MCID: PNT043
MIFTS: 30

Pontocerebellar Hypoplasia, Type 4

Categories: Genetic diseases, Rare diseases, Neuronal diseases, Fetal diseases, Muscle diseases, Eye diseases, Metabolic 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 73
Olivopontocerebellar Hypoplasia 59 29 6
Pch4 57 59 75
Encephalopathy Fatal Infantile with Olivopontocerebellar Hypoplasia 53 75
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 75

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:
Mortality/Aging death in infancy
Onset and clinical course congenital onset
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 225753
Disease Ontology 12 DOID:0060273
Orphanet 59 ORPHA166063
MESH via Orphanet 45 C536716
UMLS via Orphanet 74 C1856974
ICD10 via Orphanet 34 Q04.3
MedGen 42 C1856974
UMLS 73 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: 166063Disease definitionPontocerebellar 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 microcephaly, and has symptoms including muscle spasticity, myoclonus and seizures. 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

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 : 75 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

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

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

Human phenotypes related to Pontocerebellar Hypoplasia, Type 4:

32 (show all 14)
# 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 gliosis 32 HP:0002171
10 congenital contracture 32 HP:0002803
11 hypoplasia of the pons 32 HP:0012110
12 loss of purkinje cells in the cerebellar vermis 32 HP:0007001
13 hypoplasia of the brainstem 32 HP:0002365
14 infantile encephalopathy 32 HP:0007105

UMLS symptoms related to Pontocerebellar Hypoplasia, Type 4:


muscle spasticity, myoclonus, seizures

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 Year
1
Novel TSEN54 mutation causing pontocerebellar hypoplasia type 4. ( 21824568 )
2011

Variations for Pontocerebellar Hypoplasia, Type 4

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

75
# Symbol AA change Variation ID SNP ID
1 TSEN54 p.Ser93Pro VAR_054812 rs113994151
2 TSEN54 p.Ala307Ser VAR_054813 rs113994152

ClinVar genetic disease variations for Pontocerebellar Hypoplasia, Type 4:

6
(show all 26)
# Gene Variation Type Significance SNP ID Assembly Location
1 TSEN54 NM_207346.2(TSEN54): c.919G> T (p.Ala307Ser) single nucleotide variant Pathogenic/Likely pathogenic rs113994152 GRCh37 Chromosome 17, 73518081: 73518081
2 TSEN54 NM_207346.2(TSEN54): c.919G> T (p.Ala307Ser) single nucleotide variant Pathogenic/Likely pathogenic rs113994152 GRCh38 Chromosome 17, 75522000: 75522000
3 TSEN54 NM_207346.2(TSEN54): c.736C> T (p.Gln246Ter) single nucleotide variant Pathogenic rs113994153 GRCh37 Chromosome 17, 73517898: 73517898
4 TSEN54 NM_207346.2(TSEN54): c.736C> T (p.Gln246Ter) single nucleotide variant Pathogenic rs113994153 GRCh38 Chromosome 17, 75521817: 75521817
5 TSEN54 NM_207346.2(TSEN54): c.1027C> T (p.Gln343Ter) single nucleotide variant Pathogenic rs113994154 GRCh37 Chromosome 17, 73518189: 73518189
6 TSEN54 NM_207346.2(TSEN54): c.1027C> T (p.Gln343Ter) single nucleotide variant Pathogenic rs113994154 GRCh38 Chromosome 17, 75522108: 75522108
7 TSEN54 NM_207346.2(TSEN54): c.277T> C (p.Ser93Pro) single nucleotide variant Pathogenic rs113994151 GRCh37 Chromosome 17, 73513145: 73513145
8 TSEN54 NM_207346.2(TSEN54): c.277T> C (p.Ser93Pro) single nucleotide variant Pathogenic rs113994151 GRCh38 Chromosome 17, 75517064: 75517064
9 TSEN54 NM_207346.2(TSEN54): c.1172_1185delAGAGGAGCCAGCGC (p.Gln391Profs) deletion Pathogenic rs886037629 GRCh38 Chromosome 17, 75522253: 75522266
10 TSEN54 NM_207346.2(TSEN54): c.1172_1185delAGAGGAGCCAGCGC (p.Gln391Profs) deletion Pathogenic rs886037629 GRCh37 Chromosome 17, 73518334: 73518347
11 TSEN54 NM_207346.2(TSEN54): c.1A> C (p.Met1Leu) single nucleotide variant Pathogenic rs587784478 GRCh37 Chromosome 17, 73512642: 73512642
12 TSEN54 NM_207346.2(TSEN54): c.1A> C (p.Met1Leu) single nucleotide variant Pathogenic rs587784478 GRCh38 Chromosome 17, 75516561: 75516561
13 TSEN54 NM_207346.2(TSEN54): c.575_576delAC (p.His192Leufs) deletion Pathogenic rs587784479 GRCh37 Chromosome 17, 73517543: 73517544
14 TSEN54 NM_207346.2(TSEN54): c.575_576delAC (p.His192Leufs) deletion Pathogenic rs587784479 GRCh38 Chromosome 17, 75521462: 75521463
15 TSEN54 NM_207346.2(TSEN54): c.964C> G (p.Leu322Val) single nucleotide variant Uncertain significance rs587784480 GRCh37 Chromosome 17, 73518126: 73518126
16 TSEN54 NM_207346.2(TSEN54): c.964C> G (p.Leu322Val) single nucleotide variant Uncertain significance rs587784480 GRCh38 Chromosome 17, 75522045: 75522045
17 TSEN54 NM_207346.2(TSEN54): c.1114G> A (p.Val372Met) single nucleotide variant Uncertain significance rs200434678 GRCh37 Chromosome 17, 73518276: 73518276
18 TSEN54 NM_207346.2(TSEN54): c.1114G> A (p.Val372Met) single nucleotide variant Uncertain significance rs200434678 GRCh38 Chromosome 17, 75522195: 75522195
19 TSEN54 NM_207346.2(TSEN54): c.1138G> T (p.Glu380Ter) single nucleotide variant Pathogenic rs587784475 GRCh37 Chromosome 17, 73518300: 73518300
20 TSEN54 NM_207346.2(TSEN54): c.1138G> T (p.Glu380Ter) single nucleotide variant Pathogenic rs587784475 GRCh38 Chromosome 17, 75522219: 75522219
21 TSEN54 NM_207346.2(TSEN54): c.1181A> G (p.Gln394Arg) single nucleotide variant Uncertain significance rs560589823 GRCh37 Chromosome 17, 73518343: 73518343
22 TSEN54 NM_207346.2(TSEN54): c.1181A> G (p.Gln394Arg) single nucleotide variant Uncertain significance rs560589823 GRCh38 Chromosome 17, 75522262: 75522262
23 TSEN54 NM_207346.2(TSEN54): c.1335delC (p.Leu446Trpfs) deletion Pathogenic rs587784476 GRCh37 Chromosome 17, 73519765: 73519765
24 TSEN54 NM_207346.2(TSEN54): c.1335delC (p.Leu446Trpfs) deletion Pathogenic rs587784476 GRCh38 Chromosome 17, 75523684: 75523684
25 TSEN54 NM_207346.2(TSEN54): c.1511T> C (p.Leu504Pro) single nucleotide variant Likely pathogenic rs587784477 GRCh37 Chromosome 17, 73520423: 73520423
26 TSEN54 NM_207346.2(TSEN54): c.1511T> C (p.Leu504Pro) single nucleotide variant Likely pathogenic rs587784477 GRCh38 Chromosome 17, 75524342: 75524342

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 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
Content
Loading form....