PCH4
MCID: PNT043
MIFTS: 35

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 57
Pontocerebellar Hypoplasia Type 4 57 12 53 59 29 13 6 15 72
Olivopontocerebellar Hypoplasia 59 29 6
Pch4 57 59 74
Encephalopathy Fatal Infantile with Olivopontocerebellar Hypoplasia 53 74
Encephalopathy, Fatal Infantile, with Olivopontocerebellar Hypoplasia 57
Fatal Infantile Encephalopathy with Olivopontocerebellar Hypoplasia 59
Hypoplasia, Pontocerebellar, Type 4 40
Young Mckeever Squier Syndrome 44
Pontocerebellar Hypoplasia 4 74

Characteristics:

Orphanet epidemiological data:

59
pontocerebellar hypoplasia type 4
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Antenatal,Neonatal; Age of death: early childhood,infantile;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
onset at birth
death usually in infancy


HPO:

32
pontocerebellar hypoplasia, type 4:
Clinical modifier death in infancy
Inheritance autosomal recessive inheritance
Onset and clinical course congenital onset


Classifications:



External Ids:

Disease Ontology 12 DOID:0060273
MESH via Orphanet 45 C536716
ICD10 via Orphanet 34 Q04.3
UMLS via Orphanet 73 C1856974
Orphanet 59 ORPHA166063
MedGen 42 C1856974
UMLS 72 C1856974

Summaries for Pontocerebellar Hypoplasia, Type 4

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 166063DefinitionPontocerebellar 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.EpidemiologyPCH4 has been reported in 10 families to date.Clinical descriptionPCH4 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.EtiologyPCH4 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 methodsMRI (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 pontocerebellar hypoplasia, type 6, 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 spasticity

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 : 57 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 : 74 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 1

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

(show all 30)
# Related Disease Score Top Affiliating Genes
1 pontocerebellar hypoplasia, type 5 11.4
2 pontocerebellar hypoplasia, type 6 11.3
3 microcephaly 10.4
4 encephalopathy 10.4
5 myoclonus 10.4
6 polymicrogyria with or without vascular-type ehlers-danlos syndrome 10.2
7 polymicrogyria 10.2
8 tsen54-related pontocerebellar hypoplasia 10.2
9 microencephaly 10.2
10 glioblastoma multiforme 10.2
11 malignant glioma 10.2
12 glioblastoma 10.2
13 glioma 10.2
14 glial tumor 10.2
15 spinal muscular atrophy 10.2
16 muscular atrophy 10.2
17 pontocerebellar hypoplasia 10.1
18 polyhydramnios 10.1
19 hypertonia 10.1
20 spinal muscular atrophy, type i 10.0
21 spinal muscular atrophy, x-linked 2 10.0
22 pontocerebellar hypoplasia, type 1b 10.0
23 autosomal recessive disease 10.0
24 respiratory failure 10.0
25 progressive muscular atrophy 10.0
26 anterior horn cell disease 10.0
27 cerebral atrophy 10.0
28 hypotonia 10.0
29 pontocerebellar hypoplasia, type 2a 9.4 TSEN54 CASKIN2
30 pontoneocerebellar hypoplasia 9.2 TSEN54 CASKIN2

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:

32 (show all 15)
# Description HPO Frequency HPO Source Accession
1 seizures 32 HP:0001250
2 spasticity 32 HP:0001257
3 microcephaly 32 HP:0000252
4 abnormality of metabolism/homeostasis 32 HP:0001939
5 severe global developmental delay 32 HP:0011344
6 myoclonus 32 HP:0001336
7 cerebellar hypoplasia 32 HP:0001321
8 polyhydramnios 32 HP:0001561
9 respiratory failure 32 HP:0002878
10 gliosis 32 HP:0002171
11 congenital contracture 32 HP:0002803
12 hypoplasia of the pons 32 HP:0012110
13 infantile encephalopathy 32 HP:0007105
14 loss of purkinje cells in the cerebellar vermis 32 HP:0007001
15 hypoplasia of the brainstem 32 HP:0002365

Symptoms via clinical synopsis from OMIM:

57
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:

41
Cerebellum, Cortex, Brain, Pons

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. 8 71
20956791 2010
2
tRNA splicing endonuclease mutations cause pontocerebellar hypoplasia. 8 71
18711368 2008
3
TSEN54 mutations cause pontocerebellar hypoplasia type 5. 71
21368912 2011
4
Clinical, neuroradiological and genetic findings in pontocerebellar hypoplasia. 8
20952379 2011
5
TSEN54-Related Pontocerebellar Hypoplasia 71
20301773 2009
6
Pontocerebellar hypoplasia type 2: a neuropathological update. 71
17641900 2007
7
Severe, fetal-onset form of olivopontocerebellar hypoplasia in three sibs: PCH type 5? 8
16470708 2006
8
Fatal infantile encephalopathy with olivopontocerebellar hypoplasia and micrencephaly. Report of three siblings. 8
8480512 1993
9
Novel TSEN54 mutation causing pontocerebellar hypoplasia type 4. 38
21824568 2011

Variations for Pontocerebellar Hypoplasia, Type 4

ClinVar genetic disease variations for Pontocerebellar Hypoplasia, Type 4:

6 (show all 16)
# Gene Variation Type Significance SNP ID GRCh37 Pos GRCh38 Pos
1 TSEN54 NM_207346.3(TSEN54): c.277T> C (p.Ser93Pro) single nucleotide variant Pathogenic rs113994151 17:73513145-73513145 17:75517064-75517064
2 TSEN54 NM_207346.3(TSEN54): c.1172_1185del (p.Gln391fs) deletion Pathogenic rs886037629 17:73518334-73518347 17:75522253-75522266
3 TSEN54 NM_207346.3(TSEN54): c.940del (p.Leu314fs) deletion Pathogenic 17:73518100-73518100 17:75522019-75522019
4 TSEN54 NM_207346.3(TSEN54): c.1027C> T (p.Gln343Ter) single nucleotide variant Pathogenic rs113994154 17:73518189-73518189 17:75522108-75522108
5 TSEN54 NM_207346.3(TSEN54): c.736C> T (p.Gln246Ter) single nucleotide variant Pathogenic rs113994153 17:73517898-73517898 17:75521817-75521817
6 TSEN54 NM_207346.3(TSEN54): c.1335del (p.Leu446fs) deletion Pathogenic rs587784476 17:73519765-73519765 17:75523684-75523684
7 TSEN54 NM_207346.3(TSEN54): c.1138G> T (p.Glu380Ter) single nucleotide variant Pathogenic rs587784475 17:73518300-73518300 17:75522219-75522219
8 TSEN54 NM_207346.3(TSEN54): c.575_576del (p.His192fs) deletion Pathogenic rs587784479 17:73517543-73517544 17:75521462-75521463
9 TSEN54 NM_207346.3(TSEN54): c.1A> C (p.Met1Leu) single nucleotide variant Pathogenic rs587784478 17:73512642-73512642 17:75516561-75516561
10 TSEN54 NM_207346.3(TSEN54): c.919G> T (p.Ala307Ser) single nucleotide variant Pathogenic/Likely pathogenic rs113994152 17:73518081-73518081 17:75522000-75522000
11 TSEN54 NM_207346.3(TSEN54): c.1511T> C (p.Leu504Pro) single nucleotide variant Likely pathogenic rs587784477 17:73520423-73520423 17:75524342-75524342
12 TSEN54 NM_207346.3(TSEN54): c.622C> T (p.Arg208Trp) single nucleotide variant Uncertain significance rs147165460 17:73517590-73517590 17:75521509-75521509
13 TSEN54 NM_207346.3(TSEN54): c.83C> T (p.Ser28Leu) single nucleotide variant Uncertain significance rs201089582 17:73512853-73512853 17:75516772-75516772
14 TSEN54 NM_207346.3(TSEN54): c.1114G> A (p.Val372Met) single nucleotide variant Uncertain significance rs200434678 17:73518276-73518276 17:75522195-75522195
15 TSEN54 NM_207346.3(TSEN54): c.964C> G (p.Leu322Val) single nucleotide variant Uncertain significance rs587784480 17:73518126-73518126 17:75522045-75522045
16 TSEN54 NM_207346.3(TSEN54): c.1181A> G (p.Gln394Arg) single nucleotide variant Uncertain significance rs560589823 17:73518343-73518343 17:75522262-75522262

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

74
# 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

Sources for Pontocerebellar Hypoplasia, Type 4

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
17 EFO
18 ExPASy
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28 GO
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30 HGMD
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33 ICD10
34 ICD10 via Orphanet
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57 OMIM
58 OMIM via Orphanet
62 PubMed
64 QIAGEN
69 SNOMED-CT via HPO
70 TGDB
71 Tocris
72 UMLS
73 UMLS via Orphanet
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