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Chronic Progressive External Ophthalmoplegia Clinical Presentation

  • Author: Michael Mercandetti, MD, MBA, FACS; Chief Editor: Hampton Roy, Sr, MD  more...
 
Updated: Jun 20, 2016
 

History

Chronic progressive external ophthalmoplegia (CPEO) tends to begin in young adulthood. Ptosis usually is the first clinical sign, and ophthalmoplegia may not become apparent for months to years. The ptosis is usually bilateral and symmetrical. As the ptosis progresses, the patient may use the frontalis muscle to elevate the eyelids, adopt a chin-up head position, and eventually resort to manual elevation of the eyelids, as ptosis often becomes complete.[9] Cases have been documented of patients who develop ophthalmoplegia but not ptosis. Unilateral or asymmetric ptosis may develop.

Because of the symmetric nature of this disorder, patients often do not complain of diplopia. They may be unaware of their decreased motility until it becomes severe. In many cases, downward gaze is preserved to a greater extent than up-gaze or horizontal movement. The course of CPEO is characterized by constant progression without periods of remission or exacerbation. Patients also may complain of dryness of the eyes due to exposure keratopathy.

In contrast to myasthenia gravis, patients with CPEO usually report little to no variability in their ptosis.

In KSS, children are usually healthy at birth. Boys and girls are affected equally. CPEO and pigmentary retinopathy appear before age 20 years. The retinal pigment undergoes atrophy, usually in a salt-and-pepper pattern without the bony spicule formation typical of retinitis pigmentosa. Ophthalmoplegia generally precedes the development of cardiac conduction disturbances. Sudden death may occur from these disturbances, and patients should have regular cardiac exams, regardless of age. Patients also may have the following: intraventricular septal hypertrophy, mitral valve prolapse, and left ventricular dysfunction.

Weakness of somatic muscles is often noted with progressive facial muscle weakness and neck and shoulder weakness. Extremities tend to be involved to a lesser degree.

Neurologic abnormalities may include the following:

  • Cerebellar ataxia
  • Pendular nystagmus
  • Vestibular dysfunction and/or hearing loss

Endocrine dysfunction is common and may include the following:

  • Short stature
  • Hypoparathyroidism
  • Diabetes
  • Gonadal dysfunction
  • Hyperaldosteronism
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Physical

A complete ophthalmologic examination should be performed, to include the following:

  • Dilated retinal examination
  • Cranial nerve testing
  • Forced duction testing

In KSS, the salt-and-pepper retinopathy usually occurs initially in the posterior fundus. Pallor of the optic disc, attenuation of retinal vessels, visual field defects, and posterior cataract formation common to retinitis pigmentosa rarely, if ever, occur.

CPEO must be differentiated from myasthenia gravis, Graves disease, and oculopharyngeal dystrophy. The table presented below may also be helpful for categorizing physical findings.

Note the image below.

This table outlines the differential diagnoses of This table outlines the differential diagnoses of chronic progressive external ophthalmoplegia.
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Causes

The mitochondrial myopathies and encephalopathies are a complex group of disorders arising from mtDNA mutations. Little correlation exists between the size and the location of the deletion and the clinical phenotype (ie, CPEO vs KSS). Mutations usually occur sporadically, but they also can be inherited as a point mutation of maternal mitochondrial tRNA or as autosomal dominant and autosomal recessive deletions of mtDNA.

The authors have sequenced the entire mitochondrial DNA (mtDNA) from a 54-year-old man with chronic progressive ophthalmoplegia and hyperCKemia.[10]

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Contributor Information and Disclosures
Author

Michael Mercandetti, MD, MBA, FACS Private Practice

Michael Mercandetti, MD, MBA, FACS is a member of the following medical societies: American Academy of Facial Plastic and Reconstructive Surgery, Sarasota County Medical Society, American Academy of Ophthalmology, American College of Surgeons, American Society for Laser Medicine and Surgery, American Society of Ophthalmic Plastic and Reconstructive Surgery, Association of Military Surgeons of the US

Disclosure: Nothing to disclose.

Coauthor(s)

Adam J Cohen, MD Assistant Professor of Ophthalmology, Section Director of Oculoplastic and Reconstructive Surgery, Rush Medical College of Rush University Medical Center

Adam J Cohen, MD is a member of the following medical societies: American Academy of Ophthalmology, American Society of Ophthalmic Plastic and Reconstructive Surgery, American College of Surgeons

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: BioD, Poferious<br/>Serve(d) as a speaker or a member of a speakers bureau for: IOP<br/>Received income in an amount equal to or greater than $250 from: IOP for speaking.

Specialty Editor Board

Simon K Law, MD, PharmD Clinical Professor of Health Sciences, Department of Ophthalmology, Jules Stein Eye Institute, University of California, Los Angeles, David Geffen School of Medicine

Simon K Law, MD, PharmD is a member of the following medical societies: American Academy of Ophthalmology, Association for Research in Vision and Ophthalmology, American Glaucoma Society

Disclosure: Nothing to disclose.

Chief Editor

Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Additional Contributors

Edsel Ing, MD, FRCSC Associate Professor, Department of Ophthalmology and Vision Sciences, University of Toronto Faculty of Medicine; Consulting Staff, Hospital for Sick Children and Sunnybrook Hospital

Edsel Ing, MD, FRCSC is a member of the following medical societies: American Academy of Ophthalmology, American Association for Pediatric Ophthalmology and Strabismus, American Society of Ophthalmic Plastic and Reconstructive Surgery, Royal College of Physicians and Surgeons of Canada, Canadian Ophthalmological Society, North American Neuro-Ophthalmology Society, Canadian Society of Oculoplastic Surgery, European Society of Ophthalmic Plastic and Reconstructive Surgery, Canadian Medical Association, Ontario Medical Association, Statistical Society of Canada, Chinese Canadian Medical Society

Disclosure: Nothing to disclose.

Hampton Roy, Sr, MD Associate Clinical Professor, Department of Ophthalmology, University of Arkansas for Medical Sciences

Hampton Roy, Sr, MD is a member of the following medical societies: American Academy of Ophthalmology, American College of Surgeons, Pan-American Association of Ophthalmology

Disclosure: Nothing to disclose.

Acknowledgements

Tracey A Schmucker, MD Ophthalmologist, Private Practice

Disclosure: Nothing to disclose.

Brian R Younge, MD Professor of Ophthalmology, Mayo Clinic School of Medicine

Brian R Younge, MD is a member of the following medical societies: American Medical Association, American Ophthalmological Society, and North American Neuro-Ophthalmology Society

Disclosure: Nothing to disclose.

References
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  6. Ohnuki Y, Takahashi K, Iijima E, Takahashi W, Suzuki S, Ozaki Y, et al. Multiple deletions in mitochondrial DNA in a patient with progressive external ophthalmoplegia, leukoencephalopathy and hypogonadism. Intern Med. 2014. 53 (12):1365-9. [Medline].

  7. Kiyomoto BH, Tengan CH, Moraes CT, et al. Mitochondrial DNA defects in Brazilian patients with chronic progressive external ophthalmoplegia. J Neurol Sci. 1997 Nov 25. 152(2):160-5. [Medline].

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  9. Ahn J, Kim NJ, Choung HK, et al. Frontalis sling operation using silicone rod for the correction of ptosis in chronic progressive external ophthalmoplegia. Br J Ophthalmol. Sept 11,2008.

  10. Souilem S, Chebel S, Mancuso M, et al. A novel mitochondrial tRNA(Ile) point mutation associated with chronic progressive external ophthalmoplegia and hyperCKemia. J Neurol Sci. 2011 Jan 15. 300(1-2):187-90. [Medline].

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  19. Galetta F, Franzoni F, Mancuso M, Orsucci D, Tocchini L, Papi R, et al. Cardiac involvement in chronic progressive external ophthalmoplegia. J Neurol Sci. 2014 Oct 15. 345 (1-2):189-92. [Medline].

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This table outlines the differential diagnoses of chronic progressive external ophthalmoplegia.
 
 
 
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