Kearns–Sayre syndrome

Kearns–Sayre syndrome (KSS), oculocraniosomatic disorder or oculocranionsomatic neuromuscular disorder with ragged red fibers is a mitochondrial myopathy with a typical onset before 20 years of age. KSS is a more severe syndromic variant of chronic progressive external ophthalmoplegia (abbreviated CPEO), a syndrome that is characterized by isolated involvement of the muscles controlling movement of the eyelid (levator palpebrae, orbicularis oculi) and eye (extra-ocular muscles). This results in ptosis and ophthalmoplegia respectively. KSS involves a combination of the already described CPEO as well as pigmentary retinopathy in both eyes and cardiac conduction abnormalities. Other symptoms may include cerebellar ataxia, proximal muscle weakness, deafness, diabetes mellitus, growth hormone deficiency, hypoparathyroidism, and other endocrinopathies. In both of these diseases, muscle involvement may begin unilaterally but always develops into a bilateral deficit, and the course is progressive. This discussion is limited specifically to the more severe and systemically involved variant.

KSS is caused by mitochondrial DNA rearrangements, typically large deletions of 1.1–10 kb, that impair oxidative phosphorylation and ATP production, leading to dysfunction in several tissues, particularly energy-demanding ones such as the brain and muscles. In 2024, novel mechanisms were discussed for the first time at the cellular and molecular levels by Mazyar Yazdani (Oslo University Hospital), including ROS overproduction, inhibition of protein synthesis, myelin vacuolation, demyelination, autophagy, apoptosis, and involvement of lipid rafts and oligodendrocytes.