The cardinal symptom of chronic progressive external ophthalmoplegia (CPEO) is conjugate horizontal and vertical gaze palsy (symmetrical impairment of external eye muscles).

Initially, horizontal as well as vertical saccades are very slow, and the saccade latency is prolonged. Patients may complain of diplopia or oscillopsia when the eye muscles are asymmetrically affected and the eye axes are not aligned.
The disease progresses, as the name suggests, to complete ophthalmoplegia; ‘staring eyes’ with no possible eye movement are typical. The gaze palsy is associated with a bilateral, usually symmetrical ptosis.

Gains of VOR and smooth pursuit are also reduced. CPEO is often isolated and represents the mild variant of complex mitochondrial disorders. When other symptoms are also present (eg, weakness of the oropharyngeal muscles with related speech and swallowing difficulties), it is referred to as CPEO plus syndrome. 

Causes
Up to 60% cases of mitochondrial CPEO are due to mitochondrial DNA (mtDNA) deletions (ranging from 1.3 to 1.9 kb). Other cases however are due to nuclear DNA (nDNA)-related defects of mtDNA maintenance (e.g., POLG1, ANT, C10orf2/twinkle or POLG2). Sporadic cases of CPEO suggest de novo mutations in mtDNA while autosomal dominant or recessive inheritance patterns point to nDNA mutations.

1. Kearn–Sayre syndrome, a multisystem disorder with central nervous system involvement caused by a large-scale mtDNA deletion. Onset is usally before 20 years of age, cerebellar ataxia, pigmentary retinopathy (usually rod-cone dystrophy) with a “salt-and-pepper” or “moth-eaten” appearance. Cardiac conduction block (potentially a cause of death in young adulthood) and elevated cerebrospinal fluid protein level are typical for this syndrome. Patients experience a progressive loss of peripheral and night vision.
   Other neurological problems may include proximal myopathy, exercise intolerance, oropharyngeal and esophageal dysfunction, sensorineural hearing loss, and cognitive impairment.
2. MELAS syndrome (mitochondrial myopathy, encephalopathy, lactate acidosis and stroke-like episodes)
3. MERRF syndrome (myoclonic epilepsy with ragged red fibers)
4. ARCO syndrome (autosomal recessive cardiomyopathy, ophthalmoplegia)¹. 
5. Oculopharyngeal Musculodystrophy. This is an autosomal dominant disorder with pathologic GCG trinucleotide repeat expansions in the polyalanine-binding protein 1 (PABP1) gene. The mutated PAPB1 proteins aggregate as intranuclear tubular filaments and can cause failure of muscle regeneration.  OPMD is not a mitochondrial myopathy. Symptoms present in the fifth decade of life and in addition to CPEO, include bulbar symptoms such as dysphagia (due to pharyngeal muscle weakness), weakness of the orbicularis oculi muscles, and proximal limb weakness.
6. Myotonic Dystrophy. This well known neurological disorder has congenital, childhood, and classical forms, with onset at birth, childhood, and adulthood, respectively.  This syndrome has a multitude of both ocular and systemic findings. Ocular symptoms include CPEO, lid lag, slow saccades, and cataracts. Distal muscle weakness is common, with patients reporting difficulties with activities requiring fine motor control of hands. Myotonia most consistently involves the hand muscles, which can be observed  as “percussion myotonia”, and myotonia of the facial muscles, tongue, and other bulbar muscles results in impairment of facial expressions, chewing, talking, and swallowing.