Description Kearns-Sayre syndrome is a condition that affects many parts of the body, especially the eyes. The features of Kearns-Sayre syndrome usually appear before age 20, and the condition is diagnosed by a few characteristic signs and symptoms. People with Kearns-Sayre syndrome have progressive external ophthalmoplegia , which is weakness or paralysis of the eye muscles that impairs eye movement and causes drooping eyelids ptosis. Affected individuals also have an eye condition called pigmentary retinopathy, which results from breakdown degeneration of the light-sensing tissue at the back of the eye the retina that gives it a speckled and streaked appearance. The retinopathy may cause loss of vision.
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Onset is in the first and second decades of life. The first symptom of this disease is a unilateral ptosis , or difficulty opening the eyelids, that gradually progresses to a bilateral ptosis. As the ptosis worsens, the individual commonly extends their neck, elevating their chin in an attempt to prevent the eyelids from occluding the visual axis. Along with the insidious development of ptosis, eye movements eventually become limited causing a person to rely more on turning the head side to side or up and down to view objects in the peripheral visual field.
Pigmentary retinopathy[ edit ] Retinitis pigmentosa, mid stage KSS results in a pigmentation of the retina , primarily in the posterior fundus.
The appearance is described as a "salt-and-pepper" appearance. There is diffuse depigmentation of the retinal pigment epithelium with the greatest effect occurring at the macula. This is in contrast to retinitis pigmentosa where the pigmentation is peripheral. The appearance of the retina in KSS is similar to that seen in myotonic dystrophy type 1 abbreviated DM1.
Modest night-blindness can be seen in patients with KSS. This often progresses to a Third-degree atrioventricular block , which is a complete blockage of the electrical conduction from the atrium to the ventricle. Symptoms of heart block include syncope , exercise intolerance , and bradycardia. Cerebral folate deficiency[ edit ] Kearns-Sayre patients are consistently found to have cerebral folate deficiency , a syndrome in which 5-MTHF levels are decreased in the cerebrospinal fluid despite being normal in serum.
Kearns—Sayre syndrome occurs spontaneously in the majority of cases. In some cases it has been shown to be inherited through mitochondrial, autosomal dominant, or autosomal recessive inheritance. There is no predilection for race or sex, and there are no known risk factors. As of there were only cases reported in published literature. The 13 proteins involved in the ETC of the mitochondrion are necessary for oxidative phosphorylation. Mutations in these proteins results in impaired energy production by mitochondria.
This cellular energy deficit manifests most readily in tissues that rely heavily upon aerobic metabolism such as the brain, skeletal and cardiac muscles, sensory organs, and kidneys. This is one factor involved in the presentation of mitochondrial diseases. There are other factors involved in the manifestation of a mitochondrial disease besides the size and location of a mutation.
Mitochondria replicate during each cell division during gestation and throughout life. Because the mutation in mitochondrial disease most often occurs early in gestation in these diseases, only those mitochondria in the mutated lineage are defective. This results in an uneven distribution of dysfunctional mitochondria within each cell, and among different tissues of the body.
This describes the term heteroplasmic which is characteristic of mitochondrial diseases including KSS. The distribution of mutated mtDNA in each cell, tissue, and organ, is dependent on when and where the mutation occurs. A publication in by Fischel-Ghodsian et al. One of the patients had characteristic KSS, while the other patient had a very different disease known as Pearson marrow pancreas syndrome.
The most common deletion is 4. An individual should be suspected of having KSS based upon clinical exam findings. Suspicion for myopathies should be increased in patients whose ophthalmoplegia does not match a particular set of cranial nerve palsies oculomotor nerve palsy , fourth nerve palsy , sixth nerve palsy. Initially, imaging studies are often performed to rule out more common pathologies. Biopsy findings[ edit ] It is not necessary to biopsy an ocular muscle to demonstrate histopathologic abnormalities.
In muscle fibers containing high ratios of the mutated mitochondria, there is a higher concentration of mitochondria. This gives these fibers a darker red color, causing the overall appearance of the biopsy to be described as " ragged red fibers. Abnormalities may also be demonstrated in muscle biopsy samples using other histochemical studies such as mitochondrial enzyme stains, by electron microscopy, biochemical analyses of the muscle tissue ie electron transport chain enzyme activities , and by analysis of muscle mitochondrial DNA.
Because it is a rare condition, there are only case reports of treatments with very little data to support their effectiveness. Several promising discoveries have been reported which may support the discovery of new treatments with further research. Satellite cells are responsible for muscle fiber regeneration. Shoubridge et al. In the forementioned study, regenerating muscle fibers were sampled at the original biopsy site, and it was found that they were essentially homoplasmic for wildtype mtDNA.
One study described a patient with KSS who had reduced serum levels of coenzyme Q In KSS, implantation of pacemaker is advised following the development of significant conduction disease, even in asymptomatic patients. Kearns , MD. Other cases had noted a peculiar pigmentation of the retina, but none of these publications had documented these three pathologies occurring together as a genetic syndrome.
Miller, Neil R. Orphanet J Rare Dis.
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