Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2023:194:9-21.
doi: 10.1016/B978-0-12-821751-1.00018-X.

Progressive external ophthalmoplegia

Michio Hirano  1 , Robert D S Pitceathly  2
Affiliations
Review

Progressive external ophthalmoplegia

Michio Hirano et al. Handb Clin Neurol. 2023.

Abstract

Progressive external ophthalmoplegia (PEO), characterized by ptosis and impaired eye movements, is a clinical syndrome with an expanding number of etiologically distinct subtypes. Advances in molecular genetics have revealed numerous pathogenic causes of PEO, originally heralded in 1988 by the detection of single large-scale deletions of mitochondrial DNA (mtDNA) in skeletal muscle of people with PEO and Kearns-Sayre syndrome. Since then, multiple point variants of mtDNA and nuclear genes have been identified to cause mitochondrial PEO and PEO-plus syndromes, including mitochondrial neurogastrointestinal encephalomyopathy (MNGIE) and sensory ataxic neuropathy dysarthria ophthalmoplegia (SANDO). Intriguingly, many of those nuclear DNA pathogenic variants impair maintenance of the mitochondrial genome causing downstream mtDNA multiple deletions and depletion. In addition, numerous genetic causes of nonmitochondrial PEO have been identified.

Keywords: Kearns–Sayre syndrome; MNGIE; Mitochondria; Mitochondrial DNA; Ophthalmoplegia; SANDO.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests MH is a paid consultant to Modis Therapeutics, a wholly owned subsidiary of Zogenix/UCB, and Entrada Therapeutics. These relationships are de minimus for Columbia University Medical Center. Columbia University has patents for deoxynucleotide and deoxynucleoside therapies for mitochondrial DNA depletion syndrome, which is licensed by Modis Therapeutics; this relationship is monitored by an unconflicted external academic researcher. Received honoraria from the AAN and PlatformQ for speaking activities and research support from Modis Therapeutics and Entrada Therapeutics.

Figures

Fig. 2.1.
Fig. 2.1.
Ophthalmoparesis in a patient with mitochondrial progressive external ophthalmoplegia due to a single mitochondrial DNA large-scale deletion. The patient has severely impaired upgaze and partially impaired lateral gaze most evident on left lateral gaze with sclera visible on abducting left eye. Mild right ptosis is accentuated on right lateral gaze. Blue arrows denote direction of eye movement.
See this image and copyright information in PMC

References

    1. Alston CL, Lowe J, Turnbull DM et al. (2010). A novel mitochondrial tRNAGlu (MTTE) gene mutation causing chronic progressive external ophthalmoplegia at low levels of heteroplasmy in muscle. J Neurol Sci 298: 140–144. 10.1016/j.jns.2010.08.014. - DOI - PubMed
    1. Aure K, Ogier de Baulny H, Laforet P et al. (2007). Chronic progressive ophthalmoplegia with large-scale mtDNA rearrangement: can we predict progression? Brain 130: 1516–1524. 10.1093/brain/awm067. - DOI - PubMed
    1. Bahn RS (2010). Graves’ ophthalmopathy. N Engl J Med 362: 726–738. 10.1056/NEJMra0905750. - DOI - PMC - PubMed
    1. Barca E, Long Y, Cooley V et al. (2020). Mitochondrial diseases in North America: an analysis of the NAMDC Registry. Neurol Genet 6: e402. 10.1212/NXG.0000000000000402. - DOI - PMC - PubMed
    1. Beaumont WM (1890). Notes of a case of progressive nuclear ophthalmoplegia. Brain 13: 386–387.

MeSH terms

Substances

LinkOut - more resources