Kearns–Sayre syndrome (KSS) is a rare neuromuscular disease with onset usually before 20 years of age. 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. Kearns-Sayre syndrome is characterized by progressive limitation of eye movements until there is complete immobility, accompanied by eyelid droop. It is also associated with abnormal accumulation of pigmented material on the membrane lining the eyes (retina). Additional symptoms may include mild skeletal muscle weakness, heart block (a cardiac conduction defect), short stature, hearing loss, an inability to coordinate voluntary movements (ataxia), impaired cognitive function, and diabetes. Seizures are infrequent. Several endocrine disorders can be associated with KSS.
Kearns-Sayre is the result of deletions in mitochondrial DNA (mtDNA) that cause a particular phenotype. mtDNA is transmitted exclusively from the mother's ovum. Mitochondrial DNA is composed of 37 genes found in the single circular chromosome measuring 16,569 base pairs in length. Among these, 13 genes encode proteins of the electron transport chain (abbreviated "ETC"), 22 encode transfer RNA (tRNA), and two encode the large and small subunits that form ribosomal RNA (rRNA). 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.
Kearns-Sayre Syndrome is a more severe syndromic variant of chronic progressive external ophthalmoplegia (CPEO), a syndrome that is characterized by isolated involvement of the muscles controlling eyelid movement. This results in ptosis and ophthalmoplegia respectively. KSS involves a triad of the already described CPEO, as well as bilateral pigmentary retinopathy, and cardiac conduction abnormalities. Other areas of involvement can include cerebellar ataxia, proximal muscle weakness, deafness, diabetes mellitus, growth hormone deficiency, hypoparathyroidism, or other endocrinopathies. In both of these diseases, muscle involvement may begin unilateral but always develops into a bilateral deficit, and the course is progressive.