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