Kearns-Sayre syndrome ..., (Kearns-Sayre syndrome) - mitochondrial DNA.

The Kearns-Sayre syndrome is a disorder that affects many parts of the body, especially the eyes. The features of Kearns-Sayre syndrome usually appear before 20 years of age. Signs and symptoms include progressive external ophthalmoplegia and pigmentary retinopathy causing degeneration of the retina and can lead to vision loss. In addition, affected individuals have at least one of the following signs or symptoms: cardiac conduction defects, ataxia or abnormally high concentrations of protein in the cerebrospinal fluid.

In addition, individuals with Kearns-Sayre syndrome may also have muscle weakness in the limbs, deafness, kidney problems and dementia. People usually have short stature. Occasionally, diabetes mellitus.

The Kearns-Sayre syndrome is of a disturbance due to defects in mitochondria, where oxidative phosphorylation is performed. Although most of the DNA is on chromosomes within the nucleus (nuclear DNA), mitochondria also have a small amount DNA, called mitochondrial DNA (mtDNA). In humans, the mitochondrial DNA comprises some 16,500 base pairs, which represent a small fraction of the total DNA in the cells. Mitochondrial DNA contains 37 genes, all essential for normal mitochondrial function. Thirteen of these genes encode enzymes involved in oxidative phosphorylation. Oxidative phosphorylation is a process that uses oxygen and simple carbohydrates to produce adenosine triphosphate (ATP), the main energy source of the cell. The remaining genes encode molecules called transfer RNA (tRNA) and ribosomal RNA (rRNA). These types of RNA help assemble amino acids in functional proteins.

People with Kearns-Sayre syndrome have a large deletion of mtDNA, ranging from 1,000 to 10,000 nucleotides. The reason for this deletion in affected individuals is unknown. MtDNA deletions that give rise to Kearns-Sayre syndrome cause loss of genes important for mitochondrial protein formation and oxidative phosphorylation. The most common deletion removes 4997 nucleotides, which includes twelve mitochondrial genes. MtDNA deletions affect oxidative phosphorylation lead to a decrease in cellular energy production. Whether genes are deleted, all the steps of oxidative phosphorylation are affected. It is unclear how these deletions lead to specific signs and symptoms of Kearns-Sayre syndrome, although the characteristics of the disease are probably related to the lack of cellular energy. It is believed that the eyes are frequently affected by mitochondrial defects because they are especially dependent on mitochondria for energy.

This disease usually not inherited, but arises from mutations that occur in the body cells after conception. This alteration is called somatic mutation and is present only in certain cells. Rarely, the Kearns-Sayre syndrome is inherited mitochondrial pattern, also known as maternal inheritance. This pattern of inheritance is applied to genetic alterations involving mitochondrial DNA. Mitochondrial disorders can appear in each generation of a family and can affect both men and women, but parents do not pass mitochondrial traits to their children.

Tests in IVAMI: in IVAMI perform detection of mutations associated with Kearns-Sayre syndrome, by PCR amplification of complete deletions in mitochondrial DNA.

Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).