Difficulty in swallowing.

A type of hearing impairment in one or both ears related to an abnormal functionality of the cochlear nerve.

A loss of global cognitive ability of sufficient amount to interfere with normal social or occupational function. Dementia represents a loss of previously present cognitive abilities, generally in adults, and can affect memory, thinking, language, judgment, and behavior.

Reduction of neurologic reflexes such as the knee-jerk reaction.

An abnormality characterized by disruption of the normal functioning of peripheral axons.

Atrophy of the cortex of the cerebrum.

Breakdown of muscle fibers that leads to the release of muscle fiber contents (myoglobin) into the bloodstream.

A lack of strength of the proximal muscles.

Reduced strength of the musculature of the distal extremities.

The presence of skeletal muscular atrophy (which is also known as amyotrophy).

An abnormal appearance of muscle fibers observed on muscle biopsy. Ragged red fibers can be visualized with Gomori trichrome staining as irregular and intensely red subsarcolemmal zones, whereas the normal myofibrils are green. The margins of affect fibers appear red and ragged. The ragged-red is due to the accumulation of abnormal mitochondria below the plasma membrane of the muscle fiber, leading to the appearance of a red rim and speckled sarcoplasm.

The presence of multiple deletions of mitochondrial DNA (mtDNA).

An abnormally reduced activity of the enzyme cytochrome C oxidase in muscle tissue.

An elevation of the level of the enzyme creatine kinase (also known as creatine phosphokinase (CK; EC 2.7.3.2) in the blood. CK levels can be elevated in a number of clinical disorders such as myocardial infarction, rhabdomyolysis, and muscular dystrophy.

Abnormally increased level of blood lactate (2-hydroxypropanoic acid). Lactate is produced from pyruvate by lactate dehydrogenase during normal metabolism. The terms lactate and lactic acid are often used interchangeably but lactate (the component measured in blood) is strictly a weak base whereas lactic acid is the corresponding acid. Lactic acidosis is often used clinically to describe elevated lactate but should be reserved for cases where there is a corresponding acidosis (pH below 7.35).

Difficulty in speaking due to a physical disorder of the mouth, tongue, throat, or vocal cords. Associated with a known physical or neurological cause.

The upper eyelid margin is positioned 3 mm or more lower than usual and covers the superior portion of the iris (objective); or, the upper lid margin obscures at least part of the pupil (subjective).

Progressive external ophthalmoplegia is a condition characterized by weakness of the eye muscles. The condition typically appears in adults between ages 18 and 40 and slowly worsens over time. The first sign of progressive external ophthalmoplegia is typically drooping eyelids (ptosis), which can affect one or both eyelids. As ptosis worsens, affected individuals may use the forehead muscles to try to lift the eyelids, or they may lift up their chin in order to see. Another characteristic feature of progressive external ophthalmoplegia is weakness or paralysis of the muscles that move the eye (ophthalmoplegia). Affected individuals have to turn their head to see in different directions, especially as the ophthalmoplegia worsens. People with progressive external ophthalmoplegia may also have general weakness of the muscles used for movement (myopathy), particularly those in the neck, arms, or legs. The weakness may be especially noticeable during exercise (exercise intolerance). Muscle weakness may also cause difficulty swallowing (dysphagia).\n\nWhen the muscle cells of affected individuals are stained and viewed under a microscope, these cells usually appear abnormal. These abnormal muscle cells contain an excess of cell structures called mitochondria and are known as ragged-red fibers.\n\nAlthough muscle weakness is the primary symptom of progressive external ophthalmoplegia, this condition can be accompanied by other signs and symptoms. In these instances, the condition is referred to as progressive external ophthalmoplegia plus (PEO+). Additional signs and symptoms can include hearing loss caused by nerve damage in the inner ear (sensorineural hearing loss), weakness and loss of sensation in the limbs due to nerve damage (neuropathy), impaired muscle coordination (ataxia), a pattern of movement abnormalities known as parkinsonism, and depression.\n\nProgressive external ophthalmoplegia is part of a spectrum of disorders with overlapping signs and symptoms. Similar disorders include ataxia neuropathy spectrum and Kearns-Sayre syndrome. Like progressive external ophthalmoplegia, the other conditions in this spectrum can involve weakness of the eye muscles. However, these conditions have many additional features not shared by most people with progressive external ophthalmoplegia.