What are the genetic changes related to myasthenia gravis ?
Researchers believe that variations in particular genes may increase the risk of myasthenia gravis, but the identity of these genes is unknown. Many factors likely contribute to the risk of developing this complex disorder.  Myasthenia gravis is an autoimmune disorder, which occurs when the immune system malfunctions and attacks the body's own tissues and organs. In myasthenia gravis, the immune system disrupts the transmission of nerve impulses to muscles by producing a protein called an antibody that attaches (binds) to proteins important for nerve signal transmission. Antibodies normally bind to specific foreign particles and germs, marking them for destruction, but the antibody in myasthenia gravis attacks a normal human protein. In most affected individuals, the antibody targets a protein called acetylcholine receptor (AChR); in others, the antibodies attack a related protein called muscle-specific kinase (MuSK). In both cases, the abnormal antibodies lead to a reduction of available AChR.  The AChR protein is critical for signaling between nerve and muscle cells, which is necessary for movement. In myasthenia gravis, because of the abnormal immune response, less AChR is present, which reduces signaling between nerve and muscle cells. These signaling abnormalities lead to decreased muscle movement and the muscle weakness characteristic of this condition.  It is unclear why the immune system malfunctions in people with myasthenia gravis. About 75 percent of affected individuals have an abnormally large and overactive thymus, which is a gland located behind the breastbone that plays an important role in the immune system. The thymus sometimes develops tumors (thymomas) that are usually noncancerous (benign). However, the relationship between the thymus problems and the specific immune system malfunction that occurs in myasthenia gravis is not well understood.  People with myasthenia gravis are at increased risk of developing other autoimmune disorders, including autoimmune thyroid disease and systemic lupus erythematosus. Gene variations that affect immune system function likely affect the risk of developing myasthenia gravis and other autoimmune disorders.  Some families are affected by an inherited disorder with symptoms similar to those of myasthenia gravis, but in which antibodies to the AChR or MuSK proteins are not present. This condition, which is not an autoimmune disorder, is called congenital myasthenic syndrome.