PEO
MCID: CHR095
MIFTS: 46

Chronic Progressive External Ophthalmoplegia (PEO)

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

Aliases & Classifications for Chronic Progressive External Ophthalmoplegia

MalaCards integrated aliases for Chronic Progressive External Ophthalmoplegia:

Name: Chronic Progressive External Ophthalmoplegia 12 53 25 15 72
Progressive External Ophthalmoplegia 12 75 53 25 59 37 29 55 6 17 33
Cpeo 53 25
Ophthalmoplegia, External, Progressive, Chronic 40
Ophthalmoplegia, Chronic Progressive External 44
Peo 25

Classifications:

Orphanet: 59  
Rare eye diseases


External Ids:

Disease Ontology 12 DOID:12558
KEGG 37 H01118
ICD9CM 35 378.72
MeSH 44 D017246
SNOMED-CT 68 46252003
ICD10 33 H49.4
Orphanet 59 ORPHA520820
UMLS 72 C0162674

Summaries for Chronic Progressive External Ophthalmoplegia

Genetics Home Reference : 25 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). When the muscle cells of affected individuals are stained and viewed under a microscope, these cells usually appear abnormal. These abnormal muscle cells contain an excess of cell structures called mitochondria and are known as ragged-red fibers. Although muscle weakness is the primary symptom of progressive external ophthalmoplegia, this condition can be accompanied by other signs and symptoms. In these instances, the condition is referred to as progressive external ophthalmoplegia plus (PEO+). Additional signs and symptoms can include hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss), weakness and loss of sensation in the limbs due to nerve damage (neuropathy), impaired muscle coordination (ataxia), a pattern of movement abnormalities known as parkinsonism, and depression. Progressive external ophthalmoplegia is part of a spectrum of disorders with overlapping signs and symptoms. Similar disorders include ataxia neuropathy spectrum and Kearns-Sayre syndrome. Like progressive external ophthalmoplegia, the other conditions in this spectrum can involve weakness of the eye muscles. However, these conditions have many additional features not shared by most people with progressive external ophthalmoplegia.

MalaCards based summary : Chronic Progressive External Ophthalmoplegia, also known as progressive external ophthalmoplegia, is related to mitochondrial dna depletion syndrome 7 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 is tRNA Aminoacylation. The drugs Cysteamine and Nicotinamide have been mentioned in the context of this disorder. Affiliated tissues include eye, skeletal muscle and heart.

NIH Rare Diseases : 53 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.

KEGG : 37
Progressive external ophthalmoplegia (PEO) is a a progressive weakness of the external muscles of the eye resulting in blepharoptosis and ophthalmoparesis. Often other muscles are involved resulting in dysphagia and a variable neck and limb muscle weakness. Most sporadic PEO cases have an acquired genetic disease with a heteroplasmic large deletion of mitochondrial DNA (mtDNA) in muscle. In familial PEO, several modes of inheritance occur. Patients may have a nuclear gene defect that predisposes to the accumulation of mtDNA deletions. Recently, mutations in such nuclear genes have been discovered. Some mutations are dominant (PEOA) and others recessive.

Wikipedia : 75 Chronic progressive external ophthalmoplegia (CPEO), is a type of eye disorder characterized by slowly... more...

Related Diseases for Chronic Progressive External Ophthalmoplegia

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 215)
# Related Disease Score Top Affiliating Genes
1 mitochondrial dna depletion syndrome 7 32.6 TWNK SLC25A4
2 kearns-sayre syndrome 31.9 TYMP TWNK SLC25A4 POLG COX5A
3 mitochondrial dna depletion syndrome 1 31.6 TYMP POLG MT-TK
4 mitochondrial disorders 31.1 SLC25A4 COX5A
5 mitochondrial encephalomyopathy 30.7 MT-TL2 MT-TK COX5A
6 mitochondrial dna depletion syndrome 30.6 TWNK POLG
7 ataxia neuropathy spectrum 30.5 TWNK POLG
8 sensory ataxic neuropathy, dysarthria, and ophthalmoparesis 30.4 TWNK POLG
9 axonal neuropathy 29.9 TWNK SLC25A4 POLG
10 mitochondrial myopathy 29.8 SLC25A4 POLG MT-TL2 MT-TA COX5A
11 leigh syndrome 29.5 POLG MT-TK MT-TI COX5A
12 mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes 29.5 TYMP TWNK POLG
13 mitochondrial neurogastrointestinal encephalomyopathy 29.3 TYMP POLG MT-TK
14 mitochondrial dna depletion syndrome 4a 29.0 TYMP TWNK POLG2 POLG
15 autosomal dominant progressive external ophthalmoplegia 28.9 TWNK SLC25A4 POLG2 POLG
16 muscular disease 28.7 TWNK SLC25A4 POLG2 POLG
17 mitochondrial metabolism disease 27.0 TYMP TWNK SPG7 SLC25A4 POLG2 POLG
18 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 4 13.0
19 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 6 13.0
20 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 3 12.9
21 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 5 12.9
22 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 5 12.9
23 mitochondrial dna depletion syndrome 11 12.2
24 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 1 12.1
25 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 2 12.1
26 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 3 12.1
27 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal dominant 4 12.1
28 gaze palsy, familial horizontal, with progressive scoliosis 1 12.0
29 ocular muscular dystrophy 11.9
30 mitochondrial dna-related progressive external ophthalmoplegia 11.9
31 mitochondrial dna depletion syndrome 4b 11.8
32 strabismus 11.7
33 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 1 11.7
34 progressive external ophthalmoplegia with mitochondrial dna deletions, autosomal recessive 2 11.6
35 horizontal gaze palsy with progressive scoliosis 11.5
36 combined oxidative phosphorylation deficiency 33 11.4
37 mitochondrial dna depletion syndrome 2 11.3
38 combined oxidative phosphorylation deficiency 20 11.3
39 ptosis 10.8
40 myopathy 10.8
41 dysphagia 10.5
42 mechanical strabismus 10.4
43 branchiootic syndrome 1 10.4
44 neuropathy 10.4
45 polg-related disorders 10.3
46 ataxia and polyneuropathy, adult-onset 10.3
47 optic nerve disease 10.3
48 lactic acidosis 10.3
49 myasthenia gravis 10.3
50 retinitis pigmentosa 10.3

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



Diseases related to Chronic Progressive External Ophthalmoplegia

Symptoms & Phenotypes for Chronic Progressive External Ophthalmoplegia

UMLS symptoms related to Chronic Progressive External Ophthalmoplegia:


ophthalmoplegia

Drugs & Therapeutics for Chronic Progressive External Ophthalmoplegia

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

(show all 18)
# Name Status Phase Clinical Trials Cas Number PubChem Id
1
Cysteamine Approved, Investigational Phase 2 60-23-1 6058
2
Nicotinamide Approved, Investigational 98-92-0 936
3
Folic acid Approved, Nutraceutical, Vet_approved 59-30-3 6037
4
Niacin Approved, Investigational, Nutraceutical 59-67-6 938
5 Ubiquinone
6 Micronutrients
7 Trace Elements
8 Lipid Regulating Agents
9 Vitamins
10 Vitamin B Complex
11 Vitamin B9
12 Folate
13 Vitamin B3
14 Nicotinic Acids
15 Nutrients
16 Hypolipidemic Agents
17 Vasodilator Agents
18 Antimetabolites

Interventional clinical trials:


# Name Status NCT ID Phase Drugs
1 A Long-Term Open-Label Extension Study of RP103-MITO-001 to Assess the Safety, Tolerability and Efficacy of Cysteamine Bitartrate Delayed-release Capsules (RP103) for Treatment of Children With Inherited Mitochondrial Disease Terminated NCT02473445 Phase 2 Cysteamine Bitartrate
2 A Phase Ia/Ib, Multiple-site Study to Assess the Safety, Tolerability, Pharmacokinetics, and Pharmacodynamics of KL1333 After a Single and Multiple Ascending Oral Doses in Healthy Subjects and Patients With Primary Mitochondrial Disease Recruiting NCT03888716 Phase 1 KL1333;Placebo Oral Tablet
3 Clinical Characteristics and Prognostic Factors of Mitochondrial nt3243 A>G Mutation in Taiwan Unknown status NCT02114554
4 Magnetic Resonance Imaging Study of Patients With Chronic Progressive External Ophthalmoplegia Completed NCT02161848
5 Can Metagenomic and Metadata be Combined Using Bioinformatics and Computational Biology Methods to Personalise Patient Treatment. Completed NCT03213067
6 The Effect of Niacin Supplementation on Systemic Nicotinamide Adenine Dinucleotide (NAD+) Metabolism, Physiology and Muscle Performance in Healthy Controls and Mitochondrial Myopathy Patients Completed NCT03973203
7 North American Mitochondrial Disease Consortium Patient Registry and Biorepository (NAMDC) Recruiting NCT01694940
8 The Role of Nicotinamide Riboside in Mitochondrial Biogenesis Recruiting NCT03432871
9 Genetic Studies of Strabismus, Congenital Cranial Dysinnervation Disorders (CCDDs), and Their Associated Anomalies Recruiting NCT03059420
10 Rare Disease Clinical Research Network Natural History of Pearson Syndrome North American Mitochondrial Disease Consortium (NAMDC) Enrolling by invitation NCT02327364

Search NIH Clinical Center for Chronic Progressive External Ophthalmoplegia

Cochrane evidence based reviews: ophthalmoplegia, chronic progressive external

Genetic Tests for Chronic Progressive External Ophthalmoplegia

Genetic tests related to Chronic Progressive External Ophthalmoplegia:

# Genetic test Affiliating Genes
1 Progressive External Ophthalmoplegia 29

Anatomical Context for Chronic Progressive External Ophthalmoplegia

MalaCards organs/tissues related to Chronic Progressive External Ophthalmoplegia:

41
Eye, Skeletal Muscle, Heart, Brain, Retina, Thyroid, Liver

Publications for Chronic Progressive External Ophthalmoplegia

Articles related to Chronic Progressive External Ophthalmoplegia:

(show top 50) (show all 1024)
# Title Authors PMID Year
1
mip1 containing mutations associated with mitochondrial disease causes mutagenesis and depletion of mtDNA in Saccharomyces cerevisiae. 9 38
20185557 2010
2
Sensory ataxic neuropathy with dysarthria and ophthalmoparesis (SANDO) in late life due to compound heterozygous POLG mutations. 9 38
20513108 2010
3
Localized cerebral energy failure in DNA polymerase gamma-associated encephalopathy syndromes. 9 38
20400524 2010
4
The clinical, histochemical, and molecular spectrum of PEO1 (Twinkle)-linked adPEO. 9 38
20479361 2010
5
Clinical phenotype of autosomal dominant progressive external ophthalmoplegia in a family with a novel mutation in the C10orf2 gene. 9 38
19705478 2010
6
Disruption of mitochondrial DNA replication in Drosophila increases mitochondrial fast axonal transport in vivo. 9 38
19924234 2009
7
Novel POLG1 mutations associated with neuromuscular and liver phenotypes in adults and children. 9 38
19251978 2009
8
Mitochondrial DNA depletion in progressive external ophthalmoplegia caused by POLG1 mutations. 9 38
19566497 2009
9
Twinkle mutations associated with autosomal dominant progressive external ophthalmoplegia lead to impaired helicase function and in vivo mtDNA replication stalling. 9 38
18971204 2009
10
Novel Twinkle (PEO1) gene mutations in mendelian progressive external ophthalmoplegia. 9 38
18575922 2008
11
Two novel POLG1 mutations in a patient with progressive external ophthalmoplegia, levodopa-responsive pseudo-orthostatic tremor and parkinsonism. 9 38
18502641 2008
12
The DNA polymerase gamma Y955C disease variant associated with PEO and parkinsonism mediates the incorporation and translesion synthesis opposite 7,8-dihydro-8-oxo-2'-deoxyguanosine. 9 38
17725985 2007
13
Levodopa response in Parkinsonism with multiple mitochondrial DNA deletions. 9 38
17357142 2007
14
Mutation of the linker region of the polymerase gamma-1 (POLG1) gene associated with progressive external ophthalmoplegia and Parkinsonism. 9 38
17420318 2007
15
Dominant inheritance of premature ovarian failure associated with mutant mitochondrial DNA polymerase gamma. 9 38
16595552 2006
16
Genetic and chemical rescue of the Saccharomyces cerevisiae phenotype induced by mitochondrial DNA polymerase mutations associated with progressive external ophthalmoplegia in humans. 9 38
16940310 2006
17
Mutant POLG2 disrupts DNA polymerase gamma subunits and causes progressive external ophthalmoplegia. 9 38
16685652 2006
18
Mice with neuron-specific accumulation of mitochondrial DNA mutations show mood disorder-like phenotypes. 9 38
16619054 2006
19
Early-onset familial parkinsonism due to POLG mutations. 9 38
16634032 2006
20
Mitochondrial and nuclear DNA defects in Saccharomyces cerevisiae with mutations in DNA polymerase gamma associated with progressive external ophthalmoplegia. 9 38
16368709 2006
21
Association of novel POLG mutations and multiple mitochondrial DNA deletions with variable clinical phenotypes in a Spanish population. 9 38
16401742 2006
22
Eliminating the Ant1 isoform produces a mouse with CPEO pathology but normal ocular motility. 9 38
16303948 2005
23
The adenine nucleotide translocase type 1 (ANT1): a new factor in mitochondrial disease. 9 38
16203679 2005
24
Consequences of mutations in human DNA polymerase gamma. 9 38
15913923 2005
25
A novel ANT1 gene mutation with probable germline mosaicism in autosomal dominant progressive external ophthalmoplegia. 9 38
15792871 2005
26
A novel polymerase gamma mutation in a family with ophthalmoplegia, neuropathy, and Parkinsonism. 9 38
15534189 2004
27
POLG mutations in neurodegenerative disorders with ataxia but no muscle involvement. 9 38
15477547 2004
28
Parkinsonism, premature menopause, and mitochondrial DNA polymerase gamma mutations: clinical and molecular genetic study. 9 38
15351195 2004
29
Structure-function defects of human mitochondrial DNA polymerase in autosomal dominant progressive external ophthalmoplegia. 9 38
15258572 2004
30
POLG mutations causing ophthalmoplegia, sensorimotor polyneuropathy, ataxia, and deafness. 9 38
14745080 2004
31
Patient homozygous for a recessive POLG mutation presents with features of MERRF. 9 38
14694057 2003
32
Remarkable infidelity of polymerase gammaA associated with mutations in POLG1 exonuclease domain. 9 38
14557557 2003
33
Clinical and genetic heterogeneity in progressive external ophthalmoplegia due to mutations in polymerase gamma. 9 38
12975295 2003
34
Digenic progressive external ophthalmoplegia in a sporadic patient: recessive mutations in POLG and C10orf2/Twinkle. 9 38
12872260 2003
35
Novel POLG mutations in progressive external ophthalmoplegia mimicking mitochondrial neurogastrointestinal encephalomyopathy. 9 38
12825077 2003
36
Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO). 9 38
12707443 2003
37
Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia. 9 38
12565911 2003
38
Error catastrophe in mutant mitochondria. 9 38
14603013 2002
39
Mutations of mitochondrial DNA polymerase gammaA are a frequent cause of autosomal dominant or recessive progressive external ophthalmoplegia. 9 38
12210792 2002
40
Active site mutation in DNA polymerase gamma associated with progressive external ophthalmoplegia causes error-prone DNA synthesis. 9 38
11897778 2002
41
Antioxidant agents have a different expression pattern in muscle fibers of patients with mitochondrial diseases. 9 38
11907800 2002
42
A novel missense adenine nucleotide translocator-1 gene mutation in a Greek adPEO family. 9 38
11756613 2001
43
Defects of intergenomic communication: autosomal disorders that cause multiple deletions and depletion of mitochondrial DNA. 9 38
11735376 2001
44
Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. 9 38
11431686 2001
45
Flux control of cytochrome c oxidase in human skeletal muscle. 9 38
10869362 2000
46
[Molecular studies in Cuban patients with progressive external ophthalmoplegia]. 9 38
10904941 2000
47
Superoxide dismutases of muscle in mitochondrial encephalomyopathies. 9 38
7565923 1995
48
"All-or-none" cytochrome c oxidase positivity in mitochondria in chronic progressive external ophthalmoplegia: an ultrastructural--cytochemical study. 9 38
8381519 1993
49
Quantitative evaluation of electron transport system proteins in mitochondrial encephalomyopathy. 9 38
8386896 1993
50
Enzyme activity analyses along ragged-red and normal single muscle fibres. 9 38
1330995 1992

Variations for Chronic Progressive External Ophthalmoplegia

ClinVar genetic disease variations for Chronic Progressive External Ophthalmoplegia:

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

Expression for Chronic Progressive External Ophthalmoplegia

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

Pathways for Chronic Progressive External Ophthalmoplegia

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

# Super pathways Score Top Affiliating Genes
1
Show member pathways
11.17 MT-TL2 MT-TK MT-TI MT-TA

GO Terms for Chronic Progressive External Ophthalmoplegia

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 9.43 TWNK SPG7 SLC25A4 POLG2 POLG COX5A
2 mitochondrial nucleoid GO:0042645 8.8 TWNK POLG2 POLG

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

# Name GO ID Score Top Affiliating Genes
1 DNA replication GO:0006260 9.43 TWNK POLG2 POLG
2 cellular response to glucose stimulus GO:0071333 9.4 TWNK POLG
3 DNA biosynthetic process GO:0071897 9.37 POLG2 POLG
4 DNA-dependent DNA replication GO:0006261 9.32 POLG2 POLG
5 mitochondrial genome maintenance GO:0000002 9.16 TYMP SLC25A4
6 mitochondrion organization GO:0007005 9.13 TWNK SPG7 POLG2
7 mitochondrial DNA replication GO:0006264 8.8 TWNK POLG2 POLG

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 POLG2 POLG

Sources for Chronic Progressive External Ophthalmoplegia

3 CDC
7 CNVD
9 Cosmic
10 dbSNP
11 DGIdb
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18 ExPASy
19 FMA
28 GO
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30 HGMD
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33 ICD10
34 ICD10 via Orphanet
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36 IUPHAR
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58 OMIM via Orphanet
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69 SNOMED-CT via HPO
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73 UMLS via Orphanet
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