MCID: PNT036
MIFTS: 40

Pontocerebellar Hypoplasia, Type 6

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

Aliases & Classifications for Pontocerebellar Hypoplasia, Type 6

MalaCards integrated aliases for Pontocerebellar Hypoplasia, Type 6:

Name: Pontocerebellar Hypoplasia, Type 6 57 13
Pontocerebellar Hypoplasia Type 6 12 53 59 29 6 44 15 73
Pch6 57 59 75
Fatal Infantile Encephalopathy with Mitochondrial Respiratory Chain Defects 59 75
Encephalopathy, Fatal Infantile, with Mitochondrial Respiratory Chain Defects 57
Encephalopathy Fatal Infantile with Mitochondrial Respiratory Chain Defects 53
Hypoplasia, Pontocerebellar, Type 6 40
Pontocerebellar Hypoplasia 6 75

Characteristics:

Orphanet epidemiological data:

59
pontocerebellar hypoplasia type 6
Inheritance: Autosomal recessive; Prevalence: <1/1000000 (Worldwide); Age of onset: Infancy,Neonatal; Age of death: early childhood;

OMIM:

57
Inheritance:
autosomal recessive

Miscellaneous:
variable severity
progressive disorder
death in childhood may occur
onset at birth or in first days or life


HPO:

32
pontocerebellar hypoplasia, type 6:
Onset and clinical course variable expressivity congenital onset progressive
Mortality/Aging death in childhood
Inheritance autosomal recessive inheritance


Classifications:



External Ids:

OMIM 57 611523
Disease Ontology 12 DOID:0060275
Orphanet 59 ORPHA166073
MESH via Orphanet 45 C548074
UMLS via Orphanet 74 C1969084
ICD10 via Orphanet 34 Q04.3
MedGen 42 C1969084
UMLS 73 C1969084

Summaries for Pontocerebellar Hypoplasia, Type 6

NIH Rare Diseases : 53 The following summary is from Orphanet, a European reference portal for information on rare diseases and orphan drugs.Orpha Number: 166073Disease definitionPontocerebellar hypoplasia type 6 (PCH6) is a rare form of pontocerebellar hypoplasia (see this term) characterized clinically at birth by hypotonia, clonus, epilepsy impaired swallowing and from infancy by progressive microencephaly, spasticity and lactic acidosis.EpidemiologyPCH6 is reported in less than 10 cases to dateClinical descriptionPCH6 is characterized clinically at birth by generalized hypotonia, lethargy and dysphagia. The clinical profile is characterized from infancy by a profound developmental delay, progressive microencephaly, hypotonia or spasticity treatment-resistant epilepsy.EtiologyPCH6 is caused by missense and splice site mutations in the mitochondrial arginyl-transfer RNA synthetase (RARS2) gene located to 6q16.1.Diagnostic methodsMRI demonstrates neocortical and more severe cerebral cortical atrophy (more severe than in other types of PCH), pontocerebellar hypoplasia with pons and cerebellum are equally affected. RARS2 mutation positive PCH6 patients can be screened by analysis of increased lactate in blood and cerebrospinal fluid. Biochemical analysis in muscle may demonstrate reduced activity of mitochondrial complexes I, III, and IV and normal activity of mitochondrial complex II.PrognosisPrognosis is poor, exact life expectancy is unknown but in most cases does not exceed infancy.Visit the Orphanet disease page for more resources.

MalaCards based summary : Pontocerebellar Hypoplasia, Type 6, also known as pontocerebellar hypoplasia type 6, is related to pontocerebellar hypoplasia and pontocerebellar hypoplasia, type 1a, and has symptoms including apnea and seizures. An important gene associated with Pontocerebellar Hypoplasia, Type 6 is RARS2 (Arginyl-TRNA Synthetase 2, Mitochondrial), and among its related pathways/superpathways is tRNA processing. Affiliated tissues include cerebellum, pons and eye, and related phenotypes are seizures and hyperreflexia

OMIM : 57 Pontocerebellar hypoplasia (PCH) is a heterogeneous group of disorders characterized by an abnormally small cerebellum and brainstem and associated with severe developmental delay (Edvardson et al., 2007). For a phenotypic description and a discussion of genetic heterogeneity of PCH, see PCH1 (607596). (611523)

UniProtKB/Swiss-Prot : 75 Pontocerebellar hypoplasia 6: A disorder characterized by an abnormally small cerebellum and brainstem, infantile encephalopathy, generalized hypotonia, lethargy and poor feeding. Recurrent apnea, intractable seizures occur early in the course of this condition.

Related Diseases for Pontocerebellar Hypoplasia, Type 6

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

Diseases related to Pontocerebellar Hypoplasia, Type 6 via text searches within MalaCards or GeneCards Suite gene sharing:

(show all 12)
# Related Disease Score Top Affiliating Genes
1 pontocerebellar hypoplasia 28.0 RARS2 TSEN2 TSEN34 TSEN54 VRK1
2 pontocerebellar hypoplasia, type 1a 10.9
3 hydrops fetalis, nonimmune, and/or atrial septal defect 10.0
4 fetal edema 10.0
5 hydrops fetalis 10.0
6 encephalopathy 10.0
7 pontocerebellar hypoplasia, type 5 9.6 TSEN54 VRK1
8 pontocerebellar hypoplasia, type 2e 9.4 TSEN2 TSEN34 TSEN54
9 pontocerebellar hypoplasia type 1 9.3 RARS2 TSEN54 VRK1
10 microcephaly 8.4 TSEN2 TSEN34 TSEN54 VRK1
11 trehalase deficiency 8.2 KCNQ2 RARS2 TSEN54 VRK1
12 pontoneocerebellar hypoplasia 7.9 ORC3 RARS2 TSEN2 TSEN34 TSEN54 VRK1

Graphical network of the top 20 diseases related to Pontocerebellar Hypoplasia, Type 6:



Diseases related to Pontocerebellar Hypoplasia, Type 6

Symptoms & Phenotypes for Pontocerebellar Hypoplasia, Type 6

Symptoms via clinical synopsis from OMIM:

57
Neurologic Central Nervous System:
seizures
hyperreflexia
cerebellar atrophy
cerebral atrophy
poor head control
more
Head And Neck Mouth:
narrow palate

Laboratory Abnormalities:
increased serum lactate
increased csf lactate

Muscle Soft Tissue:
hypotonia
edematous hands and feet (1 patient)
reduced activity of mitochondrial respiratory chains (1 family)

Head And Neck Face:
bitemporal narrowing
dysmorphic features described in 1 patient

Respiratory:
apneic episodes

Growth Other:
failure to thrive

Abdomen Gastrointestinal:
feeding difficulties
poor sucking

Head And Neck Nose:
prominent nasal bridge

Head And Neck Eyes:
deep-set eyes
dysconjugate eye movements

Head And Neck Head:
microcephaly, progressive


Clinical features from OMIM:

611523

Human phenotypes related to Pontocerebellar Hypoplasia, Type 6:

32 (show all 22)
# Description HPO Frequency HPO Source Accession
1 seizures 32 HP:0001250
2 hyperreflexia 32 HP:0001347
3 failure to thrive 32 HP:0001508
4 narrow palate 32 HP:0000189
5 global developmental delay 32 HP:0001263
6 absent speech 32 HP:0001344
7 apnea 32 HP:0002104
8 increased serum lactate 32 HP:0002151
9 prominent nasal bridge 32 HP:0000426
10 cerebellar hypoplasia 32 HP:0001321
11 deeply set eye 32 HP:0000490
12 cerebellar atrophy 32 HP:0001272
13 lower limb spasticity 32 HP:0002061
14 atrophy/degeneration affecting the brainstem 32 HP:0007366
15 cerebral atrophy 32 HP:0002059
16 poor suck 32 HP:0002033
17 generalized hypotonia 32 HP:0001290
18 poor head control 32 HP:0002421
19 increased csf lactate 32 HP:0002490
20 narrow forehead 32 HP:0000341
21 progressive microcephaly 32 HP:0000253
22 upper limb spasticity 32 HP:0006986

UMLS symptoms related to Pontocerebellar Hypoplasia, Type 6:


apnea, seizures

Drugs & Therapeutics for Pontocerebellar Hypoplasia, Type 6

Search Clinical Trials , NIH Clinical Center for Pontocerebellar Hypoplasia, Type 6

Cochrane evidence based reviews: pontocerebellar hypoplasia type 6

Genetic Tests for Pontocerebellar Hypoplasia, Type 6

Genetic tests related to Pontocerebellar Hypoplasia, Type 6:

# Genetic test Affiliating Genes
1 Pontocerebellar Hypoplasia Type 6 29 RARS2

Anatomical Context for Pontocerebellar Hypoplasia, Type 6

MalaCards organs/tissues related to Pontocerebellar Hypoplasia, Type 6:

41
Cerebellum, Pons, Eye, Brain

Publications for Pontocerebellar Hypoplasia, Type 6

Articles related to Pontocerebellar Hypoplasia, Type 6:

# Title Authors Year
1
RARS2 Mutations: Is Pontocerebellar Hypoplasia Type 6 a Mitochondrial Encephalopathy? ( 27683254 )
2016
2
Neuropathologic Characterization of Pontocerebellar Hypoplasia Type 6 Associated With Cardiomyopathy and Hydrops Fetalis and Severe Multisystem Respiratory Chain Deficiency due to Novel RARS2 Mutations. ( 26083569 )
2015
3
Neuropathologic features of pontocerebellar hypoplasia type 6. ( 25289895 )
2014
4
Pontocerebellar hypoplasia type 6 caused by mutations in RARS2: definition of the clinical spectrum and molecular findings in five patients. ( 22569581 )
2013
5
Further delineation of pontocerebellar hypoplasia type 6 due to mutations in the gene encoding mitochondrial arginyl-tRNA synthetase, RARS2. ( 22086604 )
2012
6
Pontocerebellar hypoplasia type 6: A British case with PEHO-like features. ( 20635367 )
2010

Variations for Pontocerebellar Hypoplasia, Type 6

ClinVar genetic disease variations for Pontocerebellar Hypoplasia, Type 6:

6
(show all 18)
# Gene Variation Type Significance SNP ID Assembly Location
1 RARS2 RARS2, IVS2, A-G, +5 single nucleotide variant Pathogenic
2 RARS2 NM_020320.4(RARS2): c.1024A> G (p.Met342Val) single nucleotide variant Pathogenic rs387907048 GRCh37 Chromosome 6, 88231193: 88231193
3 RARS2 NM_020320.4(RARS2): c.1024A> G (p.Met342Val) single nucleotide variant Pathogenic rs387907048 GRCh38 Chromosome 6, 87521475: 87521475
4 RARS2 RARS2, -2A-G single nucleotide variant Pathogenic
5 RARS2 NM_020320.4(RARS2): c.1054_1055delAA (p.Lys352Alafs) deletion Likely pathogenic rs797045911 GRCh37 Chromosome 6, 88229955: 88229956
6 RARS2 NM_020320.4(RARS2): c.1054_1055delAA (p.Lys352Alafs) deletion Likely pathogenic rs797045911 GRCh38 Chromosome 6, 87520237: 87520238
7 RARS2 NM_020320.4(RARS2): c.419T> G (p.Phe140Cys) single nucleotide variant Pathogenic/Likely pathogenic rs772887102 GRCh38 Chromosome 6, 87548623: 87548623
8 RARS2 NM_020320.4(RARS2): c.419T> G (p.Phe140Cys) single nucleotide variant Pathogenic/Likely pathogenic rs772887102 GRCh37 Chromosome 6, 88258341: 88258341
9 RARS2 NM_020320.4(RARS2): c.189delT (p.Gln64Lysfs) deletion Uncertain significance rs1085307089 GRCh37 Chromosome 6, 88273872: 88273872
10 RARS2 NM_020320.4(RARS2): c.189delT (p.Gln64Lysfs) deletion Uncertain significance rs1085307089 GRCh38 Chromosome 6, 87564154: 87564154
11 RARS2 NM_020320.4(RARS2): c.370delC (p.Gln124Argfs) deletion Likely pathogenic GRCh38 Chromosome 6, 87555433: 87555433
12 RARS2 NM_020320.4(RARS2): c.370delC (p.Gln124Argfs) deletion Likely pathogenic GRCh37 Chromosome 6, 88265151: 88265151
13 RARS2 NM_020320.4(RARS2): c.1544A> G (p.Asp515Gly) single nucleotide variant Likely pathogenic rs765088174 GRCh37 Chromosome 6, 88226566: 88226566
14 RARS2 NM_020320.4(RARS2): c.1544A> G (p.Asp515Gly) single nucleotide variant Likely pathogenic rs765088174 GRCh38 Chromosome 6, 87516848: 87516848
15 RARS2 NM_020320.4(RARS2): c.1237+1G> A single nucleotide variant Pathogenic rs759922477 GRCh37 Chromosome 6, 88229300: 88229300
16 RARS2 NM_020320.4(RARS2): c.1237+1G> A single nucleotide variant Pathogenic rs759922477 GRCh38 Chromosome 6, 87519582: 87519582
17 RARS2 NM_020320.4(RARS2): c.1612delA (p.Thr538Hisfs) deletion Pathogenic rs781417096 GRCh38 Chromosome 6, 87514995: 87514995
18 RARS2 NM_020320.4(RARS2): c.1612delA (p.Thr538Hisfs) deletion Pathogenic rs781417096 GRCh37 Chromosome 6, 88224713: 88224713

Expression for Pontocerebellar Hypoplasia, Type 6

Search GEO for disease gene expression data for Pontocerebellar Hypoplasia, Type 6.

Pathways for Pontocerebellar Hypoplasia, Type 6

Pathways related to Pontocerebellar Hypoplasia, Type 6 according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.17 TSEN2 TSEN34 TSEN54

GO Terms for Pontocerebellar Hypoplasia, Type 6

Cellular components related to Pontocerebellar Hypoplasia, Type 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nucleolus GO:0005730 9.26 TSEN2 TSEN34 TSEN54 VRK1
2 tRNA-intron endonuclease complex GO:0000214 8.8 TSEN2 TSEN34 TSEN54

Biological processes related to Pontocerebellar Hypoplasia, Type 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mRNA processing GO:0006397 9.54 TSEN2 TSEN34 TSEN54
2 tRNA processing GO:0008033 9.5 TSEN2 TSEN34 TSEN54
3 RNA phosphodiester bond hydrolysis, endonucleolytic GO:0090502 9.43 TSEN2 TSEN34 TSEN54
4 nucleic acid phosphodiester bond hydrolysis GO:0090305 9.4 TSEN2 TSEN34
5 RNA phosphodiester bond hydrolysis GO:0090501 9.33 TSEN2 TSEN34 TSEN54
6 tRNA splicing, via endonucleolytic cleavage and ligation GO:0006388 9.13 TSEN2 TSEN34 TSEN54
7 tRNA-type intron splice site recognition and cleavage GO:0000379 8.8 TSEN2 TSEN34 TSEN54

Molecular functions related to Pontocerebellar Hypoplasia, Type 6 according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 nuclease activity GO:0004518 9.16 TSEN2 TSEN34
2 endonuclease activity GO:0004519 8.96 TSEN2 TSEN34
3 tRNA-intron endonuclease activity GO:0000213 8.8 TSEN2 TSEN34 TSEN54

Sources for Pontocerebellar Hypoplasia, Type 6

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
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