MRXSO
MCID: MNT229
MIFTS: 43

Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance (MRXSO)

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

Aliases & Classifications for Mental Retardation, X-Linked, with Cerebellar Hypoplasia and...

MalaCards integrated aliases for Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance:

Name: Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance 57 13
Mental Retardation X-Linked with Cerebellar Hypoplasia and Distinctive Facial Appearance 72 29 6
X-Linked Mental Retardation with Cerebellar Hypoplasia and Distinctive Facial Appearance 12 15
Mental Retardation, X-Linked, with Cerebellar Hypoplasia, Distinctive Facial Appearance 39
X-Linked Intellectual Disability-Cerebellar Hypoplasia Syndrome 58
Mental Retardation, X-Linked 60, Formerly; Mrx60, Formerly 57
Mental Retardation, X-Linked, Syndromic, Ophn1-Related 72
Mental Retardation, X-Linked 60, Formerly 57
Mental Retardation X-Linked 60 72
Oligophrenin-1 Syndrome 58
Mrx60, Formerly 57
Ophn1 Syndrome 58
Mrx60 72
Mrxso 72

Characteristics:

Orphanet epidemiological data:

58
x-linked intellectual disability-cerebellar hypoplasia syndrome
Inheritance: X-linked dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM®:

57 (Updated 05-Apr-2021)
Miscellaneous:
onset in infancy
most carrier females have mild mental retardation and subtle facial changes

Inheritance:
x-linked recessive


HPO:

31
mental retardation, x-linked, with cerebellar hypoplasia and distinctive facial appearance:
Onset and clinical course infantile onset
Inheritance x-linked recessive inheritance


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


Summaries for Mental Retardation, X-Linked, with Cerebellar Hypoplasia and...

UniProtKB/Swiss-Prot : 72 Mental retardation, X-linked, syndromic, OPHN1-related: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. MRXSO patients manifest mental retardation associated with cerebellar hypoplasia and distinctive facial dysmorphism.

MalaCards based summary : Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance, also known as mental retardation x-linked with cerebellar hypoplasia and distinctive facial appearance, is related to ophn1 syndrome and coenzyme q10 deficiency, primary, 3. An important gene associated with Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance is OPHN1 (Oligophrenin 1), and among its related pathways/superpathways are Spinocerebellar ataxia and Ubiquinol biosynthesis. Affiliated tissues include brain and eye, and related phenotypes are intellectual disability and global developmental delay

Disease Ontology : 12 A syndromic X-linked intellectual disability characterized by neonatal hypotonia with motor delay but no obvious ataxia, marked strabismus, early-onset complex partial seizures, and moderate to severe mental retardation and has material basis in mutation in the oligophrenin-1 gene.

More information from OMIM: 300486 PS309510

Related Diseases for Mental Retardation, X-Linked, with Cerebellar Hypoplasia and...

Diseases related to Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 67)
# Related Disease Score Top Affiliating Genes
1 ophn1 syndrome 11.5
2 coenzyme q10 deficiency, primary, 3 10.2 PDSS1 COQ9
3 christianson syndrome 10.2 SLC9A7 SLC9A6
4 cerebral creatine deficiency syndrome 1 10.2 SLC9A7 SLC9A6 OPHN1
5 leigh syndrome with nephrotic syndrome 10.2 COQ8A COQ2
6 spastic paraplegia 7, autosomal recessive 10.1 COQ8A APTX
7 coenzyme q10 deficiency, primary, 6 10.1 PDSS1 COQ9 COQ8A
8 coenzyme q10 deficiency, primary, 1 10.1 COQ8A COQ2 APTX
9 epileptic encephalopathy, childhood-onset 10.1 SLC9A7 CACNA1A
10 vestibular nystagmus 10.0 CACNA1A APTX
11 spinocerebellar degeneration 10.0 ATXN3 ATXN2
12 spinocerebellar ataxia, autosomal recessive 14 10.0 COQ8A CACNA1A
13 coenzyme q10 deficiency, primary, 5 10.0 PDSS1 COQ9 COQ8A COQ2
14 coenzyme q10 deficiency, primary, 7 10.0 PDSS1 COQ9 COQ8A COQ2
15 coenzyme q10 deficiency, primary, 4 10.0 PDSS1 COQ9 COQ8A APTX
16 episodic ataxia, type 6 10.0 CACNA1A ATXN7
17 mitochondrial encephalomyopathy 9.9 PDSS1 COQ9 COQ8A COQ2
18 spinocerebellar ataxia 30 9.9 CACNA1A ATXN7
19 pontocerebellar hypoplasia, type 7 9.9 CACNA1A APTX
20 cardiofaciocutaneous syndrome 1 9.9 PDSS1 COQ8A COQ2 APTX
21 spinocerebellar ataxia 14 9.9 CACNA1A APTX
22 spastic ataxia, charlevoix-saguenay type 9.9 FXN APTX
23 mutism 9.9 SLC9A6 FMR1
24 spinocerebellar ataxia, autosomal recessive 8 9.9 COQ8A CACNA1A ATXN7
25 anemia, sideroblastic, and spinocerebellar ataxia 9.8 FXN ABCB7
26 ataxia with vitamin 3 deficiency 9.8 FXN APTX
27 spinocerebellar ataxia 7 9.8 ATXN7 ATXN3 ATXN2
28 spinocerebellar ataxia 8 9.8 FMR1 ATXN7 ATXN2
29 coenzyme q10 deficiency disease 9.8 PDSS1 COQ9 COQ8A COQ2 APTX
30 multiple acyl-coa dehydrogenase deficiency 9.8 PDSS1 COQ9 COQ8A COQ2 APTX
31 marinesco-sjogren syndrome 9.8 FXN COQ8A APTX
32 olivopontocerebellar atrophy 9.8 CACNA1A ATXN7 ATXN2
33 mitochondrial dna depletion syndrome 7 9.8 FXN APTX
34 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 9.7 PDSS1 COQ9 COQ2
35 x-linked hereditary ataxia 9.6 FXN FMR1 ATXN7
36 mitochondrial complex i deficiency, nuclear type 1 9.6 FXN COQ9 COQ8A COQ2
37 spinocerebellar ataxia, autosomal recessive, with axonal neuropathy 2 9.6 FXN CACNA1A APTX
38 aceruloplasminemia 9.6 FXN COQ8A CACNA1A
39 spinocerebellar ataxia 12 9.5 CACNA1A ATXN7 ATXN3 ATXN2
40 spinocerebellar ataxia 17 9.5 CACNA1A ATXN7 ATXN3 ATXN2
41 spinocerebellar ataxia 2 9.5 CACNA1A ATXN7 ATXN3 ATXN2
42 machado-joseph disease 9.5 CACNA1A ATXN7 ATXN3 ATXN2
43 contractures, pterygia, and spondylocarpotarsal fusion syndrome 1a 9.5 CACNA1A ATXN7 ATXN3 ATXN2
44 huntington disease-like 2 9.5 FMR1 CACNA1A ATXN7 ATXN3
45 ataxia, early-onset, with oculomotor apraxia and hypoalbuminemia 9.5 FXN COQ8A CACNA1A APTX
46 leigh syndrome 9.5 PDSS1 FXN COQ9 COQ8A COQ2
47 spastic ataxia 9.5 FXN COQ8A CACNA1A APTX
48 movement disease 9.4 FMR1 CACNA1A ATXN3 ATXN2
49 fragile x-associated tremor/ataxia syndrome 9.4 FXN FMR1 ATXN7 ATXN2
50 dementia 9.4 FMR1 CACNA1A ATXN3 ATXN2

Graphical network of the top 20 diseases related to Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance:



Diseases related to Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance

Symptoms & Phenotypes for Mental Retardation, X-Linked, with Cerebellar Hypoplasia and...

Human phenotypes related to Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance:

58 31 (show top 50) (show all 55)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 intellectual disability 58 31 Very frequent (99-80%) HP:0001249
2 global developmental delay 58 31 Very frequent (99-80%) HP:0001263
3 mandibular prognathia 58 31 Occasional (29-5%) HP:0000303
4 strabismus 58 31 Frequent (79-30%) HP:0000486
5 deeply set eye 58 31 Frequent (79-30%) HP:0000490
6 cerebellar hypoplasia 58 31 Very frequent (99-80%) HP:0001321
7 generalized hypotonia 58 31 Frequent (79-30%) HP:0001290
8 retrocerebellar cyst 58 31 Occasional (29-5%) HP:0006951
9 enlarged cisterna magna 58 31 Occasional (29-5%) HP:0002280
10 macrocephaly 31 HP:0000256
11 spasticity 31 HP:0001257
12 frontal bossing 31 HP:0002007
13 neurological speech impairment 58 Frequent (79-30%)
14 nystagmus 31 HP:0000639
15 ataxia 58 Frequent (79-30%)
16 muscular hypotonia 58 Frequent (79-30%)
17 prominent supraorbital ridges 31 HP:0000336
18 macrotia 31 HP:0000400
19 wide nasal bridge 58 Occasional (29-5%)
20 delayed speech and language development 31 HP:0000750
21 abnormal facial shape 58 Frequent (79-30%)
22 intellectual disability, severe 58 Frequent (79-30%)
23 prominent forehead 31 HP:0011220
24 cryptorchidism 31 HP:0000028
25 attention deficit hyperactivity disorder 58 Occasional (29-5%)
26 generalized myoclonic seizures 58 Frequent (79-30%)
27 micropenis 31 HP:0000054
28 thin upper lip vermilion 31 HP:0000219
29 long face 31 HP:0000276
30 ventriculomegaly 58 Frequent (79-30%)
31 intellectual disability, moderate 58 Frequent (79-30%)
32 short philtrum 31 HP:0000322
33 hypotelorism 31 HP:0000601
34 long nose 31 HP:0003189
35 gait ataxia 31 HP:0002066
36 scrotal hypoplasia 31 HP:0000046
37 poor eye contact 58 Frequent (79-30%)
38 focal impaired awareness seizure 58 Frequent (79-30%)
39 prominent nose 58 Occasional (29-5%)
40 autistic behavior 58 Frequent (79-30%)
41 hyperactivity 31 HP:0000752
42 frontal cortical atrophy 58 Occasional (29-5%)
43 intention tremor 58 Occasional (29-5%)
44 poor speech 58 Frequent (79-30%)
45 postural instability 58 Occasional (29-5%)
46 aplasia/hypoplasia of the cerebellar vermis 58 Occasional (29-5%)
47 impaired social interactions 58 Frequent (79-30%)
48 partial absence of cerebellar vermis 58 Frequent (79-30%)
49 tall chin 58 Frequent (79-30%)
50 caudate atrophy 58 Occasional (29-5%)

Symptoms via clinical synopsis from OMIM®:

57 (Updated 05-Apr-2021)
Head And Neck Head:
macrocephaly

Head And Neck Eyes:
nystagmus
strabismus
hypotelorism
deep-set eyes

Genitourinary Internal Genitalia Male:
cryptorchidism

Genitourinary External Genitalia Male:
microphallus
hypoplastic scrotum

Head And Neck Ears:
large ears

Neurologic Central Nervous System:
seizures
spasticity
cerebellar hypoplasia
retrocerebellar cyst
enlarged cisterna magna
more
Head And Neck Face:
prominent supraorbital ridges
prominent forehead
long face
short philtrum
prominent chin
more
Neurologic Behavioral Psychiatric Manifestations:
hyperactivity
autistic features

Head And Neck Mouth:
thin upper lip

Head And Neck Nose:
long, tubular nose

Clinical features from OMIM®:

300486 (Updated 05-Apr-2021)

MGI Mouse Phenotypes related to Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance:

46
# Description MGI Source Accession Score Top Affiliating Genes
1 behavior/neurological MP:0005386 9.9 ATXN2 ATXN3 ATXN7 CACNA1A COQ8A COQ9
2 mortality/aging MP:0010768 9.7 ABCB7 ATXN2 ATXN7 CACNA1A COQ2 COQ9
3 nervous system MP:0003631 9.4 ABCB7 ATXN2 ATXN3 ATXN7 CACNA1A COQ8A

Drugs & Therapeutics for Mental Retardation, X-Linked, with Cerebellar Hypoplasia and...

Search Clinical Trials , NIH Clinical Center for Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance

Genetic Tests for Mental Retardation, X-Linked, with Cerebellar Hypoplasia and...

Genetic tests related to Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance:

# Genetic test Affiliating Genes
1 Mental Retardation X-Linked with Cerebellar Hypoplasia and Distinctive Facial Appearance 29 OPHN1

Anatomical Context for Mental Retardation, X-Linked, with Cerebellar Hypoplasia and...

MalaCards organs/tissues related to Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance:

40
Brain, Eye

Publications for Mental Retardation, X-Linked, with Cerebellar Hypoplasia and...

Articles related to Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance:

# Title Authors PMID Year
1
Novel intragenic deletion in OPHN1 in a family causing XLMR with cerebellar hypoplasia and distinctive facial appearance. 57 6
20528889 2011
2
Delineation of the clinical phenotype associated with OPHN1 mutations based on the clinical and neuropsychological evaluation of three families. 57 6
16158428 2005
3
Oligophrenin 1 (OPHN1) gene mutation causes syndromic X-linked mental retardation with epilepsy, rostral ventricular enlargement and cerebellar hypoplasia. 6 57
12805098 2003
4
Mutations in the oligophrenin-1 gene (OPHN1) cause X linked congenital cerebellar hypoplasia. 57 6
12807966 2003
5
Oligophrenin-1 encodes a rhoGAP protein involved in X-linked mental retardation. 6 57
9582072 1998
6
Loss of X-linked mental retardation gene oligophrenin1 in mice impairs spatial memory and leads to ventricular enlargement and dendritic spine immaturity. 57
17728457 2007
7
Oligophrenin 1 mutations frequently cause X-linked mental retardation with cerebellar hypoplasia. 57
16221952 2005
8
Specific clinical and brain MRI features in mentally retarded patients with mutations in the Oligophrenin-1 gene. 57
14735583 2004
9
Mapping of the X-breakpoint involved in a balanced X;12 translocation in a female with mild mental retardation. 57
9195162 1997
10
Rho Kinase Inhibition Is Essential During In Vitro Neurogenesis and Promotes Phenotypic Rescue of Human Induced Pluripotent Stem Cell-Derived Neurons With Oligophrenin-1 Loss of Function. 61
27160703 2016

Variations for Mental Retardation, X-Linked, with Cerebellar Hypoplasia and...

ClinVar genetic disease variations for Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance:

6 (show all 23)
# Gene Name Type Significance ClinVarId dbSNP ID Position
1 OPHN1 NM_002547.3(OPHN1):c.1579del (p.Ile527fs) Deletion Pathogenic 11577 rs1569211016 GRCh37: X:67316819-67316819
GRCh38: X:68096977-68096977
2 OPHN1 NM_002547.3(OPHN1):c.184C>T (p.Gln62Ter) SNV Pathogenic 11579 rs137854493 GRCh37: X:67518909-67518909
GRCh38: X:68299067-68299067
3 OPHN1 OPHN1, 17.6-KB DEL Deletion Pathogenic 11580 GRCh37:
GRCh38:
4 OPHN1 NG_008960.1:g.224486-?_245539+?del Deletion Pathogenic 29934 GRCh37:
GRCh38:
5 OPHN1 NM_002547.3(OPHN1):c.1138+1G>A SNV Pathogenic 804020 rs1602226670 GRCh37: X:67414306-67414306
GRCh38: X:68194464-68194464
6 OPHN1 NM_002547.3(OPHN1):c.745_752dup (p.Lys251fs) Duplication Pathogenic 11578 rs1569243931 GRCh37: X:67430074-67430075
GRCh38: X:68210232-68210233
7 OPHN1 NM_002547.3(OPHN1):c.642_643TG[1] (p.Val215fs) Microsatellite Pathogenic 11581 rs1569244467 GRCh37: X:67432007-67432008
GRCh38: X:68212165-68212166
8 OPHN1 NM_002547.3(OPHN1):c.496C>T (p.Gln166Ter) SNV Pathogenic 159477 rs587784234 GRCh37: X:67433805-67433805
GRCh38: X:68213963-68213963
9 OPHN1 NM_002547.3(OPHN1):c.1105-13_1109del Deletion Likely pathogenic 992999 GRCh37: X:67414336-67414353
GRCh38: X:68194494-68194511
10 OPHN1 NM_002547.3(OPHN1):c.2035G>A (p.Asp679Asn) SNV Likely pathogenic 224098 rs869312676 GRCh37: X:67283819-67283819
GRCh38: X:68063977-68063977
11 OPHN1 NM_002547.3(OPHN1):c.116_127del (p.Val39_Asp42del) Deletion Likely pathogenic 995998 GRCh37: X:67652736-67652747
GRCh38: X:68432894-68432905
12 OPHN1 NM_002547.3(OPHN1):c.1361G>A (p.Arg454Lys) SNV Likely pathogenic 636256 rs1602169116 GRCh37: X:67339090-67339090
GRCh38: X:68119248-68119248
13 OPHN1 NM_002547.3(OPHN1):c.702+11A>C SNV Uncertain significance 159478 rs375325266 GRCh37: X:67431939-67431939
GRCh38: X:68212097-68212097
14 OPHN1 NM_002547.3(OPHN1):c.1201+3A>G SNV Uncertain significance 1029460 GRCh37: X:67413729-67413729
GRCh38: X:68193887-68193887
15 OPHN1 NM_002547.3(OPHN1):c.1889C>A (p.Pro630His) SNV Uncertain significance 1029461 GRCh37: X:67283965-67283965
GRCh38: X:68064123-68064123
16 OPHN1 NM_002547.3(OPHN1):c.215T>C (p.Ile72Thr) SNV Uncertain significance 437438 rs763066236 GRCh37: X:67518878-67518878
GRCh38: X:68299036-68299036
17 OPHN1 NM_002547.3(OPHN1):c.2168A>G (p.Asp723Gly) SNV Uncertain significance 437439 rs374431961 GRCh37: X:67273643-67273643
GRCh38: X:68053801-68053801
18 OPHN1 NM_002547.3(OPHN1):c.1343C>T (p.Ser448Phe) SNV Uncertain significance 812190 GRCh37: X:67339108-67339108
GRCh38: X:68119266-68119266
19 OPHN1 NM_002547.3(OPHN1):c.2129C>T (p.Ala710Val) SNV Uncertain significance 995997 GRCh37: X:67283725-67283725
GRCh38: X:68063883-68063883
20 OPHN1 NM_002547.3(OPHN1):c.1613A>G (p.Asp538Gly) SNV Uncertain significance 211791 rs141368794 GRCh37: X:67316785-67316785
GRCh38: X:68096943-68096943
21 OPHN1 NM_002547.3(OPHN1):c.191T>C (p.Leu64Pro) SNV Uncertain significance 976257 GRCh37: X:67518902-67518902
GRCh38: X:68299060-68299060
22 OPHN1 NM_002547.3(OPHN1):c.2159-4C>T SNV Uncertain significance 159476 rs587784233 GRCh37: X:67273656-67273656
GRCh38: X:68053814-68053814
23 OPHN1 NM_002547.3(OPHN1):c.902C>T (p.Thr301Met) SNV Likely benign 159480 rs138108344 GRCh37: X:67426446-67426446
GRCh38: X:68206604-68206604

Expression for Mental Retardation, X-Linked, with Cerebellar Hypoplasia and...

Search GEO for disease gene expression data for Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance.

Pathways for Mental Retardation, X-Linked, with Cerebellar Hypoplasia and...

Pathways related to Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.29 CACNA1A ATXN3 ATXN2
2
Show member pathways
9.88 PDSS1 COQ9 COQ2

GO Terms for Mental Retardation, X-Linked, with Cerebellar Hypoplasia and...

Cellular components related to Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.17 SLC9A6 PDSS1 FXN COQ9 COQ8A COQ2
2 presynapse GO:0098793 9.13 OPHN1 FMR1 CACNA1A

Biological processes related to Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 regulation of intracellular pH GO:0051453 9.32 SLC9A7 SLC9A6
2 sodium ion import across plasma membrane GO:0098719 9.26 SLC9A7 SLC9A6
3 regulation of pH GO:0006885 9.16 SLC9A7 SLC9A6
4 isoprenoid biosynthetic process GO:0008299 8.96 PDSS1 COQ2
5 ubiquinone biosynthetic process GO:0006744 8.92 PDSS1 COQ9 COQ8A COQ2

Molecular functions related to Mental Retardation, X-Linked, with Cerebellar Hypoplasia and Distinctive Facial Appearance according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 solute:proton antiporter activity GO:0015299 9.26 SLC9A7 SLC9A6
2 prenyltransferase activity GO:0004659 9.16 PDSS1 COQ2
3 sodium:proton antiporter activity GO:0015385 8.96 SLC9A7 SLC9A6
4 potassium:proton antiporter activity GO:0015386 8.62 SLC9A7 SLC9A6

Sources for Mental Retardation, X-Linked, with Cerebellar Hypoplasia and...

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
Content
Loading form....