Differential diagnosis


CPEO must be differentiated from other disorders associated with ophthalmoplegia. These include isolated CPEO, oculopharyngeal muscular dystrophy, myotonic dystrophy, isolated oculopharyngeal myopathy, and mendelian CPEOs associated with multiple deletions of mtDNA such as POLG

It is Kearns-Sayre syndrome

Kearns-Sayre syndrome (KSS) is a clinical subtype of chronic progressive external ophthalmoplegia (CPEO).

KSS is defined by the following triad: onset before the age of 20, CPEO, and pigmentary retinopathy. Affected individuals have at least 1 of the following conditions: complete heart block, cerebrospinal fluid (CSF) protein of more than 100 mg/dL, cerebellar ataxia, short stature, deafness, dementia, and endocrine abnormalities.

Pathophysiology

In KSS muscle fibers stains demonstrate ragged red fibers like in other mitochondrial myopathies.

Postmortem ophthalmic pathology reveals atrophy of the retinal pigment epithelium and outer retina accompanied by the aberrant pigment in all layers of the sensory retina most marked posteriorly, in contrast to the preservation of peripheral retinal rods and cones. This pattern of photoreceptor degeneration led to the theory that the primary defect producing the retinopathy of KSS is in the retinal pigment epithelium.

Furthermore, postmortem neuropathology of patients with KSS can sometimes be associated with severe demyelination of the white matter tracts of the brain. It is not known why the loss of myelin occurs

Symptoms

Chronic Progressive External Ophthalmoplegia

Mitochondrial myopathy characterized by drooping of the eyelids (ptosis) and paralysis of the extraocular muscles (ophthalmoplegia).

Pigmentary Retinopathy

In patients with pigmentary retinopathy, there is a migration of retinal pigment epithelial (RPE) cells or macrophages containing melanin into the retina. Hence, pigmentary retinopathy is the final common outcome of many retinal and chorioretinal disorders and often a common manifestation of numerous metabolic and neurodegenerative diseases.

Retinitis pigmentosa is the name given to a large group of hereditary retinal degenerations that share the common feature of progressive damage to the photoreceptor–pigment epithelial complex. Pigmentary retinopathy can mimic retinitis pigmentosa phenotypically because of the presence of characteristic pigmentary changes in the retina. Moreover, visual symptoms in retinitis pigmentosa such as night blindness or diminished visual acuity can also be manifest in pigmentary retinopathy.

Electroretinography (ERG) is usually normal or mildly abnormal in pigmentary retinopathy, whereas the ERG analysis demonstrates severely depressed or extinguished scotopic responses and less severely reduced photonic cone responses compared to retinitis pigmentosa.

Non-muscular Neurologic Dysfunction

The following abnormalities could be observed: cerebellar ataxia, sensorineural hearing loss, neuropathy, and impaired intellectual function.

Endocrine Disorders

Endocrine dysfunction can be the initial presenting symptom preceding other neurological manifestations of KSS. The frequency of endocrine disturbances has been reported to range from 35% to 67%, including the following: diabetes mellitus, short stature and growth hormone insufficiency, hypogonadotropic hypogonadism, adrenal insufficiency, and primary hypoparathyroidism. Therefore, endocrinologists should be aware of possible multiple-endocrine complications and regularly screen for them, given that these are potentially treatable aspects of this disease.

Cardiac Conduction Disturbances

Patients with KSS may develop cardiac conduction disorders at any time. Abnormalities range from simple PR interval prolongation to infranodal high-degree atrioventricular (AV) block. This predisposes the patients to stroke or sudden death from the direct effects of an arrhythmia or a cardiac embolus.

Non-Ocular Muscle Weakness

In some patients with KSS, the facial muscles can become affected. Involvement of orbicularis oculi muscles affects the ability to close the eyelids tightly, whereas involvement of the frontalis muscle hinders opening of already ptotic eyelids.

Occasionally, patients experience dysphagia when the muscles of mastication get involved.

With the progression of the disease, weakness of the neck and shoulder muscles can develop as well as the mild weakness of the extremities muscles.

Diagnosis

Following triad: onset before the age of 20, CPEO, and pigmentary retinopathy. Affected individuals have at least 1 of the following conditions: complete heart block, cerebrospinal fluid (CSF) protein of more than 100 mg/dL, cerebellar ataxia, short stature, deafness, dementia, and endocrine abnormalities.