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Autosomal dominant progressive external ophthalmoplegia

MedGen UID:
1686757
•Concept ID:
C5231255
•
Disease or Syndrome
Synonyms: adPEO; adPEO - autosomal dominant progressive external ophthalmoplegia; autosomal dominant progressive external ophthalmoplegia; PEOA1; progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant 1; progressive external ophthalmoplegia with mitochondrial DNA deletions, autosomal dominant type 1; progressive external ophthalmoplegia, autosomal dominant
SNOMED CT: Autosomal dominant progressive external ophthalmoplegia (827115000); adPEO - autosomal dominant progressive external ophthalmoplegia (827115000)
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
•Concept ID:
C0443147
•
Intellectual Product
Source: Orphanet
A mode of inheritance that is observed for traits related to a gene encoded on one of the autosomes (i.e., the human chromosomes 1-22) in which a trait manifests in heterozygotes. In the context of medical genetics, an autosomal dominant disorder is caused when a single copy of the mutant allele is present. Males and females are affected equally, and can both transmit the disorder with a risk of 50% for each child of inheriting the mutant allele.
Autosomal dominant inheritance (Orphanet)
 
Related gene: POLG
 
Monarch Initiative: MONDO:0008003
Orphanet: ORPHA254892

Definition

A rare genetic neuro-ophthalmological disease with characteristics of progressive weakness of the external eye muscles, resulting in bilateral ptosis and diffuse symmetric ophthalmoparesis. Additional signs may include skeletal muscle weakness, cataracts, hearing loss, sensory axonal neuropathy, ataxia, parkinsonism, cardiomyopathy, hypogonadism and depression. It is usually less severe than autosomal recessive form. [from SNOMEDCT_US]

Term Hierarchy

CClinical test,  RResearch test,  OOMIM,  GGeneReviews,  VClinVar  

Professional guidelines

PubMed

Clinical criteria for diagnosis of Machado-Joseph disease: report of a non-Azorena Portuguese family.
Lima L, Coutinho P
Neurology 1980 Mar;30(3):319-22. doi: 10.1212/wnl.30.3.319. PMID: 7189034

Recent clinical studies

Etiology

TWNK in Parkinson's Disease: A Movement Disorder and Mitochondrial Disease Center Perspective Study.
Percetti M, Franco G, Monfrini E, Caporali L, Minardi R, La Morgia C, Valentino ML, Liguori R, Palmieri I, Ottaviani D, Vizziello M, Ronchi D, Di Berardino F, Cocco A, Macao B, Falkenberg M, Comi GP, Albanese A, Giometto B, Valente EM, Carelli V, Di Fonzo A
Mov Disord 2022 Sep;37(9):1938-1943. Epub 2022 Jul 6 doi: 10.1002/mds.29139. PMID: 35792653Free PMC Article
Molecular and clinical genetics of mitochondrial diseases due to POLG mutations.
Wong LJ, Naviaux RK, Brunetti-Pierri N, Zhang Q, Schmitt ES, Truong C, Milone M, Cohen BH, Wical B, Ganesh J, Basinger AA, Burton BK, Swoboda K, Gilbert DL, Vanderver A, Saneto RP, Maranda B, Arnold G, Abdenur JE, Waters PJ, Copeland WC
Hum Mutat 2008 Sep;29(9):E150-72. doi: 10.1002/humu.20824. PMID: 18546365Free PMC Article
Alteration of nucleotide metabolism: a new mechanism for mitochondrial disorders.
Martí R, Nishigaki Y, Vilá MR, Hirano M
Clin Chem Lab Med 2003 Jul;41(7):845-51. doi: 10.1515/CCLM.2003.128. PMID: 12940507
Multiple mtDNA deletions features in autosomal dominant and recessive diseases suggest distinct pathogeneses.
Carrozzo R, Hirano M, Fromenty B, Casali C, Santorelli FM, Bonilla E, DiMauro S, Schon EA, Miranda AF
Neurology 1998 Jan;50(1):99-106. doi: 10.1212/wnl.50.1.99. PMID: 9443465
Anticipation of autosomal dominant progressive external ophthalmoplegia with hypogonadism.
Melberg A, Arnell H, Dahl N, Stålberg E, Raininko R, Oldfors A, Bakall B, Lundberg PO, Holme E
Muscle Nerve 1996 Dec;19(12):1561-9. doi: 10.1002/(SICI)1097-4598(199612)19:12<1561::AID-MUS5>3.0.CO;2-8. PMID: 8941270

Diagnosis

POLG-related disorders and their neurological manifestations.
Rahman S, Copeland WC
Nat Rev Neurol 2019 Jan;15(1):40-52. doi: 10.1038/s41582-018-0101-0. PMID: 30451971Free PMC Article
Molecular and clinical genetics of mitochondrial diseases due to POLG mutations.
Wong LJ, Naviaux RK, Brunetti-Pierri N, Zhang Q, Schmitt ES, Truong C, Milone M, Cohen BH, Wical B, Ganesh J, Basinger AA, Burton BK, Swoboda K, Gilbert DL, Vanderver A, Saneto RP, Maranda B, Arnold G, Abdenur JE, Waters PJ, Copeland WC
Hum Mutat 2008 Sep;29(9):E150-72. doi: 10.1002/humu.20824. PMID: 18546365Free PMC Article
Mapping of autosomal dominant progressive external ophthalmoplegia to a 7-cM critical region on 10q24.
Li FY, Tariq M, Croxen R, Morten K, Squier W, Newsom-Davis J, Beeson D, Larsson C
Neurology 1999 Oct 12;53(6):1265-71. doi: 10.1212/wnl.53.6.1265. PMID: 10522883
Neuro-ophthalmic genetics.
Kerrison JB, Maumenee IH
Curr Opin Ophthalmol 1997 Dec;8(6):35-40. doi: 10.1097/00055735-199712000-00006. PMID: 10176101
Anticipation of autosomal dominant progressive external ophthalmoplegia with hypogonadism.
Melberg A, Arnell H, Dahl N, Stålberg E, Raininko R, Oldfors A, Bakall B, Lundberg PO, Holme E
Muscle Nerve 1996 Dec;19(12):1561-9. doi: 10.1002/(SICI)1097-4598(199612)19:12<1561::AID-MUS5>3.0.CO;2-8. PMID: 8941270

Therapy

Autosomal dominant progressive external ophthalmoplegia: distribution of multiple mitochondrial DNA deletions.
Moslemi AR, Melberg A, Holme E, Oldfors A
Neurology 1999 Jul 13;53(1):79-84. doi: 10.1212/wnl.53.1.79. PMID: 10408540
Rhabdomyolysis in autosomal dominant progressive external ophthalmoplegia.
Melberg A, Holme E, Oldfors A, Lundberg PO
Neurology 1998 Jan;50(1):299-300. doi: 10.1212/wnl.50.1.299. PMID: 9443501
An autosomal locus predisposing to multiple deletions of mtDNA on chromosome 3p.
Kaukonen JA, Amati P, Suomalainen A, Rötig A, Piscaglia MG, Salvi F, Weissenbach J, Fratta G, Comi G, Peltonen L, Zeviani M
Am J Hum Genet 1996 Apr;58(4):763-9. PMID: 8644740Free PMC Article

Prognosis

Mitochondrial ANT-1 related adPEO leading to cognitive impairment: is there a link?
Simoncini C, Siciliano G, Tognoni G, Mancuso M
Acta Myol 2017 Mar;36(1):25-27. PMID: 28690391Free PMC Article
Molecular and clinical genetics of mitochondrial diseases due to POLG mutations.
Wong LJ, Naviaux RK, Brunetti-Pierri N, Zhang Q, Schmitt ES, Truong C, Milone M, Cohen BH, Wical B, Ganesh J, Basinger AA, Burton BK, Swoboda K, Gilbert DL, Vanderver A, Saneto RP, Maranda B, Arnold G, Abdenur JE, Waters PJ, Copeland WC
Hum Mutat 2008 Sep;29(9):E150-72. doi: 10.1002/humu.20824. PMID: 18546365Free PMC Article
Structure-function defects of the TWINKLE linker region in progressive external ophthalmoplegia.
Korhonen JA, Pande V, Holmlund T, Farge G, Pham XH, Nilsson L, Falkenberg M
J Mol Biol 2008 Mar 28;377(3):691-705. Epub 2008 Jan 26 doi: 10.1016/j.jmb.2008.01.035. PMID: 18279890
Structure-function defects of human mitochondrial DNA polymerase in autosomal dominant progressive external ophthalmoplegia.
Graziewicz MA, Longley MJ, Bienstock RJ, Zeviani M, Copeland WC
Nat Struct Mol Biol 2004 Aug;11(8):770-6. Epub 2004 Jul 18 doi: 10.1038/nsmb805. PMID: 15258572
Two families with autosomal dominant progressive external ophthalmoplegia.
Kiechl S, Horváth R, Luoma P, Kiechl-Kohlendorfer U, Wallacher-Scholz B, Stucka R, Thaler C, Wanschitz J, Suomalainen A, Jaksch M, Willeit J
J Neurol Neurosurg Psychiatry 2004 Aug;75(8):1125-8. doi: 10.1136/jnnp.2003.025890. PMID: 15258213Free PMC Article

Clinical prediction guides

Rod bipolar cell dysfunction in POLG retinopathy.
Sanderson KG, Millar E, Tumber A, Klatt R, Sondheimer N, Vincent A
Doc Ophthalmol 2021 Feb;142(1):111-118. Epub 2020 Jun 21 doi: 10.1007/s10633-020-09777-w. PMID: 32567010
TWINKLE gene mutation: report of a French family with an autosomal dominant progressive external ophthalmoplegia and literature review.
Martin-Negrier ML, Sole G, Jardel C, Vital C, Ferrer X, Vital A
Eur J Neurol 2011 Mar;18(3):436-41. Epub 2010 Sep 29 doi: 10.1111/j.1468-1331.2010.03171.x. PMID: 20880070
Molecular and clinical genetics of mitochondrial diseases due to POLG mutations.
Wong LJ, Naviaux RK, Brunetti-Pierri N, Zhang Q, Schmitt ES, Truong C, Milone M, Cohen BH, Wical B, Ganesh J, Basinger AA, Burton BK, Swoboda K, Gilbert DL, Vanderver A, Saneto RP, Maranda B, Arnold G, Abdenur JE, Waters PJ, Copeland WC
Hum Mutat 2008 Sep;29(9):E150-72. doi: 10.1002/humu.20824. PMID: 18546365Free PMC Article
Mapping of autosomal dominant progressive external ophthalmoplegia to a 7-cM critical region on 10q24.
Li FY, Tariq M, Croxen R, Morten K, Squier W, Newsom-Davis J, Beeson D, Larsson C
Neurology 1999 Oct 12;53(6):1265-71. doi: 10.1212/wnl.53.6.1265. PMID: 10522883
Anticipation of autosomal dominant progressive external ophthalmoplegia with hypogonadism.
Melberg A, Arnell H, Dahl N, Stålberg E, Raininko R, Oldfors A, Bakall B, Lundberg PO, Holme E
Muscle Nerve 1996 Dec;19(12):1561-9. doi: 10.1002/(SICI)1097-4598(199612)19:12<1561::AID-MUS5>3.0.CO;2-8. PMID: 8941270

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