Chronic Progressive External Ophthalmoplegia

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

Background

Chronic progressive external ophthalmoplegia (CPEO) is a disorder characterized by slowly progressive paralysis of the extraocular muscles. Patients usually experience bilateral, symmetrical, progressive ptosis, followed by ophthalmoparesis months to years later. Ciliary and iris muscles are not involved.

Mitochondrial disorders result in an array of clinical manifestations. These can affect unique anatomic structures such as the eye (Leber hereditary optic neuropathy) or multiple systems, resulting in a variegated presentation (ataxia neuropathy syndrome [ANS], of which sensory, ataxia, neuropathy, dysarthria, and ophthalmoplegia [SANDO] is one). [1] . Kearns-Sayre syndrome (KSS) affects the heart and eyes. Pearson syndrome can manifest as pancytopenia, pancreatic problems, and renal tubular maladies. [1]

CPEO is the most frequent manifestation of mitochondrial myopathies. [2, 3] CPEO in association with mutations in mitochondrial DNA (mtDNA) may occur in the absence of any other clinical sign, but it is usually associated with skeletal muscle weakness. However, individuals with a similar clinical presentation may have various mitochondrial defects . [1]

Kearns-Sayre syndrome (KSS) is a related mitochondrial myopathy that demonstrates the following: CPEO, onset before age 20 years, and pigmentary retinopathy. KSS also has at least one of the following: cardiac conduction defects, cerebrospinal fluid (CSF), protein level greater than 100 mg/dL, and a cerebellar syndrome. Other abnormalities in KSS can include mental retardation, Babinski sign, hearing loss, seizures, short stature, delayed puberty, and various endocrine disorders, [4] such as diabetes mellitus, hypoparathyroidism, and hearing loss. [1]

CPEO can also be a sign in the following disorders: oculopharyngeal dystrophy, myasthenia gravis, and Graves disease.

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Pathophysiology

Mitochondrial DNA encodes for essential components of the respiratory chain. Deletions of various lengths of mtDNA results in defective mitochondrial function, particularly in highly oxidative tissues (eg, muscle, brain, heart). Extraocular muscles are affected preferentially because their fraction of mitochondrial volume is several times greater than that of other skeletal muscle. [5, 6]

Impaired protein synthesis in these mitochondria accounts for the histological hallmark of the mitochondrial myopathies. When muscle fibers are stained with Gomori trichrome stain, an abnormal accumulation of enlarged mitochondria is seen beneath the sarcolemma. These fibers are called ragged red fibers due to their unusual appearance and dark red color.

A variable proportion of deleted mtDNA has been found to be present in different tissues from the same patient. The balance of oxidative demands of a given tissue and the proportion of deleted mtDNA it contains will ultimately determine whether the tissue is affected clinically. [7]

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Epidemiology

Frequency

Worldwide

Worldwide, the prevalence of mitochondrial disease is 11.5 cases per 100,000 population. [1]

United States

CPEO is rare. Approximately 1000-4000 children are born with mitochondrial disease annually in the United States. [8]

Sex

In KSS, boys and girls are affected equally.

Age

In KSS, onset of CPEO is before age 20 years.

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