Chronic Progressive External Ophthalmoplegia (CPEO) Clinical Presentation

Updated: Oct 01, 2018
  • Author: Michael Mercandetti, MD, MBA, FACS; Chief Editor: Hampton Roy, Sr, MD  more...
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Presentation

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. [15] 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.

However, many atypical presentations of CPEO have been reported. [16, 17, 18]

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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 entire mitochondrial DNA (mtDNA) from a 54-year-old man with chronic progressive ophthalmoplegia and hyperCKemia has been sequenced. [19]

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Complications

Complications can include cardiac problems and esophageal dysfunction.

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