MCID: MNT046
MIFTS: 34

Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia

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

Aliases & Classifications for Mental Retardation and Microcephaly with Pontine and Cerebellar...

MalaCards integrated aliases for Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia:

Name: Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia 57 12 75 29 13 6 73
Micpch 57 12 59 75
Micpch Syndrome 57 75 37
X-Linked Intellectual Disability-Microcephaly-Pontocerebellar Hypoplasia Syndrome 12 59
Syndromic X-Linked Intellectual Disability Najm Type 12 15
Mental Retardation, X-Linked, Syndromic, Najm Type 57 75
Mental Retardation, Cask-Related, X-Linked 29 6
Mrxsna 57 75
Mental Retardation, Microcephaly with Pontine, Cerebellar Hypoplasia 40
Mental Retardation, X-Linked, Syndromic, Najm Type; Mrxsna 57
X-Linked Intellectual Disability, Najm Type 59
Mental Retardation X-Linked with Nystagmus 75
Mental Retardation X-Linked Cask-Related 75
Intellectual Deficit X-Linked Type Najm 75

Characteristics:

Orphanet epidemiological data:

59
x-linked intellectual disability, najm type
Inheritance: X-linked dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

57
Inheritance:
x-linked dominant

Miscellaneous:
onset at birth or early infancy
dysmorphic facial features are variable


HPO:

32
mental retardation and microcephaly with pontine and cerebellar hypoplasia:
Inheritance x-linked dominant inheritance


Classifications:



Summaries for Mental Retardation and Microcephaly with Pontine and Cerebellar...

OMIM : 57 Mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH) is an X-linked disorder affecting females and characterized by severe intellectual disability, microcephaly, and variable degrees of pontocerebellar hypoplasia. Affected individuals have very poor psychomotor development, often without independent ambulation or speech, and axial hypotonia with or without hypertonia. Some may have sensorineural hearing loss or eye anomalies. Dysmorphic features include overall poor growth, severe microcephaly (-3.5 to -10 SD), broad nasal bridge and tip, large ears, long philtrum, micrognathia, and hypertelorism (summary by Moog et al., 2011). (300749)

MalaCards based summary : Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia, also known as micpch, is related to microcephaly and x-linked intellectual disability, najm type, and has symptoms including muscle spasticity and muscle weakness. An important gene associated with Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia is CASK (Calcium/Calmodulin Dependent Serine Protein Kinase), and among its related pathways/superpathways is Neuroscience. Affiliated tissues include eye, cortex and brain, and related phenotypes are hypertelorism and long philtrum

Disease Ontology : 12 A syndromic X-linked intellectual disability characterized by severe intellectual disability, microcephaly with pontine and cerebellar hypoplasia that has material basis in heterozygous mutation or deletion in the CASK gene on chromosome Xp11.

UniProtKB/Swiss-Prot : 75 Mental retardation and microcephaly with pontine and cerebellar hypoplasia: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Affected individuals can manifest a severe phenotype consisting of severe intellectual deficit, congenital or postnatal microcephaly, disproportionate brainstem and cerebellar hypoplasia. A milder phenotype consists of mental retardation alone or associated with nystagmus.

Related Diseases for Mental Retardation and Microcephaly with Pontine and Cerebellar...

Diseases related to Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia via text searches within MalaCards or GeneCards Suite gene sharing:

# Related Disease Score Top Affiliating Genes
1 microcephaly 27.7 CASK POGZ TSEN54
2 x-linked intellectual disability, najm type 11.4
3 cerebellar hypoplasia 10.2
4 mowat-wilson syndrome 9.5 JAKMIP1 POGZ
5 trehalase deficiency 8.1 CASK POGZ TBR1 TSEN54

Graphical network of the top 20 diseases related to Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia:



Diseases related to Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia

Symptoms & Phenotypes for Mental Retardation and Microcephaly with Pontine and Cerebellar...

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
spasticity
hyperreflexia
dilated fourth ventricle
delayed psychomotor development
seizures (less common)
more
Growth Height:
short stature

Skin Nails Hair Skin:
hypohidrosis

Head And Neck Eyes:
large eyes
epicanthal folds
hypertelorism, mild
optic nerve hypoplasia (less common)
optic disc pallor (less common)
more
Head And Neck Ears:
large ears
hearing loss, sensorineural (less common)

Growth Other:
growth retardation, postnatal

Skeletal Spine:
scoliosis (less common)

Muscle Soft Tissue:
muscle weakness
hypotonia

Head And Neck Face:
long philtrum
micrognathia
oval face

Head And Neck Nose:
prominent nasal bridge
broad nasal tip
broad nasal bridge
small nose

Head And Neck Mouth:
high-arched palate

Growth Weight:
low weight

Head And Neck Head:
microcephaly, progressive (-3.5 to -10 sd)


Clinical features from OMIM:

300749

Human phenotypes related to Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia:

59 32 (show all 47)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 hypertelorism 59 32 Frequent (79-30%) HP:0000316
2 long philtrum 59 32 Frequent (79-30%) HP:0000343
3 micrognathia 59 32 Frequent (79-30%) HP:0000347
4 macrotia 59 32 Frequent (79-30%) HP:0000400
5 sensorineural hearing impairment 59 32 occasional (7.5%) Frequent (79-30%) HP:0000407
6 wide nasal bridge 59 32 Frequent (79-30%) HP:0000431
7 strabismus 59 32 occasional (7.5%) Frequent (79-30%) HP:0000486
8 optic nerve hypoplasia 59 32 occasional (7.5%) Occasional (29-5%) HP:0000609
9 nystagmus 59 32 occasional (7.5%) Frequent (79-30%) HP:0000639
10 seizures 59 32 occasional (7.5%) Frequent (79-30%) HP:0001250
11 spasticity 59 32 Occasional (29-5%) HP:0001257
12 cerebellar hypoplasia 59 32 Very frequent (99-80%) HP:0001321
13 absent speech 59 32 Occasional (29-5%) HP:0001344
14 intellectual disability, moderate 59 32 Very frequent (99-80%) HP:0002342
15 scoliosis 59 32 occasional (7.5%) Occasional (29-5%) HP:0002650
16 microcephaly 59 Frequent (79-30%)
17 broad forehead 59 Frequent (79-30%)
18 visual impairment 59 Frequent (79-30%)
19 cataract 59 Frequent (79-30%)
20 myopia 59 Frequent (79-30%)
21 chorioretinal coloboma 59 Occasional (29-5%)
22 optic atrophy 59 Occasional (29-5%)
23 gait disturbance 59 Frequent (79-30%)
24 failure to thrive 59 Occasional (29-5%)
25 rigidity 59 Occasional (29-5%)
26 cerebral cortical atrophy 59 Frequent (79-30%)
27 severe global developmental delay 59 Very frequent (99-80%)
28 high palate 32 HP:0000218
29 progressive microcephaly 32 HP:0000253
30 epicanthus 32 HP:0000286
31 oval face 32 HP:0000300
32 prominent nasal bridge 32 HP:0000426
33 broad nasal tip 32 HP:0000455
34 optic disc pallor 32 occasional (7.5%) HP:0000543
35 hypohidrosis 32 HP:0000966
36 abnormally large globe 32 HP:0001090
37 global developmental delay 32 HP:0001263
38 generalized hypotonia 32 HP:0001290
39 muscle weakness 32 HP:0001324
40 hyperreflexia 32 HP:0001347
41 dilated fourth ventricle 32 HP:0002198
42 short nose 32 HP:0003196
43 short stature 32 HP:0004322
44 decreased body weight 32 HP:0004325
45 macrogyria 32 occasional (7.5%) HP:0007227
46 postnatal growth retardation 32 HP:0008897
47 muscular hypotonia of the trunk 32 HP:0008936

UMLS symptoms related to Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia:


muscle spasticity, muscle weakness

Drugs & Therapeutics for Mental Retardation and Microcephaly with Pontine and Cerebellar...

Search Clinical Trials , NIH Clinical Center for Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia

Genetic Tests for Mental Retardation and Microcephaly with Pontine and Cerebellar...

Genetic tests related to Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia:

# Genetic test Affiliating Genes
1 Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia 29 CASK
2 Mental Retardation, Cask-Related, X-Linked 29

Anatomical Context for Mental Retardation and Microcephaly with Pontine and Cerebellar...

MalaCards organs/tissues related to Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia:

41
Eye, Cortex, Brain

Publications for Mental Retardation and Microcephaly with Pontine and Cerebellar...

Articles related to Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia:

# Title Authors Year
1
Novel intragenic duplications and mutations of CASK in patients with mental retardation and microcephaly with pontine and cerebellar hypoplasia (MICPCH). ( 21735175 )
2012

Variations for Mental Retardation and Microcephaly with Pontine and Cerebellar...

UniProtKB/Swiss-Prot genetic disease variations for Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia:

75
# Symbol AA change Variation ID SNP ID
1 CASK p.Tyr268His VAR_062996 rs137852817
2 CASK p.Pro396Ser VAR_062997 rs137852820
3 CASK p.Asp710Gly VAR_062998 rs137852818

ClinVar genetic disease variations for Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia:

6
(show top 50) (show all 122)
# Gene Variation Type Significance SNP ID Assembly Location
1 CASK NM_003688.3(CASK): c.1915C> T (p.Arg639Ter) single nucleotide variant Pathogenic rs137852815 GRCh37 Chromosome X, 41413096: 41413096
2 CASK NM_003688.3(CASK): c.1915C> T (p.Arg639Ter) single nucleotide variant Pathogenic rs137852815 GRCh38 Chromosome X, 41553843: 41553843
3 CASK NM_003688.3(CASK): c.915G> A (p.Lys305=) single nucleotide variant Pathogenic rs387906499 GRCh37 Chromosome X, 41495831: 41495831
4 CASK NM_003688.3(CASK): c.915G> A (p.Lys305=) single nucleotide variant Pathogenic rs387906499 GRCh38 Chromosome X, 41636578: 41636578
5 CASK NM_003688.3(CASK): c.2168A> G (p.Tyr723Cys) single nucleotide variant Likely pathogenic rs398122844 GRCh37 Chromosome X, 41394199: 41394199
6 CASK NM_003688.3(CASK): c.2168A> G (p.Tyr723Cys) single nucleotide variant Likely pathogenic rs398122844 GRCh38 Chromosome X, 41534946: 41534946
7 CASK NM_003688.3(CASK): c.316C> T (p.Arg106Ter) single nucleotide variant Pathogenic rs387906704 GRCh37 Chromosome X, 41604817: 41604817
8 CASK NM_003688.3(CASK): c.316C> T (p.Arg106Ter) single nucleotide variant Pathogenic rs387906704 GRCh38 Chromosome X, 41745564: 41745564
9 CASK NG_016754.1: g.5000-?_5105+?del deletion Pathogenic
10 CASK NM_003688.3(CASK): c.1639C> T (p.Gln547Ter) single nucleotide variant Pathogenic rs387906705 GRCh37 Chromosome X, 41420841: 41420841
11 CASK NM_003688.3(CASK): c.1639C> T (p.Gln547Ter) single nucleotide variant Pathogenic rs387906705 GRCh38 Chromosome X, 41561588: 41561588
12 CASK NM_003688.3(CASK): c.1269C> T (p.Asn423=) single nucleotide variant Uncertain significance rs17315800 GRCh37 Chromosome X, 41446205: 41446205
13 CASK NM_003688.3(CASK): c.1269C> T (p.Asn423=) single nucleotide variant Uncertain significance rs17315800 GRCh38 Chromosome X, 41586952: 41586952
14 CASK NM_003688.3(CASK): c.1644_1645delAG (p.Val549Glyfs) deletion Pathogenic rs587783357 GRCh37 Chromosome X, 41420835: 41420836
15 CASK NM_003688.3(CASK): c.1644_1645delAG (p.Val549Glyfs) deletion Pathogenic rs587783357 GRCh38 Chromosome X, 41561582: 41561583
16 CASK NM_003688.3(CASK): c.2039G> C (p.Trp680Ser) single nucleotide variant Uncertain significance rs587783358 GRCh37 Chromosome X, 41412972: 41412972
17 CASK NM_003688.3(CASK): c.2039G> C (p.Trp680Ser) single nucleotide variant Uncertain significance rs587783358 GRCh38 Chromosome X, 41553719: 41553719
18 CASK NM_003688.3(CASK): c.2040-9A> G single nucleotide variant Benign/Likely benign rs138290714 GRCh37 Chromosome X, 41402068: 41402068
19 CASK NM_003688.3(CASK): c.2040-9A> G single nucleotide variant Benign/Likely benign rs138290714 GRCh38 Chromosome X, 41542815: 41542815
20 CASK NM_003688.3(CASK): c.2041C> T (p.Arg681Ter) single nucleotide variant Pathogenic rs587783360 GRCh37 Chromosome X, 41402058: 41402058
21 CASK NM_003688.3(CASK): c.2041C> T (p.Arg681Ter) single nucleotide variant Pathogenic rs587783360 GRCh38 Chromosome X, 41542805: 41542805
22 CASK NM_003688.3(CASK): c.2074C> T (p.Gln692Ter) single nucleotide variant Pathogenic rs587783361 GRCh37 Chromosome X, 41402025: 41402025
23 CASK NM_003688.3(CASK): c.2074C> T (p.Gln692Ter) single nucleotide variant Pathogenic rs587783361 GRCh38 Chromosome X, 41542772: 41542772
24 CASK NM_003688.3(CASK): c.20_27delTGTTCGAG (p.Leu7Argfs) deletion Pathogenic rs587783362 GRCh37 Chromosome X, 41782215: 41782222
25 CASK NM_003688.3(CASK): c.20_27delTGTTCGAG (p.Leu7Argfs) deletion Pathogenic rs587783362 GRCh38 Chromosome X, 41922962: 41922969
26 CASK NM_003688.3(CASK): c.2427G> A (p.Ala809=) single nucleotide variant Conflicting interpretations of pathogenicity rs141158465 GRCh37 Chromosome X, 41390338: 41390338
27 CASK NM_003688.3(CASK): c.2427G> A (p.Ala809=) single nucleotide variant Conflicting interpretations of pathogenicity rs141158465 GRCh38 Chromosome X, 41531085: 41531085
28 CASK NM_003688.3(CASK): c.2470C> T (p.Gln824Ter) single nucleotide variant Pathogenic rs587783364 GRCh37 Chromosome X, 41390295: 41390295
29 CASK NM_003688.3(CASK): c.2470C> T (p.Gln824Ter) single nucleotide variant Pathogenic rs587783364 GRCh38 Chromosome X, 41531042: 41531042
30 CASK NM_003688.3(CASK): c.430-2A> T single nucleotide variant Pathogenic rs587783366 GRCh37 Chromosome X, 41530785: 41530785
31 CASK NM_003688.3(CASK): c.430-2A> T single nucleotide variant Pathogenic rs587783366 GRCh38 Chromosome X, 41671532: 41671532
32 CASK NM_003688.3(CASK): c.617G> A (p.Gly206Asp) single nucleotide variant Uncertain significance rs587783367 GRCh37 Chromosome X, 41524621: 41524621
33 CASK NM_003688.3(CASK): c.617G> A (p.Gly206Asp) single nucleotide variant Uncertain significance rs587783367 GRCh38 Chromosome X, 41665368: 41665368
34 CASK NM_003688.3(CASK): c.708+1G> A single nucleotide variant Pathogenic rs587783368 GRCh37 Chromosome X, 41524529: 41524529
35 CASK NM_003688.3(CASK): c.708+1G> A single nucleotide variant Pathogenic rs587783368 GRCh38 Chromosome X, 41665276: 41665276
36 CASK NM_003688.3(CASK): c.764G> A (p.Arg255His) single nucleotide variant Likely pathogenic rs587783369 GRCh37 Chromosome X, 41519759: 41519759
37 CASK NM_003688.3(CASK): c.764G> A (p.Arg255His) single nucleotide variant Likely pathogenic rs587783369 GRCh38 Chromosome X, 41660506: 41660506
38 CASK NM_003688.3(CASK): c.82C> T (p.Arg28Ter) single nucleotide variant Pathogenic rs587783370 GRCh37 Chromosome X, 41712458: 41712458
39 CASK NM_003688.3(CASK): c.82C> T (p.Arg28Ter) single nucleotide variant Pathogenic rs587783370 GRCh38 Chromosome X, 41853205: 41853205
40 CASK NM_003688.3(CASK): c.880C> T (p.Gln294Ter) single nucleotide variant Pathogenic rs587783371 GRCh37 Chromosome X, 41495866: 41495866
41 CASK NM_003688.3(CASK): c.880C> T (p.Gln294Ter) single nucleotide variant Pathogenic rs587783371 GRCh38 Chromosome X, 41636613: 41636613
42 CASK NM_003688.3(CASK): c.1922G> A (p.Arg641Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs76106850 GRCh37 Chromosome X, 41413089: 41413089
43 CASK NM_003688.3(CASK): c.1922G> A (p.Arg641Lys) single nucleotide variant Conflicting interpretations of pathogenicity rs76106850 GRCh38 Chromosome X, 41553836: 41553836
44 CASK NM_003688.3(CASK): c.891A> G (p.Lys297=) single nucleotide variant Conflicting interpretations of pathogenicity rs544979992 GRCh37 Chromosome X, 41495855: 41495855
45 CASK NM_003688.3(CASK): c.891A> G (p.Lys297=) single nucleotide variant Conflicting interpretations of pathogenicity rs544979992 GRCh38 Chromosome X, 41636602: 41636602
46 CASK NM_003688.3(CASK): c.55G> A (p.Gly19Arg) single nucleotide variant Likely pathogenic rs727503840 GRCh37 Chromosome X, 41782187: 41782187
47 CASK NM_003688.3(CASK): c.55G> A (p.Gly19Arg) single nucleotide variant Likely pathogenic rs727503840 GRCh38 Chromosome X, 41922934: 41922934
48 CASK NM_003688.3(CASK): c.1976G> A (p.Gly659Asp) single nucleotide variant Pathogenic rs727505397 GRCh37 Chromosome X, 41413035: 41413035
49 CASK NM_003688.3(CASK): c.1976G> A (p.Gly659Asp) single nucleotide variant Pathogenic rs727505397 GRCh38 Chromosome X, 41553782: 41553782
50 CASK NM_003688.3(CASK): c.79C> T (p.Arg27Ter) single nucleotide variant Pathogenic rs794727270 GRCh37 Chromosome X, 41712461: 41712461

Expression for Mental Retardation and Microcephaly with Pontine and Cerebellar...

Search GEO for disease gene expression data for Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia.

Pathways for Mental Retardation and Microcephaly with Pontine and Cerebellar...

Pathways related to Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1 11.16 CASK TBR1

GO Terms for Mental Retardation and Microcephaly with Pontine and Cerebellar...

Sources for Mental Retardation and Microcephaly with Pontine and Cerebellar...

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 ExPASy
19 FMA
28 GO
29 GTR
30 HGMD
31 HMDB
32 HPO
33 ICD10
34 ICD10 via Orphanet
35 ICD9CM
36 IUPHAR
37 KEGG
38 LifeMap
40 LOVD
42 MedGen
44 MeSH
45 MESH via Orphanet
46 MGI
49 NCI
50 NCIt
51 NDF-RT
54 NINDS
55 Novoseek
57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 SNOMED-CT via Orphanet
71 TGDB
72 Tocris
73 UMLS
74 UMLS via Orphanet
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