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MCID: CHR095
MIFTS: 47

Chronic Progressive External Ophthalmoplegia

Categories: Eye diseases, Metabolic diseases, Muscle diseases, Neuronal diseases, Rare diseases
Genes Variations Tissues Related diseases Publications Pathways Symptoms & Phenotypes Drugs
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Aliases & Classifications for Chronic Progressive External Ophthalmoplegia

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MalaCards integrated aliases for Chronic Progressive External Ophthalmoplegia:

Name: Chronic Progressive External Ophthalmoplegia 12 54 26 15 74
Progressive External Ophthalmoplegia 12 77 54 26 38 30 56 6 17
Cpeo 54 26
Ophthalmoplegia, External, Progressive, Chronic 41
Ophthalmoplegia, Chronic Progressive External 45
Peo 26

Classifications:

MalaCards categories:
Global: Rare diseases Metabolic diseases
Anatomical: Eye diseases Muscle diseases Neuronal diseases
See all MalaCards categories (disease lists)
ICD10: 34


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Disease Ontology 12 DOID:12558
KEGG 38 H01118
ICD9CM 36 378.72
MeSH 45 D017246
SNOMED-CT 69 46252003
ICD10 34 H49.4
UMLS 74 C0162674
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Summaries for Chronic Progressive External Ophthalmoplegia

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Genetics Home Reference : 26 Progressive external ophthalmoplegia is a condition characterized by weakness of the eye muscles. The condition typically appears in adults between ages 18 and 40 and slowly worsens over time. The first sign of progressive external ophthalmoplegia is typically drooping eyelids (ptosis), which can affect one or both eyelids. As ptosis worsens, affected individuals may use the forehead muscles to try to lift the eyelids, or they may lift up their chin in order to see. Another characteristic feature of progressive external ophthalmoplegia is weakness or paralysis of the muscles that move the eye (ophthalmoplegia). Affected individuals have to turn their head to see in different directions, especially as the ophthalmoplegia worsens. People with progressive external ophthalmoplegia may also have general weakness of the muscles used for movement (myopathy), particularly those in the neck, arms, or legs. The weakness may be especially noticeable during exercise (exercise intolerance). Muscle weakness may also cause difficulty swallowing (dysphagia).

MalaCards based summary : Chronic Progressive External Ophthalmoplegia, also known as progressive external ophthalmoplegia, is related to autosomal dominant progressive external ophthalmoplegia and kearns-sayre syndrome, and has symptoms including ophthalmoplegia An important gene associated with Chronic Progressive External Ophthalmoplegia is TWNK (Twinkle MtDNA Helicase), and among its related pathways/superpathways are tRNA Aminoacylation and Nucleotide Metabolism. The drugs Nicotinamide and Niacin have been mentioned in the context of this disorder. Affiliated tissues include eye, skeletal muscle and pancreas, and related phenotype is cellular.

NIH Rare Diseases : 54 Chronic progressive external ophthalmoplegia (CPEO) is a condition characterized mainly by a loss of the muscle functions involved in eye and eyelid movement. Signs and symptoms tend to begin in early adulthood and most commonly include weakness or paralysis of the muscles that move the eye (ophthalmoplegia) and drooping of the eyelids (ptosis). Some affected individuals also have general weakness of the skeletal muscles (myopathy), which may be especially noticeable during exercise. Muscle weakness may also cause difficulty swallowing (dysphagia). CPEO can be caused by mutations in any of several genes, which may be located in mitochondrial DNA or nuclear DNA. It has different inheritance patterns depending on the gene involved in the affected individual. CPEO can occur as part of other underlying conditions, such as ataxia neuropathy spectrum and Kearns-Sayre syndrome. These conditions may not only involve CPEO, but various additional features that are not shared by most individuals with CPEO.

Wikipedia : 77 Chronic progressive external ophthalmoplegia (CPEO), also known as progressive external ophthalmoplegia... more...

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Related Diseases for Chronic Progressive External Ophthalmoplegia

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Diseases in the Total Internal Ophthalmoplegia family:

Chronic Progressive External Ophthalmoplegia Autosomal Dominant Progressive External Ophthalmoplegia

Diseases related to Chronic Progressive External Ophthalmoplegia via text searches within MalaCards or GeneCards Suite gene sharing:

(show top 50) (show all 117)
# Related Disease Score Top Affiliating Genes
1 autosomal dominant progressive external ophthalmoplegia 33.0 POLG POLG2 RRM2B SLC25A4 TWNK
2 kearns-sayre syndrome 32.1 COX5A POLG RRM2B SLC25A4 TWNK TYMP
3 mitochondrial dna depletion syndrome 7 32.0 SLC25A4 TWNK
4 mitochondrial dna depletion syndrome 1 32.0 POLG TYMP
5 sensory ataxic neuropathy, dysarthria, and ophthalmoparesis 30.3 POLG TWNK
6 ptosis 30.2 POLG RRM2B TYMP
7 mitochondrial disorders 30.1 COX5A SLC25A4
8 mitochondrial myopathy 29.7 COX5A MT-TA MT-TL2 POLG SLC25A4
9 mitochondrial dna depletion syndrome 4a 29.7 POLG POLG2 TWNK TYMP
10 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 29.7 POLG TWNK TYMP
11 mitochondrial neurogastrointestinal encephalomyopathy 29.4 POLG RRM2B TYMP
12 mitochondrial metabolism disease 27.7 COX5A MT-TL2 POLG POLG2 RRM2B SLC25A4
13 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 3 12.8
14 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 5 12.8
15 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 4 12.7
16 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 6 12.7
17 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 5 12.7
18 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 1 12.0
19 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 2 12.0
20 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 3 12.0
21 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 4 12.0
22 mitochondrial dna depletion syndrome 11 11.9
23 ocular muscular dystrophy 11.9
24 mitochondrial dna-related progressive external ophthalmoplegia 11.8
25 gaze palsy, familial horizontal, with progressive scoliosis 1 11.7
26 mitochondrial dna depletion syndrome 4b 11.7
27 strabismus 11.6
28 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 1 11.6
29 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 2 11.4
30 horizontal gaze palsy with progressive scoliosis 11.3
31 optic atrophy with or without deafness, ophthalmoplegia, myopathy, ataxia, and neuropathy 11.3
32 combined oxidative phosphorylation deficiency 33 11.3
33 optic atrophy 1 11.2
34 combined oxidative phosphorylation deficiency 20 11.2
35 myopathy 10.4
36 muscle disorders 10.3
37 mechanical strabismus 10.3
38 ataxia neuropathy spectrum 10.2 POLG TWNK
39 optic nerve disease 10.2
40 neuropathy 10.2
41 intraocular pressure quantitative trait locus 10.2
42 isolated optic neuritis 10.2
43 hypogonadism 10.1
44 hypogonadotropism 10.1
45 tremor 10.1
46 multiple sclerosis 10.1
47 polyglucosan body myopathy 1 with or without immunodeficiency 10.1
48 ataxia, combined cerebellar and peripheral, with hearing loss and diabetes mellitus 10.1
49 alternating exotropia 10.1
50 exotropia 10.1

Graphical network of the top 20 diseases related to Chronic Progressive External Ophthalmoplegia:



Diseases related to Chronic Progressive External Ophthalmoplegia
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Symptoms & Phenotypes for Chronic Progressive External Ophthalmoplegia

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UMLS symptoms related to Chronic Progressive External Ophthalmoplegia:


ophthalmoplegia

MGI Mouse Phenotypes related to Chronic Progressive External Ophthalmoplegia:

47
# Description MGI Source Accession Score Top Affiliating Genes
1 cellular MP:0005384 9.17 HELLS POLG POLG2 RRM2B SLC25A4 TWNK
Sources

Drugs & Therapeutics for Chronic Progressive External Ophthalmoplegia

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Drugs for Chronic Progressive External Ophthalmoplegia (from DrugBank, HMDB, Dgidb, PharmGKB, IUPHAR, NovoSeek, BitterDB):

(show all 17)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Nicotinamide Approved, Investigational Not Applicable 98-92-0 936
2
Niacin Approved, Investigational, Nutraceutical Not Applicable 59-67-6 938
3
Folic Acid Approved, Nutraceutical, Vet_approved Not Applicable 59-30-3 6037
4 Nicotinic Acids Not Applicable
5 Antimetabolites Not Applicable
6 Vitamins Not Applicable
7 Trace Elements Not Applicable
8 Lipid Regulating Agents Not Applicable
9 Vitamin B Complex Not Applicable
10 Hypolipidemic Agents Not Applicable
11 Nutrients Not Applicable
12 Vitamin B3 Not Applicable
13 Vasodilator Agents Not Applicable
14 Vitamin B9 Not Applicable
15 Micronutrients Not Applicable
16 Folate Not Applicable
17 Ubiquinone

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 Mitochondrial nt3243 A>G Mutation in Taiwan Unknown status NCT02114554
2 MRI Study - Chronic Progressive External Ophthalmoplegia Completed NCT02161848
3 Nicotinamide Riboside and Mitochondrial Biogenesis Recruiting NCT03432871 Not Applicable
4 North American Mitochondrial Disease Consortium Patient Registry and Biorepository (NAMDC) Recruiting NCT01694940
5 Low Residue Diet Study in Mitochondrial Disease Recruiting NCT03388528 Not Applicable
6 Natural History of Pearson Syndrome Enrolling by invitation NCT02327364

Search NIH Clinical Center for Chronic Progressive External Ophthalmoplegia

Cochrane evidence based reviews: ophthalmoplegia, chronic progressive external

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Genetic Tests for Chronic Progressive External Ophthalmoplegia

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Genetic tests related to Chronic Progressive External Ophthalmoplegia:

# Genetic test Affiliating Genes
1 Progressive External Ophthalmoplegia 30
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Anatomical Context for Chronic Progressive External Ophthalmoplegia

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MalaCards organs/tissues related to Chronic Progressive External Ophthalmoplegia:

42
Eye, Skeletal Muscle, Pancreas, Retina, Skin, Brain, Heart
Sources

Publications for Chronic Progressive External Ophthalmoplegia

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Articles related to Chronic Progressive External Ophthalmoplegia:

(show top 50) (show all 314)
# Title Authors Year
1
Clinical and demographic features of chronic progressive external ophthalmoplegia in a large adult-onset cohort. ( 29246868 )
2019
2
Strabismus surgery for diplopia in chronic progressive external ophthalmoplegia. ( 29582258 )
2019
3
Teaching Video NeuroImages: MT-TL1 mutation presenting as chronic progressive external ophthalmoplegia. ( 30665919 )
2019
4
Distinct segregation of the pathogenic m.5667G>A mitochondrial tRNAAsn mutation in extraocular and skeletal muscle in chronic progressive external ophthalmoplegia. ( 30962064 )
2019
5
Focal Segmental Glomerulosclerosis Associated with Chronic Progressive External Ophthalmoplegia and Mitochondrial DNA A3243G Mutation. ( 29190634 )
2018
6
Intracranial hypotension mimicking chronic progressive external ophthalmoplegia. ( 29300676 )
2018
7
False positive acetylcholine receptor antibodies in a case of unilateral chronic progressive external ophthalmoplegia: case report and review of literature. ( 29333908 )
2018
8
Disclosing the functional changes of two genetic alterations in a patient with Chronic Progressive External Ophthalmoplegia: Report of the novel mtDNA m.7486G>A variant. ( 29398297 )
2018
9
Novel mutation in the RNASEH1 gene in a chronic progressive external ophthalmoplegia patient. ( 30340744 )
2018
10
Relapsing remitting multiple sclerosis in progressive external ophthalmoplegia: A report of two cases. ( 30557092 )
2018
11
Clinical commentary on 'Relapsing remitting multiple sclerosis in progressive external ophthalmoplegia: A report of two cases'. ( 30557095 )
2018
12
Dystonia in a Patient with Autosomal-Dominant Progressive External Ophthalmoplegia Type 1 Caused by Mutation in the POLG Gene. ( 30838265 )
2017
13
Sporadic chronic progressive external ophthalmoplegia with single large mitochondrial DNA deletion and neurogenic findings. ( 28175988 )
2017
14
Unilateral Ptosis and Homolateral Hemifacial Weakness in Chronic Progressive External Ophthalmoplegia. ( 28512510 )
2017
15
RE: "Unilateral Ptosis and Homolateral Hemifacial Weakness in Chronic Progressive External Ophthalmoplegia". ( 28533811 )
2017
16
Nerve excitability changes related to muscle weakness in chronic progressive external ophthalmoplegia. ( 28535487 )
2017
17
Axonal hyperexcitability due to Schwann cell involvement in chronic progressive external ophthalmoplegia. ( 28811105 )
2017
18
Reply to "Axonal hyperexcitability due to Schwann cell involvement in chronic progressive external ophthalmoplegia". ( 28838816 )
2017
19
Surgical Technique for Pulled in Two Syndrome: Three Cases With Chronic Progressive External Ophthalmoplegia. ( 29156062 )
2017
20
Mitochondrial mutations in 12S rRNA and 16S rRNA presenting as chronic progressive external ophthalmoplegia (CPEO) plus: A case report. ( 29310369 )
2017
21
Reply to: "Peculiarities of progressive external ophthalmoplegia due to single mtDNA deletions". ( 28359601 )
2017
22
C10ORF2 mutation associated with progressive external ophthalmoplegia and clinically isolated syndrome. ( 28528470 )
2017
23
Opening One's Eyes to Mosaicism in Progressive External Ophthalmoplegia. ( 29264394 )
2017
24
Novel mutation in C10orf2 associated with multiple mtDNA deletions, chronic progressive external ophthalmoplegia and premature aging. ( 26689116 )
2016
25
A novel mitochondrial tRNA(Ala) gene variant causes chronic progressive external ophthalmoplegia in a patient with Huntington disease. ( 27014581 )
2016
26
Chronic Progressive External Ophthalmoplegia in the Absence of Ptosis. ( 27111092 )
2016
27
Multiple sclerosis and chronic progressive external ophthalmoplegia associated with a large scale mitochondrial DNA single deletion. ( 27113600 )
2016
28
Histopathological and genetic analysis of extraocular muscle in chronic progressive external ophthalmoplegia. ( 27470685 )
2016
29
Late-Onset Development of Eyelid Ptosis in Chronic Progressive External Ophthalmoplegia: A 30-Year Follow-up. ( 27928383 )
2016
30
Mutation in TWINKLE in a Large Iranian Family with Progressive External Ophthalmoplegia, Myopathy, Dysphagia and Dysphonia, and Behavior Change. ( 26838077 )
2016
31
Double trouble progressive external ophthalmoplegia and Huntington's disease. ( 27144127 )
2016
32
Reply to: Double trouble progressive external ophthalmoplegia and Huntington's disease. ( 27331008 )
2016
33
Progressive External Ophthalmoplegia. ( 27072953 )
2016
34
Peculiarities of progressive external ophthalmoplegia due to single mitochondrial DNA deletions. ( 27814938 )
2016
35
Pharyngeal transit in patients with chronic progressive external ophthalmoplegia. ( 25142449 )
2015
36
Vocal cord palsy in a case of chronic progressive external ophthalmoplegia. ( 26713034 )
2015
37
Twinkle mutations in two Chinese families with autosomal dominant progressive external ophthalmoplegia. ( 24091712 )
2014
38
No association between mitochondrial tRNA(Val) T1658C mutation and chronic progressive external ophthalmoplegia (CPEO). ( 23815321 )
2014
39
Mutations in the SPG7 gene cause chronic progressive external ophthalmoplegia through disordered mitochondrial DNA maintenance. ( 24727571 )
2014
40
Novel mitochondrial tRNA(Ile) m.4282A>G gene mutation leads to chronic progressive external ophthalmoplegia plus phenotype. ( 25034047 )
2014
41
Cardiac involvement in chronic progressive external ophthalmoplegia. ( 25139213 )
2014
42
Selected case from the Arkadi M. Rywlin International Pathology Slide Series: Mitochondrial myopathy presenting with chronic progressive external ophthalmoplegia (CPEO): a case report. ( 25299315 )
2014
43
Chronic progressive external ophthalmoplegia with inflammatory myopathy. ( 25674260 )
2014
44
Multiple deletions in mitochondrial DNA in a patient with progressive external ophthalmoplegia, leukoencephalopathy and hypogonadism. ( 24930659 )
2014
45
[Retinal ganglion cell layer and visual function in patients with progressive external ophthalmoplegia caused by common mtDNA deletion]. ( 25518262 )
2014
46
Chronic progressive external ophthalmoplegia coexistent with motor neuron disease in a patient with a novel large-scale mitochondrial DNA deletion. ( 23266267 )
2013
47
Autosomal dominant mutations in POLG and C10orf2: association with late onset chronic progressive external ophthalmoplegia and Parkinsonism in two patients. ( 23719791 )
2013
48
Extraocular muscle atrophy and central nervous system involvement in chronic progressive external ophthalmoplegia. ( 24086434 )
2013
49
Orthostatic tremor, progressive external ophthalmoplegia, and Twinkle. ( 24061067 )
2013
50
Subnormal levels of POLγA cause inefficient initiation of light-strand DNA synthesis and lead to mitochondrial DNA deletions and progressive external ophthalmoplegia [corrected]. ( 23446635 )
2013
Sources

Variations for Chronic Progressive External Ophthalmoplegia

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ClinVar genetic disease variations for Chronic Progressive External Ophthalmoplegia:

6
# Gene Variation Type Significance SNP ID Assembly Location
1 RRM2B NM_015713.4(RRM2B): c.606T> A (p.Phe202Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs515726194 GRCh37 Chromosome 8, 103231120: 103231120
2 RRM2B NM_015713.4(RRM2B): c.606T> A (p.Phe202Leu) single nucleotide variant Conflicting interpretations of pathogenicity rs515726194 GRCh38 Chromosome 8, 102218892: 102218892
3 RRM2B NM_015713.4(RRM2B): c.817G> A (p.Gly273Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs387906891 GRCh37 Chromosome 8, 103225090: 103225090
4 RRM2B NM_015713.4(RRM2B): c.817G> A (p.Gly273Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs387906891 GRCh38 Chromosome 8, 102212862: 102212862
5 RRM2B NM_015713.4(RRM2B): c.97C> T (p.Pro33Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs387906892 GRCh37 Chromosome 8, 103244484: 103244484
6 RRM2B NM_015713.4(RRM2B): c.97C> T (p.Pro33Ser) single nucleotide variant Conflicting interpretations of pathogenicity rs387906892 GRCh38 Chromosome 8, 102232256: 102232256
7 MT-TS1 NC_012920.1: m.7486G> A single nucleotide variant Uncertain significance rs1556423295 GRCh37 Chromosome MT, 7486: 7486
8 MT-TS1 NC_012920.1: m.7486G> A single nucleotide variant Uncertain significance rs1556423295 GRCh38 Chromosome MT, 7486: 7486
9 TWNK NM_021830.4(TWNK): c.1121G> A (p.Arg374Gln) single nucleotide variant Pathogenic/Likely pathogenic rs1554887097 GRCh37 Chromosome 10, 102749088: 102749088
10 TWNK NM_021830.4(TWNK): c.1121G> A (p.Arg374Gln) single nucleotide variant Pathogenic/Likely pathogenic rs1554887097 GRCh38 Chromosome 10, 100989331: 100989331
Sources

Expression for Chronic Progressive External Ophthalmoplegia

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Search GEO for disease gene expression data for Chronic Progressive External Ophthalmoplegia.
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Pathways for Chronic Progressive External Ophthalmoplegia

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Pathways related to Chronic Progressive External Ophthalmoplegia according to GeneCards Suite gene sharing:

# Super pathways Score Top Affiliating Genes
1
tRNA Aminoacylation 67
Show member pathways
 11.37 MT-TA MT-TI MT-TL2
2
Nucleotide Metabolism 1
9.9 POLG RRM2B
Sources

GO Terms for Chronic Progressive External Ophthalmoplegia

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Cellular components related to Chronic Progressive External Ophthalmoplegia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 mitochondrion GO:0005739 9.5 COX5A POLG POLG2 RRM2B SLC25A4 SPG7
2 mitochondrial nucleoid GO:0042645 8.8 POLG POLG2 TWNK

Biological processes related to Chronic Progressive External Ophthalmoplegia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 cellular response to glucose stimulus GO:0071333 9.4 POLG TWNK
2 DNA biosynthetic process GO:0071897 9.37 POLG POLG2
3 mitochondrion organization GO:0007005 9.33 POLG2 SPG7 TWNK
4 DNA-dependent DNA replication GO:0006261 9.32 POLG POLG2
5 mitochondrial genome maintenance GO:0000002 9.26 SLC25A4 TYMP
6 DNA replication GO:0006260 9.26 POLG POLG2 RRM2B TWNK
7 mitochondrial DNA replication GO:0006264 8.92 POLG POLG2 RRM2B TWNK

Molecular functions related to Chronic Progressive External Ophthalmoplegia according to GeneCards Suite gene sharing:

# Name GO ID Score Top Affiliating Genes
1 DNA-directed DNA polymerase activity GO:0003887 8.62 POLG POLG2
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Sources for Chronic Progressive External Ophthalmoplegia

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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
The MalaCards human disease database index: 1-9 A B C D E F G H I J K L M N O P Q R S T U V W X Y Z
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