PCH2E
MCID: PNT034
MIFTS: 43

Pontocerebellar Hypoplasia, Type 2e (PCH2E)

Categories: Eye diseases, Fetal diseases, Genetic diseases, Mental diseases, Metabolic diseases, Muscle diseases, Neuronal diseases, Rare diseases, Respiratory diseases

Aliases & Classifications for Pontocerebellar Hypoplasia, Type 2e

MalaCards integrated aliases for Pontocerebellar Hypoplasia, Type 2e:

Name: Pontocerebellar Hypoplasia, Type 2e 58 30 6 74
Pontocerebellar Hypoplasia Type 2 54 60 30 74
Pch2e 58 76
Progressive Microcephaly from Birth Extrapyramidal Dyskinesia Chorea Epilepsy 54
Progressive Cerebello-Cerebral Atrophy Type 2 76
Progressive Cerebello-Cerebral Atrophy 60
Hypoplasia, Pontocerebellar, Type 2e 41
Pontocerebellar Hypoplasia, Type 2d 74
Pontocerebellar Hypoplasia Type 2a 74
Pontocerebellar Hypoplasia Type 2e 12
Pontocerebellar Hypoplasia 2e 76
Pcca2 76
Pch2 60
Pcca 60

Characteristics:

Orphanet epidemiological data:

60
progressive cerebello-cerebral atrophy
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal;
pontocerebellar hypoplasia type 2
Inheritance: Autosomal recessive; Age of onset: Infancy,Neonatal; Age of death: adolescent,late childhood;

OMIM:

58
Inheritance:
autosomal recessive

Miscellaneous:
onset in infancy
progressive disorder
reported in individuals of jewish moroccan ancestry


HPO:

33
pontocerebellar hypoplasia, type 2e:
Onset and clinical course infantile onset progressive
Inheritance autosomal recessive inheritance


Classifications:



Summaries for Pontocerebellar Hypoplasia, Type 2e

NIH Rare Diseases : 54 Pontocerebellar hypoplasia type 2 (PCH2) is a rare condition that affects the development of the brain. Signs and symptoms vary but may include microcephaly, developmental delay with lack of voluntary motor development, intellectual disability and movement disorders (i.e. chorea, dystonia, and spasticity). Affected people may also experience dysphagia (difficulty swallowing), impaired vision, seizures and an inability to communicate. Children with this condition often pass away prior to age 10 years, although survival beyond age 20 years has been reported. PCH2 is caused by changes (mutations) in the TSEN54, TSEN2, TSEN34, or SEPSECS gene and is inherited in an autosomal recessive manner. Treatment is supportive and based on the signs and symptoms present in each person.

MalaCards based summary : Pontocerebellar Hypoplasia, Type 2e, also known as pontocerebellar hypoplasia type 2, is related to pontocerebellar hypoplasia and microcephaly, and has symptoms including seizures, clonus and opisthotonus. An important gene associated with Pontocerebellar Hypoplasia, Type 2e is VPS53 (VPS53 Subunit Of GARP Complex), and among its related pathways/superpathways are Gene Expression and tRNA processing. Affiliated tissues include brain, and related phenotypes are seizures and scoliosis

Disease Ontology : 12 A pontocerebellar hypoplasia that is characterized by progressive microcephaly, profound intellectual disability, spasticity and seizure, has material basis in autosomal recessive inheritance of mutation in the VPS53 gene.

OMIM : 58 Pontocerebellar hypoplasia type 2E is an autosomal recessive neurodegenerative disorder characterized by profound mental retardation, progressive microcephaly, spasticity, and early-onset epilepsy (summary by Feinstein et al., 2014). For a general phenotypic description and a discussion of genetic heterogeneity of pontocerebellar hypoplasia type 2, see PCH2A (277470). (615851)

UniProtKB/Swiss-Prot : 76 Pontocerebellar hypoplasia 2E: A neurodegenerative disorder characterized by progressive cerebello- cerebral atrophy, profound mental retardation, progressive microcephaly, spasticity, and early-onset epilepsy.

Related Diseases for Pontocerebellar Hypoplasia, Type 2e

Diseases in the Pontocerebellar Hypoplasia family:

Pontocerebellar Hypoplasia, Type 4 Pontocerebellar Hypoplasia, Type 2a
Pontocerebellar Hypoplasia, Type 1a Pontocerebellar Hypoplasia, Type 3
Pontocerebellar Hypoplasia, Type 5 Pontocerebellar Hypoplasia, Type 6
Pontocerebellar Hypoplasia, Type 2b Pontocerebellar Hypoplasia, Type 2c
Pontocerebellar Hypoplasia, Type 2d Pontocerebellar Hypoplasia, Type 1b
Pontocerebellar Hypoplasia, Type 8 Pontocerebellar Hypoplasia, Type 7
Pontocerebellar Hypoplasia, Type 10 Pontocerebellar Hypoplasia, Type 9
Pontocerebellar Hypoplasia, Type 2e Pontocerebellar Hypoplasia, Type 1c
Pontocerebellar Hypoplasia, Type 2f Pontocerebellar Hypoplasia, Type 11
Pontocerebellar Hypoplasia, Type 1d Pontocerebellar Hypoplasia, Type 12
Exosc3-Related Pontocerebellar Hypoplasia Tsen54-Related Pontocerebellar Hypoplasia
Pontocerebellar Hypoplasia Type 1

Diseases related to Pontocerebellar Hypoplasia, Type 2e via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 21)
# Related Disease Score Top Affiliating Genes
1 pontocerebellar hypoplasia 28.6 SEPSECS TSEN15 TSEN2 TSEN34 TSEN54
2 microcephaly 28.4 TSEN15 TSEN2 TSEN34 TSEN54
3 propionic acidemia 12.3
4 pontocerebellar hypoplasia, type 2d 11.4
5 methylmalonic acidemia 11.3
6 pontocerebellar hypoplasia, type 2a 11.3
7 pontocerebellar hypoplasia, type 2f 11.2
8 cleft soft palate 11.2
9 organic acidemia 11.2
10 bile duct adenocarcinoma 11.2
11 hard palate cancer 11.2
12 amino acid metabolic disorder 11.2
13 cerebral atrophy 10.4
14 3-methylglutaconic aciduria, type iii 10.1
15 encephalopathy 10.1
16 cerebral palsy 10.1
17 dyskinetic cerebral palsy 10.1
18 dystonia 10.1
19 myoclonus 10.1
20 pontocerebellar hypoplasia, type 6 9.3 TSEN2 TSEN34 TSEN54
21 pontoneocerebellar hypoplasia 9.0 SEPSECS TSEN2 TSEN34 TSEN54

Graphical network of the top 20 diseases related to Pontocerebellar Hypoplasia, Type 2e:



Diseases related to Pontocerebellar Hypoplasia, Type 2e

Symptoms & Phenotypes for Pontocerebellar Hypoplasia, Type 2e

Human phenotypes related to Pontocerebellar Hypoplasia, Type 2e:

33 (show all 15)
# Description HPO Frequency HPO Source Accession
1 seizures 33 HP:0001250
2 scoliosis 33 HP:0002650
3 global developmental delay 33 HP:0001263
4 neonatal hypotonia 33 HP:0001319
5 short stature 33 HP:0004322
6 flexion contracture 33 HP:0001371
7 osteoporosis 33 HP:0000939
8 spastic tetraplegia 33 HP:0002510
9 irritability 33 HP:0000737
10 intellectual disability, profound 33 HP:0002187
11 cerebellar atrophy 33 HP:0001272
12 hypoplasia of the corpus callosum 33 HP:0002079
13 cerebral atrophy 33 HP:0002059
14 opisthotonus 33 HP:0002179
15 progressive microcephaly 33 HP:0000253

Symptoms via clinical synopsis from OMIM:

58
Neurologic Central Nervous System:
seizures
irritability
opisthotonus
mental retardation, profound
thin corpus callosum
more
Growth Height:
short stature

Muscle Soft Tissue:
hypotonia, neonatal

Skeletal Spine:
scoliosis

Skeletal:
osteoporosis
joint contractures

Head And Neck Head:
microcephaly, progressive

Clinical features from OMIM:

615851

UMLS symptoms related to Pontocerebellar Hypoplasia, Type 2e:


seizures, clonus, opisthotonus, sleep disturbances, muscle spasticity

Drugs & Therapeutics for Pontocerebellar Hypoplasia, Type 2e

Search Clinical Trials , NIH Clinical Center for Pontocerebellar Hypoplasia, Type 2e

Genetic Tests for Pontocerebellar Hypoplasia, Type 2e

Genetic tests related to Pontocerebellar Hypoplasia, Type 2e:

# Genetic test Affiliating Genes
1 Pontocerebellar Hypoplasia Type 2 30
2 Pontocerebellar Hypoplasia, Type 2e 30 VPS53

Anatomical Context for Pontocerebellar Hypoplasia, Type 2e

MalaCards organs/tissues related to Pontocerebellar Hypoplasia, Type 2e:

42
Brain

Publications for Pontocerebellar Hypoplasia, Type 2e

Articles related to Pontocerebellar Hypoplasia, Type 2e:

(show all 16)
# Title Authors Year
1
<i>TSEN54</i> Gene-Related Pontocerebellar Hypoplasia Type 2 Could Mimic Dyskinetic Cerebral Palsy with Severe Psychomotor Retardation. ( 29410950 )
2018
2
Brain morphometry in Pontocerebellar Hypoplasia type 2. ( 27430971 )
2016
3
A combination of chorea, myoclonus, and dystonia in a patient with pontocerebellar hypoplasia type 2: a video case presentation. ( 25837317 )
2015
4
TSEN54 gene-related pontocerebellar hypoplasia type 2 presenting with exaggerated startle response: report of two cases in a family. ( 26701950 )
2015
5
Recurrent episodes of rhabdomyolysis in pontocerebellar hypoplasia type 2. ( 23177318 )
2013
6
Pontocerebellar hypoplasia type 2 and TSEN2: review of the literature and two novel mutations. ( 23562994 )
2013
7
Novel Mutations in TSEN54 in Pontocerebellar Hypoplasia Type 2. ( 23307886 )
2013
8
Molecular and neuroimaging findings in pontocerebellar hypoplasia type 2 (PCH2): is prenatal diagnosis possible? ( 20803644 )
2010
9
Rhabdomyolysis in pontocerebellar hypoplasia type 2 (PCH-2). ( 17825555 )
2008
10
Pontocerebellar hypoplasia type 2: a neuropathological update. ( 17641900 )
2007
11
Pontocerebellar hypoplasia type 2: variability in clinical and imaging findings. ( 17320436 )
2007
12
Pontocerebellar hypoplasia type 2: further clinical characterization and evidence of positive response of dyskinesia to levodopa. ( 12021950 )
2002
13
Pontocerebellar hypoplasia type 2 and Reye-like syndrome. ( 11952074 )
2002
14
Fatal outcome in a case of pontocerebellar hypoplasia type 2. ( 10978619 )
2000
15
Pontocerebellar hypoplasia type 2 (PCH2): report of two siblings. ( 10814903 )
2000
16
The syndrome of autosomal recessive pontocerebellar hypoplasia, microcephaly, and extrapyramidal dyskinesia (pontocerebellar hypoplasia type 2): compiled data from 10 pedigrees. ( 7854532 )
1995

Variations for Pontocerebellar Hypoplasia, Type 2e

UniProtKB/Swiss-Prot genetic disease variations for Pontocerebellar Hypoplasia, Type 2e:

76
# Symbol AA change Variation ID SNP ID
1 VPS53 p.Gln695Arg VAR_071803 rs587777465

ClinVar genetic disease variations for Pontocerebellar Hypoplasia, Type 2e:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 VPS53 NM_001128159.2(VPS53): c.2084A> G (p.Gln695Arg) single nucleotide variant Pathogenic rs587777465 GRCh37 Chromosome 17, 436083: 436083
2 VPS53 NM_001128159.2(VPS53): c.2084A> G (p.Gln695Arg) single nucleotide variant Pathogenic rs587777465 GRCh38 Chromosome 17, 532843: 532843
3 VPS53 NM_001128159.2(VPS53): c.1556+5G> A single nucleotide variant Pathogenic rs587777466 GRCh37 Chromosome 17, 465738: 465738
4 VPS53 NM_001128159.2(VPS53): c.1556+5G> A single nucleotide variant Pathogenic rs587777466 GRCh38 Chromosome 17, 562498: 562498
5 VPS53 NM_001128159.2(VPS53): c.2347C> T (p.Gln783Ter) single nucleotide variant Uncertain significance rs1434668575 GRCh37 Chromosome 17, 422520: 422520
6 VPS53 NM_001128159.2(VPS53): c.2347C> T (p.Gln783Ter) single nucleotide variant Uncertain significance rs1434668575 GRCh38 Chromosome 17, 519280: 519280
7 VPS53 NM_001128159.2(VPS53): c.1312_1313+2delAAGT deletion Likely pathogenic rs768997239 GRCh37 Chromosome 17, 489507: 489511
8 VPS53 NM_001128159.2(VPS53): c.1312_1313+2delAAGT deletion Likely pathogenic rs768997239 GRCh38 Chromosome 17, 586268: 586271
9 VPS53 NM_001128159.2(VPS53): c.1516C> T (p.Arg506Ter) single nucleotide variant Likely pathogenic rs200594402 GRCh37 Chromosome 17, 465783: 465783
10 VPS53 NM_001128159.2(VPS53): c.1516C> T (p.Arg506Ter) single nucleotide variant Likely pathogenic rs200594402 GRCh38 Chromosome 17, 562543: 562543

Expression for Pontocerebellar Hypoplasia, Type 2e

Search GEO for disease gene expression data for Pontocerebellar Hypoplasia, Type 2e.

Pathways for Pontocerebellar Hypoplasia, Type 2e

GO Terms for Pontocerebellar Hypoplasia, Type 2e

Cellular components related to Pontocerebellar Hypoplasia, Type 2e according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleolus GO:0005730 9.26 TSEN15 TSEN2 TSEN34 TSEN54
2 tRNA-intron endonuclease complex GO:0000214 8.8 TSEN2 TSEN34 TSEN54

Biological processes related to Pontocerebellar Hypoplasia, Type 2e according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mRNA processing GO:0006397 9.67 TSEN15 TSEN2 TSEN34 TSEN54
2 nucleic acid phosphodiester bond hydrolysis GO:0090305 9.58 TSEN15 TSEN2 TSEN34
3 tRNA processing GO:0008033 9.56 TSEN15 TSEN2 TSEN34 TSEN54
4 RNA phosphodiester bond hydrolysis GO:0090501 9.5 TSEN15 TSEN2 TSEN34
5 RNA phosphodiester bond hydrolysis, endonucleolytic GO:0090502 9.46 TSEN15 TSEN2 TSEN34 TSEN54
6 tRNA-type intron splice site recognition and cleavage GO:0000379 9.13 TSEN2 TSEN34 TSEN54
7 tRNA splicing, via endonucleolytic cleavage and ligation GO:0006388 8.92 TSEN15 TSEN2 TSEN34 TSEN54

Molecular functions related to Pontocerebellar Hypoplasia, Type 2e according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 lyase activity GO:0016829 9.26 TSEN2 TSEN34
2 endonuclease activity GO:0004519 9.16 TSEN2 TSEN34
3 nuclease activity GO:0004518 9.13 TSEN15 TSEN2 TSEN34
4 tRNA-intron endonuclease activity GO:0000213 8.92 TSEN15 TSEN2 TSEN34 TSEN54

Sources for Pontocerebellar Hypoplasia, Type 2e

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
20 FMA
29 GO
30 GTR
31 HGMD
32 HMDB
33 HPO
34 ICD10
35 ICD10 via Orphanet
36 ICD9CM
37 IUPHAR
38 KEGG
39 LifeMap
41 LOVD
43 MedGen
45 MeSH
46 MESH via Orphanet
47 MGI
50 NCI
51 NCIt
52 NDF-RT
55 NINDS
56 Novoseek
58 OMIM
59 OMIM via Orphanet
63 PubMed
65 QIAGEN
70 SNOMED-CT via HPO
71 SNOMED-CT via Orphanet
72 TGDB
73 Tocris
74 UMLS
75 UMLS via Orphanet
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