Chronic progressive external ophthalmoplegia

Chronic progressive external ophthalmoplegia (CPEO) can be inherited, or it can occur sporadically (due to a new mutation in an individual with no history of the condition in the family).

CPEO is considered a "mitochondrial disorder." This is because all the genetic mutations that can cause CPEO ultimately result in dysfunction of the mitochondria, which are structures in our cells that produce energy required for normal cell function. While most of our DNA is located in the cell's center (nuclear DNA), some of our DNA is located within the mitochondria (mitochondrial DNA). CPEO can be caused by mutations in any of several genes, which may be located in mitochondrial DNA or nuclear DNA. It has different inheritance patterns depending on the gene involved in the affected individual.

Unlike nuclear DNA which is inherited from both the mother and the father, mitochondrial DNA is inherited from only the mother. In CPEO, the affected mitochondria (i.e., the ones carrying the mutations) are found only in the skeletal muscle cells. These mitochondrial DNA mutations are almost always sporadic (occurring by chance for the first time in the affected individual). Nuclear gene mutations that cause CPEO may be inherited in an autosomal recessive or autosomal dominant manner, depending on the gene involved. The risk for other family members to be affected depends on the genetic cause and the inheritance pattern in the family.

Chronic progressive external ophthalmoplegia (CPEO) can be found in other forms of mitochondrial myopathies. In particular, CPEO is found in a related mitochondrial myopathy called Kearns-Sayre Syndrome. In addition, some people with CPEO have some symptoms of Kearns- Sayre syndrome, such as ataxia, dementia, or sensorineural hearing loss, in addition to the characteristic symptoms of CPEO. In these cases the people may be said to have CPEO-plus.

CPEO may also be found in other disorder such as oculopharyngeal muscular dystrophy, and myasthenia gravis.

Mitochondrial myopathies in general can cause weakness in muscles of the face and neck. In our search of the medical literature we were able to find case reports describing this symptom in people with chronic progressive external ophthalmoplegia specifically.

Chronic progressive external ophthalmoplegia (CPEO) can be an isolated condition, or it can occur as part of other underlying conditions, such as ataxia neuropathy spectrum and Kearns-Sayre syndrome. These conditions may involve not only CPEO, but various additional features that are not shared by most individuals with CPEO in isolation. Individuals with isolated CPEO generally have a normal life expectancy. While symptoms tend to worsen over time, the specific symptoms and their severity can vary greatly from person to person. Therefore, when symptoms first appear, the course of the condition is very difficult to predict.

For individuals with additional symptoms or another underlying condition associated with CPEO, the prognosis depends on the specific signs and symptoms present and/or the outlook associated with the underlying condition in the affected individual. For this reason, obtaining an accurate diagnosis is very important.

Ptosis caused by chronic progressive external ophthalmoplegia (CPEO) can be corrected by surgery, or by using glasses that have a “ptosis crutch” to lift the upper eyelids. Strabismus surgery can be helpful in carefully selected patients if diplopia (double vision) occurs.

Some individuals with a deficiency of coenzyme Q10 have CPEO as an associated abnormality. Coenzyme Q10 is important for normal mitochondrial function. In individuals with this deficiency, supplemental coenzyme Q10 has been found to improve general neurologic function and exercise tolerance. However, coenzyme Q10 has not been shown to improve the ophthalmoplegia or ptosis in people who have isolated CPEO.

GeneReviews provides a current, expert-authored, peer-reviewed, full-text article on mitochondrial disorders, including CPEO. GeneReview articles describe the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.