Mitochondrial DNA-related progressive external ophthalmoplegia

Mitochondrial DNA-related progressive external ophthalmoplegia (mtDNA-related PEO), also known as maternally inherited progressive external ophthalmoplegia, is a rare mitochondrial disorder characterized by the slow, progressive paralysis of the extraocular muscles. The condition is caused by point mutations or single large-scale deletions in mitochondrial DNA (mtDNA). The hallmark features include bilateral ptosis (drooping of the eyelids) and progressive limitation of eye movements (ophthalmoplegia), which typically develop in adulthood. Because the eyes are affected symmetrically, patients rarely experience double vision (diplopia). Over time, additional features may develop, reflecting the systemic nature of mitochondrial dysfunction. Beyond the eyes, the disease can affect skeletal muscles, leading to generalized muscle weakness and exercise intolerance. Some patients develop additional features such as dysphagia (difficulty swallowing), sensorineural hearing loss, peripheral neuropathy, ataxia, depression, and cardiac conduction defects. Skeletal muscle biopsy typically reveals ragged red fibers and cytochrome c oxidase (COX)-negative fibers, which are characteristic of mitochondrial myopathies. The severity and range of symptoms can vary considerably, even among members of the same family carrying the same mtDNA mutation. There is currently no cure for mtDNA-related progressive external ophthalmoplegia. Management is supportive and symptomatic. Ptosis may be addressed with surgical correction (frontalis sling procedures) or ptosis crutches attached to eyeglasses. Physical therapy and aerobic exercise programs may help maintain muscle function. Cardiac monitoring is recommended due to the risk of conduction abnormalities. Coenzyme Q10 and other mitochondrial supplements are sometimes used, though evidence for their efficacy remains limited. Genetic counseling is important, particularly regarding the maternal inheritance pattern and the challenges of predicting disease severity in offspring.

Common questions about Mitochondrial DNA-related progressive external ophthalmoplegia