PCH4
MCID: PNT043
MIFTS: 40

Pontocerebellar Hypoplasia, Type 4 (PCH4)

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 4

MalaCards integrated aliases for Pontocerebellar Hypoplasia, Type 4:

Name: Pontocerebellar Hypoplasia, Type 4 56
Pontocerebellar Hypoplasia Type 4 56 12 52 58 29 13 6 15 71
Olivopontocerebellar Hypoplasia 58 29 6
Pch4 56 58 73
Encephalopathy Fatal Infantile with Olivopontocerebellar Hypoplasia 52 73
Encephalopathy, Fatal Infantile, with Olivopontocerebellar Hypoplasia 56
Fatal Infantile Encephalopathy with Olivopontocerebellar Hypoplasia 58
Hypoplasia, Pontocerebellar, Type 4 39
Young Mckeever Squier Syndrome 43
Pontocerebellar Hypoplasia 4 73

Characteristics:

Orphanet epidemiological data:

58
pontocerebellar hypoplasia type 4
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal; Age of death: early childhood,infantile;

OMIM:

56
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth
death usually in infancy


HPO:

31
pontocerebellar hypoplasia, type 4:
Clinical modifier death in infancy
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:

Orphanet: 58  
Rare neurological diseases
Developmental anomalies during embryogenesis


External Ids:

Disease Ontology 12 DOID:0060273
OMIM 56 225753
OMIM Phenotypic Series 56 PS607596
MESH via Orphanet 44 C536716
ICD10 via Orphanet 33 Q04.3
UMLS via Orphanet 72 C1856974
Orphanet 58 ORPHA166063
MedGen 41 C1856974
UMLS 71 C1856974

Summaries for Pontocerebellar Hypoplasia, Type 4

NIH Rare Diseases : 52 The following summary is from Orphanet , a European reference portal for information on rare diseases and orphan drugs. Orpha Number: 166063 Definition Pontocerebellar hypoplasia type 4 (PCH4) is a very rare form of PCH (see this term), characterized by prenatal onset of polyhydramnios and contractures followed by hypertonia, severe clonus, primary hypoventilation leading to an early postnatal death. Epidemiology PCH4 has been reported in 10 families to date. Clinical description PCH4 is characterized prenatally by polyhydramnios. Neonates present with microcephaly , central apnea requiring respiratory support, dysmorphism (sloping forehead, midface hypoplasia, micrognathia ), contractures (50%) ''arthrogryposis'', severe clonus,and hypertonia. PCH4 affected babies usually do not live beyond the neonatal period. Weaning from mechanical ventilation is difficult and usually fails. Etiology PCH4 is caused by a compound heterozygosity for p.A307S plus non-sense or splice site mutations in the TSEN54 gene . There is significant overlap both in phenotype and in genotype between pontocerebellar hypoplasia types 4 and 5 (see this term). PCH4 is inherited in an autosomal recessive manner. Diagnostic methods MRI (usually performed at autopsy) demonstrates microcephaly due to delayed neocortical maturation with underdeveloped cerebral hemispheres, increased volume of extracerebral cerebrospinal fluid, wide midline cava, pontocerebellar hypoplasia with large denuded areas without folia of the cerebellar hemispheric cortex and a severely affected vermis. Visit the Orphanet disease page for more resources.

MalaCards based summary : Pontocerebellar Hypoplasia, Type 4, also known as pontocerebellar hypoplasia type 4, is related to pontocerebellar hypoplasia, type 5 and polyhydramnios, and has symptoms including seizures, myoclonus and muscle spasticity. An important gene associated with Pontocerebellar Hypoplasia, Type 4 is TSEN54 (TRNA Splicing Endonuclease Subunit 54). Affiliated tissues include cerebellum, cortex and brain, and related phenotypes are seizures and abnormal facial shape

Disease Ontology : 12 A pontocerebellar hypoplasia that is characterized by progressive microcephaly, hypertonia, myoclonus, seizure and early lethality, has material basis in autosomal recessive inheritance of mutation in the TSEN54 gene.

OMIM : 56 Pontocerebellar hypoplasia (PCH) represents a heterogeneous group of disorders characterized by an abnormally small cerebellum and brainstem. Pontocerebellar hypoplasia type 4 (PCH4) is characterized by severe course and early lethality (Budde et al., 2008). For a phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (607596). (225753)

UniProtKB/Swiss-Prot : 73 Pontocerebellar hypoplasia 4: A disorder characterized by an abnormally small cerebellum and brainstem, severe neonatal encephalopathy, microcephaly, myoclonus and muscular hypertonia. There is a severe inferior olivary and pontine neuronal loss and a diffuse white matter gliosis.

Related Diseases for Pontocerebellar Hypoplasia, Type 4

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
Pontocerebellar Hypoplasia, Type 13 Exosc3-Related Pontocerebellar Hypoplasia
Tsen54-Related Pontocerebellar Hypoplasia Pontocerebellar Hypoplasia Type 1

Diseases related to Pontocerebellar Hypoplasia, Type 4 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 35)
# Related Disease Score Top Affiliating Genes
1 pontocerebellar hypoplasia, type 5 32.2 TSEN54 TRIP13
2 polyhydramnios 29.8 TSEN54 TRIP13
3 spinal muscular atrophy, type i 29.7 TRIP13 ATAD3C
4 microcephaly 28.9 TSEN54 TSEN15 TRIP13 TBC1D23
5 pontocerebellar hypoplasia 28.1 TSEN54 TSEN15 TRIP13 TBC1D23 LOC112533671
6 pontocerebellar hypoplasia, type 6 11.3
7 encephalopathy 10.4
8 myoclonus 10.4
9 polymicrogyria with or without vascular-type ehlers-danlos syndrome 10.2
10 polymicrogyria 10.2
11 tsen54-related pontocerebellar hypoplasia 10.2
12 glioblastoma multiforme 10.2
13 malignant glioma 10.2
14 glioma 10.2
15 glial tumor 10.2
16 spinal muscular atrophy 10.2
17 muscular atrophy 10.2
18 hypertonia 10.1
19 pontocerebellar hypoplasia, type 2d 10.0 TSEN54 TRIP13
20 spinal muscular atrophy, x-linked 2 10.0
21 pontocerebellar hypoplasia, type 1b 10.0
22 autosomal recessive disease 10.0
23 respiratory failure 10.0
24 progressive muscular atrophy 10.0
25 anterior horn cell disease 10.0
26 cerebral atrophy 10.0
27 hypotonia 10.0
28 pontocerebellar hypoplasia, type 2a 10.0 TSEN54 TRIP13
29 mental retardation and microcephaly with pontine and cerebellar hypoplasia 10.0 TSEN54 TRIP13
30 spastic paraplegia 63, autosomal recessive 9.8 TBC1D23 ATAD3C
31 phosphoserine aminotransferase deficiency 9.8 TSEN54 TSEN15
32 pontocerebellar hypoplasia, type 2e 9.7 TSEN54 TSEN15
33 congenital disorder of glycosylation, type in 9.6 TSEN54 TRIP13
34 hemoglobin h disease 9.6 TSEN54 TSEN15
35 pontocerebellar hypoplasia, type 3 8.5 TSEN15 TRIP13 TBC1D23 ATAD3C ATAD3B

Graphical network of the top 20 diseases related to Pontocerebellar Hypoplasia, Type 4:



Diseases related to Pontocerebellar Hypoplasia, Type 4

Symptoms & Phenotypes for Pontocerebellar Hypoplasia, Type 4

Human phenotypes related to Pontocerebellar Hypoplasia, Type 4:

58 31 (show all 25)
# Description HPO Frequency Orphanet Frequency HPO Source Accession
1 seizures 58 31 frequent (33%) Frequent (79-30%) HP:0001250
2 abnormal facial shape 58 31 frequent (33%) Frequent (79-30%) HP:0001999
3 hypertonia 58 31 frequent (33%) Frequent (79-30%) HP:0001276
4 myoclonus 58 31 frequent (33%) Frequent (79-30%) HP:0001336
5 polyhydramnios 58 31 frequent (33%) Frequent (79-30%) HP:0001561
6 hypoplasia of the brainstem 58 31 frequent (33%) Frequent (79-30%) HP:0002365
7 arthrogryposis multiplex congenita 58 31 frequent (33%) Frequent (79-30%) HP:0002804
8 central apnea 58 31 frequent (33%) Frequent (79-30%) HP:0002871
9 respiratory failure requiring assisted ventilation 58 31 frequent (33%) Frequent (79-30%) HP:0004887
10 olivopontocerebellar hypoplasia 58 31 frequent (33%) Frequent (79-30%) HP:0006955
11 congenital microcephaly 58 31 frequent (33%) Frequent (79-30%) HP:0011451
12 micrognathia 58 31 occasional (7.5%) Occasional (29-5%) HP:0000347
13 sloping forehead 58 31 occasional (7.5%) Occasional (29-5%) HP:0000340
14 midface retrusion 58 31 occasional (7.5%) Occasional (29-5%) HP:0011800
15 spasticity 31 HP:0001257
16 microcephaly 31 HP:0000252
17 abnormality of metabolism/homeostasis 31 HP:0001939
18 severe global developmental delay 31 HP:0011344
19 cerebellar hypoplasia 31 HP:0001321
20 hypoplasia of the pons 31 HP:0012110
21 respiratory failure 31 HP:0002878
22 congenital contracture 31 HP:0002803
23 gliosis 31 HP:0002171
24 infantile encephalopathy 31 HP:0007105
25 loss of purkinje cells in the cerebellar vermis 31 HP:0007001

Symptoms via clinical synopsis from OMIM:

56
Neurologic Central Nervous System:
seizures
spasticity
myoclonus
cerebellar hypoplasia
delayed psychomotor development, profound
more
Prenatal Manifestations Amniotic Fluid:
polyhydramnios

Abdomen Gastrointestinal:
swallowing disturbances

Muscle Soft Tissue:
hypertonia at birth

Head And Neck Head:
microcephaly

Respiratory:
little spontaneous breath
central respiratory failure

Skeletal:
congenital contractures

Clinical features from OMIM:

225753

UMLS symptoms related to Pontocerebellar Hypoplasia, Type 4:


seizures, myoclonus, muscle spasticity

Drugs & Therapeutics for Pontocerebellar Hypoplasia, Type 4

Search Clinical Trials , NIH Clinical Center for Pontocerebellar Hypoplasia, Type 4

Cochrane evidence based reviews: young mckeever squier syndrome

Genetic Tests for Pontocerebellar Hypoplasia, Type 4

Genetic tests related to Pontocerebellar Hypoplasia, Type 4:

# Genetic test Affiliating Genes
1 Pontocerebellar Hypoplasia Type 4 29 TSEN54
2 Olivopontocerebellar Hypoplasia 29

Anatomical Context for Pontocerebellar Hypoplasia, Type 4

MalaCards organs/tissues related to Pontocerebellar Hypoplasia, Type 4:

40
Cerebellum, Cortex, Brain, Pons, Eye

Publications for Pontocerebellar Hypoplasia, Type 4

Articles related to Pontocerebellar Hypoplasia, Type 4:

# Title Authors PMID Year
1
Pontocerebellar hypoplasia: clinical, pathologic, and genetic studies. 56 6
20956791 2010
2
tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia. 56 6
18711368 2008
3
TSEN54 mutations cause pontocerebellar hypoplasia type 5. 6
21368912 2011
4
Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia. 56
20952379 2011
5
TSEN54-Related Pontocerebellar Hypoplasia 6
20301773 2009
6
Pontocerebellar hypoplasia type 2: a neuropathological update. 6
17641900 2007
7
Severe, fetal-onset form of olivopontocerebellar hypoplasia in three sibs: PCH type 5? 56
16470708 2006
8
Fatal infantile encephalopathy with olivopontocerebellar hypoplasia and micrencephaly. Report of three siblings. 56
8480512 1993
9
Novel TSEN54 mutation causing pontocerebellar hypoplasia type 4. 61
21824568 2011

Variations for Pontocerebellar Hypoplasia, Type 4

ClinVar genetic disease variations for Pontocerebellar Hypoplasia, Type 4:

6 (show all 19) ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎ ‎‎
# Gene Name Type Significance ClinVarId dbSNP ID GRCh37 Pos GRCh38 Pos
1 TSEN54 NM_207346.3(TSEN54):c.1A>C (p.Met1Leu)SNV Pathogenic 160132 rs587784478 17:73512642-73512642 17:75516561-75516561
2 TSEN54 NM_207346.3(TSEN54):c.575_576del (p.His192fs)deletion Pathogenic 160136 rs587784479 17:73517542-73517543 17:75521461-75521462
3 TSEN54 NM_207346.3(TSEN54):c.1335del (p.Leu446fs)deletion Pathogenic 160129 rs587784476 17:73519765-73519765 17:75523684-75523684
4 TSEN54 NM_207346.3(TSEN54):c.1138G>T (p.Glu380Ter)SNV Pathogenic 160125 rs587784475 17:73518300-73518300 17:75522219-75522219
5 TSEN54 NM_207346.3(TSEN54):c.736C>T (p.Gln246Ter)SNV Pathogenic 2122 rs113994153 17:73517898-73517898 17:75521817-75521817
6 TSEN54 NM_207346.3(TSEN54):c.1027C>T (p.Gln343Ter)SNV Pathogenic 2123 rs113994154 17:73518189-73518189 17:75522108-75522108
7 TSEN54 NM_207346.3(TSEN54):c.1172_1185del (p.Gln391fs)deletion Pathogenic 30751 rs886037629 17:73518332-73518345 17:75522251-75522264
8 TSEN54 NM_207346.3(TSEN54):c.940del (p.Leu314fs)deletion Pathogenic 561138 rs1012275384 17:73518100-73518100 17:75522019-75522019
9 TSEN54 NM_207346.3(TSEN54):c.919G>T (p.Ala307Ser)SNV Pathogenic/Likely pathogenic 2120 rs113994152 17:73518081-73518081 17:75522000-75522000
10 TSEN54 NM_207346.3(TSEN54):c.1511T>C (p.Leu504Pro)SNV Likely pathogenic 160131 rs587784477 17:73520423-73520423 17:75524342-75524342
11 TSEN54 NM_207346.3(TSEN54):c.3_8dup (p.2_3EP[4])duplication Conflicting interpretations of pathogenicity 96674 rs398124622 17:73512643-73512644 17:75516562-75516563
12 TSEN54 NM_207346.3(TSEN54):c.622C>T (p.Arg208Trp)SNV Uncertain significance 198637 rs147165460 17:73517590-73517590 17:75521509-75521509
13 TSEN54 NM_207346.3(TSEN54):c.83C>T (p.Ser28Leu)SNV Uncertain significance 212455 rs201089582 17:73512853-73512853 17:75516772-75516772
14 TSEN54 NM_207346.3(TSEN54):c.964C>G (p.Leu322Val)SNV Uncertain significance 160140 rs587784480 17:73518126-73518126 17:75522045-75522045
15 TSEN54 NM_207346.3(TSEN54):c.1114G>A (p.Val372Met)SNV Uncertain significance 160124 rs200434678 17:73518276-73518276 17:75522195-75522195
16 TSEN54 NM_207346.3(TSEN54):c.1181A>G (p.Gln394Arg)SNV Uncertain significance 160126 rs560589823 17:73518343-73518343 17:75522262-75522262
17 TSEN54 NM_207346.3(TSEN54):c.277T>C (p.Ser93Pro)SNV Uncertain significance 38455 rs113994151 17:73513145-73513145 17:75517064-75517064
18 TSEN54 NM_207346.3(TSEN54):c.114T>G (p.His38Gln)SNV Benign 96671 rs8079373 17:73512884-73512884 17:75516803-75516803
19 TSEN54 NM_207346.3(TSEN54):c.1041G>C (p.Lys347Asn)SNV Benign 160123 rs9911502 17:73518203-73518203 17:75522122-75522122

UniProtKB/Swiss-Prot genetic disease variations for Pontocerebellar Hypoplasia, Type 4:

73
# Symbol AA change Variation ID SNP ID
1 TSEN54 p.Ser93Pro VAR_054812 rs113994151
2 TSEN54 p.Ala307Ser VAR_054813 rs113994152

Expression for Pontocerebellar Hypoplasia, Type 4

Search GEO for disease gene expression data for Pontocerebellar Hypoplasia, Type 4.

Pathways for Pontocerebellar Hypoplasia, Type 4

GO Terms for Pontocerebellar Hypoplasia, Type 4

Biological processes related to Pontocerebellar Hypoplasia, Type 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion organization GO:0007005 9.32 ATAD3C ATAD3B
2 tRNA processing GO:0008033 9.26 TSEN54 TSEN15
3 RNA phosphodiester bond hydrolysis, endonucleolytic GO:0090502 9.16 TSEN54 TSEN15
4 RNA phosphodiester bond hydrolysis GO:0090501 8.96 TSEN54 TSEN15
5 tRNA splicing, via endonucleolytic cleavage and ligation GO:0006388 8.62 TSEN54 TSEN15

Molecular functions related to Pontocerebellar Hypoplasia, Type 4 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 tRNA-intron endonuclease activity GO:0000213 8.62 TSEN54 TSEN15

Sources for Pontocerebellar Hypoplasia, Type 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
19 FMA
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
43 MeSH
44 MESH via Orphanet
45 MGI
48 NCI
49 NCIt
50 NDF-RT
53 NINDS
54 Novoseek
56 OMIM
57 OMIM via Orphanet
61 PubMed
63 QIAGEN
68 SNOMED-CT via HPO
69 TGDB
70 Tocris
71 UMLS
72 UMLS via Orphanet
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