MCID: MNT046
MIFTS: 34

Mental Retardation and Microcephaly with Pontine and Cerebellar Hypoplasia

Categories: Genetic diseases, Mental diseases, Neuronal diseases, Fetal diseases, Rare 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 53 12 71 28 13 69
Micpch 53 12 55 71
Micpch Syndrome 53 71 36
X-Linked Intellectual Disability-Microcephaly-Pontocerebellar Hypoplasia Syndrome 12 55
Syndromic X-Linked Intellectual Disability Najm Type 12 14
Mental Retardation, X-Linked, Syndromic, Najm Type 53 71
Mrxsna 53 71
Mental Retardation, X-Linked, Syndromic, Najm Type; Mrxsna 53
X-Linked Intellectual Disability, Najm Type 55
Mental Retardation X-Linked with Nystagmus 71
Mental Retardation, Cask-Related, X-Linked 28
Mental Retardation X-Linked Cask-Related 71
Intellectual Deficit X-Linked Type Najm 71

Characteristics:

Orphanet epidemiological data:

55
x-linked intellectual disability, najm type
Inheritance: X-linked dominant; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;

OMIM:

53
Inheritance:
x-linked dominant

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


HPO:

31
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 : 53 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 seizures, hypertelorism and nystagmus. 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, brain and cortex.

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 : 71 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 28.9 CASK POGZ TSEN54
2 x-linked intellectual disability, najm type 11.4
3 cerebellar hypoplasia 10.2
4 mowat-wilson syndrome 9.7 JAKMIP1 POGZ
5 glycine encephalopathy 9.5 JAKMIP1 POGZ

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:

53
MuscleSoftTissue:
muscle weakness
hypotonia

GrowthHeight:
short stature

SkinNailsHairSkin:
hypohidrosis

HeadAndNeckEyes:
large eyes
epicanthal folds
hypertelorism, mild
optic nerve hypoplasia (less common)
optic disc pallor (less common)
more
HeadAndNeckEars:
large ears
hearing loss, sensorineural (less common)

GrowthOther:
growth retardation, postnatal

SkeletalSpine:
scoliosis (less common)

NeurologicCentralNervousSystem:
spasticity
hyperreflexia
delayed psychomotor development
seizures (less common)
mental retardation, moderate to severe
more
HeadAndNeckFace:
long philtrum
micrognathia
oval face

HeadAndNeckNose:
prominent nasal bridge
broad nasal tip
broad nasal bridge
small nose

HeadAndNeckMouth:
high-arched palate

GrowthWeight:
low weight

HeadAndNeckHead:
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:

55 31 (show all 47)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 55 31 occasional (7.5%) Frequent (79-30%) HP:0001250
2 hypertelorism 55 31 Frequent (79-30%) HP:0000316
3 nystagmus 55 31 occasional (7.5%) Frequent (79-30%) HP:0000639
4 spasticity 55 31 Occasional (29-5%) HP:0001257
5 scoliosis 55 31 occasional (7.5%) Occasional (29-5%) HP:0002650
6 macrotia 55 31 Frequent (79-30%) HP:0000400
7 wide nasal bridge 55 31 Frequent (79-30%) HP:0000431
8 microcephaly 55 31 Frequent (79-30%) HP:0000252
9 sensorineural hearing impairment 55 31 occasional (7.5%) Frequent (79-30%) HP:0000407
10 long philtrum 55 31 Frequent (79-30%) HP:0000343
11 micrognathia 55 31 Frequent (79-30%) HP:0000347
12 strabismus 55 31 occasional (7.5%) Frequent (79-30%) HP:0000486
13 absent speech 55 31 Occasional (29-5%) HP:0001344
14 optic nerve hypoplasia 55 31 occasional (7.5%) Occasional (29-5%) HP:0000609
15 cerebellar hypoplasia 55 31 Very frequent (99-80%) HP:0001321
16 intellectual disability, moderate 55 31 Very frequent (99-80%) HP:0002342
17 muscle weakness 31 HP:0001324
18 high palate 31 HP:0000218
19 gait disturbance 55 Frequent (79-30%)
20 hyperreflexia 31 HP:0001347
21 failure to thrive 55 Occasional (29-5%)
22 cataract 55 Frequent (79-30%)
23 global developmental delay 31 HP:0001263
24 short nose 31 HP:0003196
25 visual impairment 55 Frequent (79-30%)
26 optic atrophy 55 Occasional (29-5%)
27 short stature 31 HP:0004322
28 epicanthus 31 HP:0000286
29 severe global developmental delay 55 Very frequent (99-80%)
30 hypohidrosis 31 HP:0000966
31 postnatal growth retardation 31 HP:0008897
32 myopia 55 Frequent (79-30%)
33 cerebral cortical atrophy 55 Frequent (79-30%)
34 prominent nasal bridge 31 HP:0000426
35 broad forehead 55 Frequent (79-30%)
36 chorioretinal coloboma 55 Occasional (29-5%)
37 rigidity 55 Occasional (29-5%)
38 broad nasal tip 31 HP:0000455
39 decreased body weight 31 HP:0004325
40 optic disc pallor 31 occasional (7.5%) HP:0000543
41 generalized hypotonia 31 HP:0001290
42 macrogyria 31 occasional (7.5%) HP:0007227
43 oval face 31 HP:0000300
44 muscular hypotonia of the trunk 31 HP:0008936
45 progressive microcephaly 31 HP:0000253
46 dilated fourth ventricle 31 HP:0002198
47 abnormally large globe 31 HP:0001090

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


muscle weakness, muscle spasticity

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 28 CASK
2 Mental Retardation, Cask-Related, X-Linked 28

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:

38
Eye, Brain, Cortex

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:

71
# 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 all 29)
# 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.915G> A (p.Lys305=) single nucleotide variant Pathogenic rs387906499 GRCh37 Chromosome X, 41495831: 41495831
3 CASK NM_003688.3(CASK): c.2168A> G (p.Tyr723Cys) single nucleotide variant Pathogenic/Likely pathogenic rs398122844 GRCh37 Chromosome X, 41394199: 41394199
4 CASK NM_003688.3(CASK): c.316C> T (p.Arg106Ter) single nucleotide variant Pathogenic rs387906704 GRCh37 Chromosome X, 41604817: 41604817
5 CASK NG_016754.1: g.5000-?_5105+?del deletion Pathogenic
6 CASK NM_003688.3(CASK): c.1639C> T (p.Gln547Ter) single nucleotide variant Pathogenic rs387906705 GRCh37 Chromosome X, 41420841: 41420841
7 CASK NM_003688.3(CASK): c.1644_1645delAG (p.Val549Glyfs) deletion Pathogenic rs587783357 GRCh38 Chromosome X, 41561582: 41561583
8 CASK NM_003688.3(CASK): c.2041C> T (p.Arg681Ter) single nucleotide variant Pathogenic rs587783360 GRCh38 Chromosome X, 41542805: 41542805
9 CASK NM_003688.3(CASK): c.2074C> T (p.Gln692Ter) single nucleotide variant Pathogenic rs587783361 GRCh38 Chromosome X, 41542772: 41542772
10 CASK NM_003688.3(CASK): c.20_27delTGTTCGAG (p.Leu7Argfs) deletion Pathogenic rs587783362 GRCh38 Chromosome X, 41922962: 41922969
11 CASK NM_003688.3(CASK): c.2470C> T (p.Gln824Ter) single nucleotide variant Pathogenic rs587783364 GRCh38 Chromosome X, 41531042: 41531042
12 CASK NM_003688.3(CASK): c.430-2A> T single nucleotide variant Pathogenic rs587783366 GRCh38 Chromosome X, 41671532: 41671532
13 CASK NM_003688.3(CASK): c.708+1G> A single nucleotide variant Pathogenic rs587783368 GRCh38 Chromosome X, 41665276: 41665276
14 CASK NM_003688.3(CASK): c.764G> A (p.Arg255His) single nucleotide variant Likely pathogenic rs587783369 GRCh38 Chromosome X, 41660506: 41660506
15 CASK NM_003688.3(CASK): c.82C> T (p.Arg28Ter) single nucleotide variant Pathogenic rs587783370 GRCh38 Chromosome X, 41853205: 41853205
16 CASK NM_003688.3(CASK): c.880C> T (p.Gln294Ter) single nucleotide variant Pathogenic rs587783371 GRCh38 Chromosome X, 41636613: 41636613
17 CASK NM_003688.3(CASK): c.1976G> A (p.Gly659Asp) single nucleotide variant Pathogenic rs727505397 GRCh37 Chromosome X, 41413035: 41413035
18 CASK NM_003688.3(CASK): c.79C> T (p.Arg27Ter) single nucleotide variant Pathogenic rs794727270 GRCh37 Chromosome X, 41712461: 41712461
19 CASK NM_003688.3(CASK): c.2531_2532delAG (p.Glu844Valfs) deletion Pathogenic rs797045433 GRCh38 Chromosome X, 41524008: 41524009
20 CASK NM_003688.3(CASK): c.2377C> T (p.Gln793Ter) single nucleotide variant Pathogenic rs749742837 GRCh38 Chromosome X, 41531135: 41531135
21 CASK NM_003688.3(CASK): c.1981delC (p.Leu661Trpfs) deletion Pathogenic rs797045431 GRCh38 Chromosome X, 41553777: 41553777
22 CASK NM_003688.3(CASK): c.2303-2A> G single nucleotide variant Pathogenic rs863224854 GRCh37 Chromosome X, 41390464: 41390464
23 CASK NM_003688.3: c.116_117delCA deletion Pathogenic
24 CASK NM_003688.3(CASK): c.1837C> T (p.Arg613Ter) single nucleotide variant Pathogenic rs779508996 GRCh37 Chromosome X, 41414858: 41414858
25 CASK NM_003688.3(CASK): c.68delT (p.Phe23Serfs) deletion Pathogenic rs1135401762 GRCh37 Chromosome X, 41712472: 41712472
26 CASK NM_003688.3(CASK): c.2589+1G> T single nucleotide variant Pathogenic GRCh37 Chromosome X, 41383203: 41383203
27 CASK NM_003688.3(CASK): c.2534_2535delTT (p.Phe845Cysfs) deletion Pathogenic GRCh37 Chromosome X, 41383258: 41383259
28 CASK NM_003688.3(CASK): c.1864G> T (p.Glu622Ter) single nucleotide variant Pathogenic GRCh38 Chromosome X, 41553894: 41553894
29 CASK NM_003688.3(CASK): c.846C> G (p.Tyr282Ter) single nucleotide variant Pathogenic rs886128077 GRCh37 Chromosome X, 41495900: 41495900

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
16 ExPASy
18 FMA
27 GO
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29 HGMD
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32 ICD10
33 ICD10 via Orphanet
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42 MESH via Orphanet
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54 OMIM via Orphanet
58 PubMed
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65 SNOMED-CT via HPO
66 SNOMED-CT via Orphanet
67 TGDB
68 Tocris
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70 UMLS via Orphanet
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