.3(USP9X):c.44del (p.Asn15fs) Deletion Pathogenic 547925 rs1555917927 GRCh37: X:40982924-40982924
GRCh38: X:41123671-41123671
4 USP9X NM_001039591.3(USP9X):c.6458dup (p.Ser2153fs) Duplication Pathogenic 984625 GRCh37: X:41078376-41078377
GRCh38: X:41219123-41219124
5 USP9X NM_001039591.3(USP9X):c.6004C>T (p.Arg2002Ter) SNV Pathogenic 984638 GRCh37: X:41075824-41075824
GRCh38: X:41216571-41216571
6 USP9X NM_001039591.3(USP9X):c.4756del (p.Ala1587fs) Deletion Pathogenic 488635 rs1555930128 GRCh37: X:41060465-41060465
GRCh38: X:41201212-41201212
7 USP9X NM_001039591.3(USP9X):c.3763C>T (p.Gln1255Ter) SNV Pathogenic 223097 rs869025591 GRCh37: X:41047323-41047323
GRCh38: X:41188070-41188070
8 USP9X NM_001039591.3(USP9X):c.2554C>T (p.Arg852Ter) SNV Pathogenic 223094 rs869025588 GRCh37: X:41027389-41027389
GRCh38: X:41168136-41168136
9 USP9X NM_001039591.3(USP9X):c.2644_2645insA (p.Arg882fs) Insertion Pathogenic 223096 rs869025590 GRCh37: X:41029255-41029256
GRCh38: X:41170002-41170003
10 USP9X NM_001039591.3(USP9X):c.671T>C (p.Leu224Pro) SNV Likely pathogenic 620023 GRCh37: X:40999925-40999925
GRCh38: X:41140672-41140672
11 USP9X NM_001039591.3(USP9X):c.323-1G>C SNV Likely pathogenic 976276 GRCh37: X:40993977-40993977
GRCh38: X:41134724-41134724
12 USP9X NM_001039591.3(USP9X):c.5047C>T (p.Gln1683Ter) SNV Likely pathogenic 488397 rs1555932766 GRCh37: X:41069793-41069793
GRCh38: X:41210540-41210540
13 USP9X NM_001039591.3(USP9X):c.3304G>A (p.Ala1102Thr) SNV Uncertain significance 548621 rs1555927212 GRCh37: X:41043674-41043674
GRCh38: X:41184421-41184421
14 USP9X NM_001039591.3(USP9X):c.1782C>G (p.Pro594=) SNV Uncertain significance 1028482 GRCh37: X:41012219-41012219
GRCh38: X:41152966-41152966
15 USP9X NM_001039591.3(USP9X):c.4163A>G (p.Asn1388Ser) SNV Uncertain significance 520886 rs369178019 GRCh37: X:41055921-41055921
GRCh38: X:41196668-41196668
16 USP9X NM_001039591.3(USP9X):c.4817A>G (p.Asp1606Gly) SNV Uncertain significance 929458 GRCh37: X:41060526-41060526
GRCh38: X:41201273-41201273

Expression for Mental Retardation, X-Linked 99, Syndromic, Female-Restricted

Search GEO for disease gene expression data for Mental Retardation, X-Linked 99, Syndromic, Female-Restricted.

Pathways for Mental Retardation, X-Linked 99, Syndromic, Female-Restricted

GO Terms for Mental Retardation, X-Linked 99, Syndromic, Female-Restricted

Sources for Mental Retardation, X-Linked 99, Syndromic, Female-Restricted

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