chronic progressive external ophthalmoplegia

Summary

Summary: A mitochondrial myopathy characterized by slowly progressive paralysis of the levator palpebrae, orbicularis oculi, and extraocular muscles. Ragged-red fibers and atrophy are found on muscle biopsy. Familial and sporadic forms may occur. Disease onset is usually in the first or second decade of life, and the illness slowly progresses until usually all ocular motility is lost. (From Adams et al., Principles of Neurology, 6th ed, p1422)

Top Publications

  1. Kaukonen J, Juselius J, Tiranti V, Kyttälä A, Zeviani M, Comi G, et al. Role of adenine nucleotide translocator 1 in mtDNA maintenance. Science. 2000;289:782-5 pubmed
    ..The analogous mutation in yeast caused a respiratory defect. These results indicate that ANT has a role in mtDNA maintenance and that a mitochondrial disease can be caused by a dominant mechanism...
  2. Van Goethem G, Dermaut B, Lofgren A, Martin J, Van Broeckhoven C. Mutation of POLG is associated with progressive external ophthalmoplegia characterized by mtDNA deletions. Nat Genet. 2001;28:211-2 pubmed
    ..We identified three additional POLG missense mutations compatible with recessive PEO In two nuclear families. POLG is the only DNA polymerase responsible for mtDNA replication...
  3. Spelbrink J, Li F, Tiranti V, Nikali K, Yuan Q, Tariq M, et al. Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria. Nat Genet. 2001;28:223-31 pubmed
    ..The mutations cluster in a region of the protein proposed to be involved in subunit interactions. The function of Twinkle is inferred to be critical for lifetime maintenance of human mtDNA integrity...
  4. Napoli L, Bordoni A, Zeviani M, Hadjigeorgiou G, Sciacco M, Tiranti V, et al. A novel missense adenine nucleotide translocator-1 gene mutation in a Greek adPEO family. Neurology. 2001;57:2295-8 pubmed
    ..The resulting leucine to proline substitution likely modifies the secondary structure of the ANT1 protein. ANT1 gene mutations may account for adPEO in families with different ethnic backgrounds...
  5. Lee A, Brazis P. Chronic progressive external ophthalmoplegia. Curr Neurol Neurosci Rep. 2002;2:413-7 pubmed
    b>Chronic progressive external ophthalmoplegia (CPEO) is a descriptive term for a heterogenous group of disorders characterized by chronic, progressive, bilateral, and usually symmetric ocular motility deficit and ptosis...
  6. Carta A, Carelli V, D Adda T, Ross Cisneros F, Sadun A. Human extraocular muscles in mitochondrial diseases: comparing chronic progressive external ophthalmoplegia with Leber's hereditary optic neuropathy. Br J Ophthalmol. 2005;89:825-7 pubmed
    To compare the ultrastructural aspects of human extraocular muscles in two types of mitochondrial disease: chronic progressive external ophthalmoplegia (CPEO) and Leber's hereditary optic neuropathy (LHON).
  7. Bosbach S, Kornblum C, Schroder R, Wagner M. Executive and visuospatial deficits in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome. Brain. 2003;126:1231-40 pubmed
    ..neuropsychological deficits have been reported in mitochondrial cytopathies, patients with chronic progressive external ophthalmoplegia (CPEO) or Kearns-Sayre syndrome (KSS) have not been studied systematically using a ..
  8. Ritchie A, Griffiths P, Chinnery P, Davidson A. Eye movement recordings to investigate a supranuclear component in chronic progressive external ophthalmoplegia: a cross-sectional study. Br J Ophthalmol. 2010;94:1165-8 pubmed publisher
    It has been postulated that eye movement disorders in chronic progressive external ophthalmoplegia (CPEO) have a neurological as well as a myopathic component to them.
  9. Kin T, Sugie K, Hirano M, Goto Y, Nishino I, Ueno S. Humanin expression in skeletal muscles of patients with chronic progressive external ophthalmoplegia. J Hum Genet. 2006;51:555-8 pubmed
    ..peptide against Alzheimer disease-related insults, was expressed in muscles of patients with chronic progressive external ophthalmoplegia (CPEO), a major mitochondrial disease...

More Information

Publications62

  1. Pulkes T, Liolitsa D, Nelson I, Hanna M. Classical mitochondrial phenotypes without mtDNA mutations: the possible role of nuclear genes. Neurology. 2003;61:1144-7 pubmed
    ..Novel somatic mtDNA mutations in two patients with chronic progressive external ophthalmoplegia were identified...
  2. Caballero P, Candela M, Alvarez C, Tejerina A. Chronic progressive external ophthalmoplegia: a report of 6 cases and a review of the literature. Neurologist. 2007;13:33-6 pubmed
    b>Chronic progressive external ophthalmoplegia is a common mitochondrial disease that shares clinical, enzymatic, and genetic features with other mitochondrial disorders...
  3. Rivera H, Blazquez A, Carretero J, Alvarez Cermeño J, Campos Y, Cabello A, et al. Mild ocular myopathy associated with a novel mutation in mitochondrial twinkle helicase. Neuromuscul Disord. 2007;17:677-80 pubmed
    ..1071G>C (p.R357P) mutation in the hot-spot linker region of the twinkle protein...
  4. DeBrosse S, Ubogu E, Yaniglos S, Hassan M, Leigh R. Dynamic properties of eye movements in mitochondrial chronic progressive external ophthalmoplegia. Eye (Lond). 2009;23:382-8 pubmed
    To relate dynamic properties of eye movements to visual disability in a patient with chronic progressive external ophthalmoplegia (CPEO) due to mitochondrial DNA deletion.
  5. Smits B, Hol F, van den Heuvel L, Drost G, Rodenburg R, ter Laak H, et al. Chronic progressive external ophthalmoplegia caused by an m.4267A > G mutation in the mitochondrial tRNAIle. J Neurol. 2007;254:1614-5 pubmed
  6. Korhonen J, Pande V, Holmlund T, Farge G, Pham X, Nilsson L, et al. Structure-function defects of the TWINKLE linker region in progressive external ophthalmoplegia. J Mol Biol. 2008;377:691-705 pubmed publisher
  7. Kornblum C, Zsurka G, Wiesner R, Schroder R, Kunz W. Concerted action of two novel tRNA mtDNA point mutations in chronic progressive external ophthalmoplegia. Biosci Rep. 2008;28:89-96 pubmed publisher
    CPEO (chronic progressive external ophthalmoplegia) is a common mitochondrial disease phenotype in adults which is due to mtDNA (mitochondrial DNA) point mutations in a subset of patients...
  8. Virgilio R, Ronchi D, Hadjigeorgiou G, Bordoni A, Saladino F, Moggio M, et al. Novel Twinkle (PEO1) gene mutations in mendelian progressive external ophthalmoplegia. J Neurol. 2008;255:1384-91 pubmed publisher
    ..7% of probands of this series. Six novel missense mutations contributing to the mutational load of PEO1 gene (p.R334P, p.W315S, p. S426N, p.W474S, p.F478I, p.E479K) were associated with an adult onset PEO phenotype...
  9. Ahn J, Kim N, Choung H, Hwang S, Sung M, Lee M, et al. Frontalis sling operation using silicone rod for the correction of ptosis in chronic progressive external ophthalmoplegia. Br J Ophthalmol. 2008;92:1685-8 pubmed publisher
    The aim of the study was to evaluate the results of the frontalis sling operation using silicone rod for the correction of ptosis in chronic progressive external ophthalmoplegia patients.
  10. Yu Wai Man C, Smith T, Chinnery P, Turnbull D, Griffiths P. Assessment of visual function in chronic progressive external ophthalmoplegia. Eye (Lond). 2006;20:564-8 pubmed
    To assess the visual function of patients with chronic progressive external ophthalmoplegia (CPEO) using the Visual Function Index (VF-14)...
  11. Soejima K, Sakurai H, Nozaki M, Fujiwara O, Masuda M, Yamada H, et al. Surgical treatment of blepharoptosis caused by chronic progressive external ophthalmoplegia. Ann Plast Surg. 2006;56:439-42 pubmed
    b>Chronic progressive external ophthalmoplegia (CPEO) is a neuromyopathic disorder characterized by progressive weakness of the extraocular and levator muscles, which causes blepharoptosis and impairment of ocular motility...
  12. Houshmand M, Panahi M, Hosseini B, Dorraj G, Tabassi A. Investigation on mtDNA deletions and twinkle gene mutation (G1423C) in Iranian patients with chronic progressive external opthalmoplagia. Neurol India. 2006;54:182-5 pubmed
    ..There are also some reports about the relationship between CPEO and the nuclear Twinkle gene which encodes a kind of mitochondrial protein called Twinkle...
  13. Kiechl S, Horvath R, Luoma P, Kiechl Kohlendorfer U, Wallacher Scholz B, Stucka R, et al. Two families with autosomal dominant progressive external ophthalmoplegia. J Neurol Neurosurg Psychiatry. 2004;75:1125-8 pubmed
    ..We report here the clinical and genetic features of two new families with autosomal dominant progressive external ophthalmoplegia (adPEO)...
  14. Jimenez Caballero P, Servia M, Cabeza C, Marsal Alonso C, Alvarez Tejerina A. [Chronic progressive external ophthalmoplegia: clinical and electromyographic manifestations in a series of cases]. Rev Neurol. 2006;43:724-8 pubmed
    b>Chronic progressive external ophthalmoplegia (CPEO) is a common mitochondrial disease. The different conditions in this group of diseases overlap clinically, enzymatically and genetically. There is no effective treatment...
  15. Deschauer M, Kiefer R, Blakely E, He L, Zierz S, Turnbull D, et al. A novel Twinkle gene mutation in autosomal dominant progressive external ophthalmoplegia. Neuromuscul Disord. 2003;13:568-72 pubmed
  16. Agostino A, Valletta L, Chinnery P, Ferrari G, Carrara F, Taylor R, et al. Mutations of ANT1, Twinkle, and POLG1 in sporadic progressive external ophthalmoplegia (PEO). Neurology. 2003;60:1354-6 pubmed
    ..Irrespective of the inheritance mode, screening of these genes should be performed in all patients with progressive external ophthalmoplegia with multiple mtDNA deletions...
  17. Van Goethem G, Martin J, Dermaut B, Lofgren A, Wibail A, Ververken D, et al. Recessive POLG mutations presenting with sensory and ataxic neuropathy in compound heterozygote patients with progressive external ophthalmoplegia. Neuromuscul Disord. 2003;13:133-42 pubmed
    ..6% in the Belgian population...
  18. Matsushima Y, Kaguni L. Differential phenotypes of active site and human autosomal dominant progressive external ophthalmoplegia mutations in Drosophila mitochondrial DNA helicase expressed in Schneider cells. J Biol Chem. 2007;282:9436-44 pubmed
    ..Our dominant negative analysis of d-mtDNA helicase in cultured cells provides a tractable model for understanding human autosomal dominant progressive external ophthalmoplegia mutations...
  19. Omar A, Johnson L. Tetracycline delays ocular motility decline in chronic progressive external ophthalmoplegia. Neurology. 2007;68:1159-60 pubmed
  20. Lewis S, Hutchison W, Thyagarajan D, Dahl H. Clinical and molecular features of adPEO due to mutations in the Twinkle gene. J Neurol Sci. 2002;201:39-44 pubmed
    ..Thus, Twinkle appears to be the most common gene associated with adPEO in Australian families...
  21. Berardo A, Coku J, Kurt B, DiMauro S, Hirano M. A novel mutation in the tRNAIle gene (MTTI) affecting the variable loop in a patient with chronic progressive external ophthalmoplegia (CPEO). Neuromuscul Disord. 2010;20:204-6 pubmed publisher
    We describe a 62-year-old woman with chronic progressive external ophthalmoplegia (CPEO), multiple lipomas, diabetes mellitus, and a novel mitochondrial DNA (mtDNA) mutation at nucleotide 4302 (4302A>G) of the tRNA(Ile) gene (MTTI)...
  22. Ortube M, Bhola R, Demer J. Orbital magnetic resonance imaging of extraocular muscles in chronic progressive external ophthalmoplegia: specific diagnostic findings. J AAPOS. 2006;10:414-8 pubmed
    b>Chronic progressive external ophthalmoplegia (CPEO) is characterized by slowly progressive bilateral ophthalmoplegia and blepharoptosis. Molecular diagnosis is problematic because sporadic mitochondrial DNA deletions can be causative...
  23. Longley M, Clark S, Yu Wai Man C, Hudson G, Durham S, Taylor R, et al. Mutant POLG2 disrupts DNA polymerase gamma subunits and causes progressive external ophthalmoplegia. Am J Hum Genet. 2006;78:1026-34 pubmed
    ..The progressive accumulation of mtDNA deletions causes COX deficiency in muscle fibers and results in the clinical phenotype...
  24. Tinley C, Dawson E, Lee J. The management of strabismus in patients with chronic progressive external ophthalmoplegia. Strabismus. 2010;18:41-7 pubmed publisher
    To describe the clinical profiles and results of surgical and non-surgical interventions in a large cohort of patients with strabismus associated with chronic progressive external ophthalmoplegia (CPEO).
  25. Baloh R, Salavaggione E, Milbrandt J, Pestronk A. Familial parkinsonism and ophthalmoplegia from a mutation in the mitochondrial DNA helicase twinkle. Arch Neurol. 2007;64:998-1000 pubmed
    ..To describe the clinical phenotype and genetic basis of a family with autosomal dominant progressive external ophthalmoplegia and parkinsonism from a Twinkle mutation...
  26. Bau V, Zierz S. Update on chronic progressive external ophthalmoplegia. Strabismus. 2005;13:133-42 pubmed
    ..The efficacy of pharmacological therapies (e.g., coenzyme Q) has not been established so far. Symptomatic ophthalmological treatment includes ptosis and strabismus surgery. Early cardiac pacemaker implantation may be life-saving...
  27. Taanman J, Burton M, Marusich M, Kennaway N, Capaldi R. Subunit specific monoclonal antibodies show different steady-state levels of various cytochrome-c oxidase subunits in chronic progressive external ophthalmoplegia. Biochim Biophys Acta. 1996;1315:199-207 pubmed
    ..In skeletal muscle sections of a patient with chronic progressive external ophthalmoplegia known to harbor the 'common deletion' in a subpopulation of her mitochondrial DNA, most ..
  28. Schaefer A, Blakely E, Griffiths P, Turnbull D, Taylor R. Ophthalmoplegia due to mitochondrial DNA disease: the need for genetic diagnosis. Muscle Nerve. 2005;32:104-7 pubmed
    We describe a patient with chronic progressive external ophthalmoplegia (CPEO) who underwent muscle biopsy for suspected mitochondrial disease...
  29. Richardson C, Smith T, Schaefer A, Turnbull D, Griffiths P. Ocular motility findings in chronic progressive external ophthalmoplegia. Eye (Lond). 2005;19:258-63 pubmed
    ..To characterise the ocular motility features of chronic progressive external opthalmoplegia by quantitative and semiquantitative means. To assess the prevalence of diplopia and the binocular adaptations to nonaligned visual axes...
  30. Salvan A, Vion Dury J, Confort Gouny S, Sangla I, Pouget J, Cozzone P. Brain metabolic profiles obtained by proton MRS in two forms of mitochondriopathies: Leber's hereditary optic neuropathy and chronic progressive external ophthalmoplegia. Eur Neurol. 1998;40:46-9 pubmed
    ..involvement: 2 patients with Leber's hereditary optic neuropathy (LHON) and 4 patients with chronic progressive external ophthalmoplegia (CPEO). Patients with LHON displayed normal spectra...
  31. Spagnolo M, Tomelleri G, Vattemi G, Filosto M, Rizzuto N, Tonin P. A new mutation in the mitochondrial tRNA(Ala) gene in a patient with ophthalmoplegia and dysphagia. Neuromuscul Disord. 2001;11:481-4 pubmed
    ..gene, a T-->C transition at nucleotide position 5628, in a 62-year-old woman with late onset chronic progressive external ophthalmoplegia, dysphagia and mild proximal myopathy...
  32. Gutowski N, Bosley T, Engle E. 110th ENMC International Workshop: the congenital cranial dysinnervation disorders (CCDDs). Naarden, The Netherlands, 25-27 October, 2002. Neuromuscul Disord. 2003;13:573-8 pubmed
  33. Cardaioli E, Da Pozzo P, Malfatti E, Gallus G, Rubegni A, Malandrini A, et al. Chronic progressive external ophthalmoplegia: a new heteroplasmic tRNA(Leu(CUN)) mutation of mitochondrial DNA. J Neurol Sci. 2008;272:106-9 pubmed publisher
    We sequenced all genes of mitochondrial tRNAs of a patient with chronic progressive external ophthalmoplegia with 5% ragged red fibres and 15% COX-negative fibres but without macrorearrangements of mitochondrial DNA (mtDNA)...
  34. Ascaso F, Torres M, Bergua J, Alvarez R, Cristobal J. Progressive external ophthalmoplegia: a paraneoplastic manifestation of lymphoma. Eur J Ophthalmol. 2002;12:315-8 pubmed
    ..Paraneoplastic neurological syndromes are well-known sequelae of some malignancies. To our knowledge, a syndrome mimicking progressive external ophthalmoplegia had never been reported preceding the diagnosis of a lymphoma...
  35. Pranzatelli M, Tate E. Chloral hydrate for progressive myoclonus epilepsy: a new look at an old drug. Pediatr Neurol. 2001;25:385-9 pubmed
    ..Recent evidence of interactions with various excitatory and inhibitory amino acid neurotransmitter-operated ion channels as a mechanism of action may provide insight into altered neurotransmission in progressive myoclonus epilepsy...
  36. Nonaka I. Mitochondrial diseases. Curr Opin Neurol Neurosurg. 1992;5:622-32 pubmed
    ..mutant mtDNA exceeds a certain threshold, which differs from mutation to mutation: 60 to 70% in chronic progressive external ophthalmoplegia (CPEO) and probably 95% in the syndromes of mitochondrial encephalopathy, myopathy, lactic ..
  37. Molnar M, Neudecker S, Schroder J. Increase of mitochondria in vasa nervorum of cases with mitochondrial myopathy, Kearns-Sayre syndrome, progressive external ophthalmoplegia and MELAS. Neuropathol Appl Neurobiol. 1995;21:432-9 pubmed
  38. Lopez Gallardo E, López Pérez M, Montoya J, Ruiz Pesini E. CPEO and KSS differ in the percentage and location of the mtDNA deletion. Mitochondrion. 2009;9:314-7 pubmed publisher
    ..Thus, the moment when the deletion is produced probably not only determines the affected tissues and the phenotype, but also the percentage and location of the deletion...
  39. Salvi S, Currie Z. Frontalis suspension sling using palmaris longus tendon in chronic progressive external ophthalmoplegia. Ophthalmic Plast Reconstr Surg. 2009;25:140-1 pubmed publisher
    A 26-year-old woman referred with bilateral ptosis was diagnosed to have underlying chronic progressive external ophthalmoplegia. The authors report satisfactory result at 18-month follow-up with palmaris longus tendon used as an ..
  40. Barbiroli B, Iotti S, Lodi R. Aspects of human bioenergetics as studied in vivo by magnetic resonance spectroscopy. Biochimie. 1998;80:847-53 pubmed
  41. Cardaioli E, Da Pozzo P, Gallus G, Malandrini A, Gambelli S, Gaudiano C, et al. A novel heteroplasmic tRNA(Ser(UCN)) mtDNA point mutation associated with progressive external ophthalmoplegia and hearing loss. Neuromuscul Disord. 2007;17:681-3 pubmed
    ..Several point mutations on mitochondrial tRNA genes have been reported in PEO patients without large-scale rearrangements of mtDNA but no point mutations have hitherto been found in the gene coding for tRNA(Ser(UCN))...
  42. Graziewicz M, Longley M, Bienstock R, Zeviani M, Copeland W. Structure-function defects of human mitochondrial DNA polymerase in autosomal dominant progressive external ophthalmoplegia. Nat Struct Mol Biol. 2004;11:770-6 pubmed
    ..The reduced selectivity and catalytic efficiency of the autosomal dominant PEO mutants predict in vivo dysfunction, and the extent of biochemical defects correlates with the clinical severity of the disease...
  43. Melberg A, Nennesmo I, Moslemi A, Kollberg G, Luoma P, Suomalainen A, et al. Alzheimer pathology associated with POLG1 mutation, multiple mtDNA deletions, and APOE4/4: premature ageing or just coincidence?. Acta Neuropathol. 2005;110:315-6 pubmed
  44. Honjo K, Mimori Y, Morino H, Katayama S, Nakamura S. [A case of late onset mitochondrial neuromyopathy]. Nihon Ronen Igakkai Zasshi. 2002;39:318-21 pubmed
    ..Although her mtDNA abnormality was compatible with chronic progressive external ophthalmoplegia (CPEO), we speculate that the aging process may be contributed to the mtDNA abnormality, which ..
  45. Andrews R, Griffiths P, Chinnery P, Turnbull D. Evaluation of bupivacaine-induced muscle regeneration in the treatment of ptosis in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome. Eye (Lond). 1999;13 ( Pt 6):769-72 pubmed
    ..This study was undertaken to assess the potential of this approach in restoring levator muscle function in patients with mitochondrial disease and ptosis...
  46. Kaukonen J, Zeviani M, Comi G, Piscaglia M, Peltonen L, Suomalainen A. A third locus predisposing to multiple deletions of mtDNA in autosomal dominant progressive external ophthalmoplegia. Am J Hum Genet. 1999;65:256-61 pubmed
  47. Wang Z, Yuan Y, Gao F, Qi Y, Shen D, Chen Q. [Mitochondrial DNA mutations in patients with chronic progressive external ophthalmoplegia and Kearns-Sayre syndrome]. Zhonghua Yi Xue Yi Chuan Xue Za Zhi. 2003;20:273-8 pubmed
    Kearns-Sayre syndrome (KSS) and chronic progressive external ophthalmoplegia (CPEO) belong to neurological diseases caused by a defect in the energy-producing system of mitochondria, and are known to be associated with a deletion in the ..
  48. Hoopes L. Error catastrophe in mutant mitochondria. Sci Aging Knowledge Environ. 2002;2002:vp6 pubmed
    ..The affected mitochondria appear to exhibit an age-dependent error catastrophe. It is possible that other genetic diseases might result in error catastrophes in mitochondria as well...
  49. Sotiriou E, Coku J, Tanji K, Huang H, Hirano M, DiMauro S. The m.3244G>A mutation in mtDNA is another cause of progressive external ophthalmoplegia. Neuromuscul Disord. 2009;19:297-9 pubmed publisher
    We sequenced all mitochondrial tRNA genes in a 61-year-old man with chronic progressive external ophthalmoplegia and mitochondrial myopathy but without mtDNA rearrangements, and identified a heteroplasmic m...
  50. Versino M, Colnaghi S, Todeschini A, Candeloro E, Ravaglia S, Moglia A, et al. Ocular neuromyotonia with both tonic and paroxysmal components due to vascular compression. J Neurol. 2005;252:227-9 pubmed
  51. Kim S, Chi J, Reith A, Kadenbach B. Quantitative analysis of mitochondrial DNA deletion in paraffin embedded muscle tissues from patients with KSS and CPEO. Biochim Biophys Acta. 1997;1360:193-5 pubmed
    ..skeletal muscle tissues from two patients with Kearns Sayre syndrome (KSS) and one with chronic progressive external ophthalmoplegia (CPEO)...
  52. Horvath R, Hudson G, Ferrari G, Fütterer N, Ahola S, Lamantea E, et al. Phenotypic spectrum associated with mutations of the mitochondrial polymerase gamma gene. Brain. 2006;129:1674-84 pubmed
    ..1399G-->A (A467T) is common in children, but complete POLG1 sequencing is required to identify multiple mutations that can have complex implications for genetic counselling...
  53. Hisama F, Mancuso M, Filosto M, DiMauro S. Progressive external ophthalmoplegia: a new family with tremor and peripheral neuropathy. Am J Med Genet A. 2005;135:217-9 pubmed