Inherited myopathies are caused by mutations, or changes, in genes — the blueprints for making proteins that are necessary for our bodies to function correctly. Genes are responsible for building our bodies; we inherit them from our parents — along with any mutations or defects they have — and pass them on to our children.
Causes of inherited myopathies
Many of the inherited myopathies are caused by mutations that interfere with ion channels, causing either too much or too little current from flowing through the muscle cells. These disorders (myotonia congenita, paramyotonia congenita, periodic paralysis and central core disease) are sometimes called channelopathies.
Central core disease seems to damage, and thus weaken, muscles by causing an excess release of calcium from internal storage compartments.
A fifth myopathy, nemaline myopathy, is caused by mutations that affect filament proteins. When the filament proteins fail to do their jobs, muscles can’t contract properly, causing a loss of tone and strength.
At least one myopathy (a type of myotubular myopathy) is caused by mutations in a muscle protein required for normal muscle development. When this protein is absent or inactive, the muscles don’t form properly.
In the inherited myopathies, genetic mutations cause defects in various proteins necessary for muscle tone and contraction.
Muscle tone and contraction
Contraction is the forceful shortening or tightening of muscle, which pulls on the joints to cause movement. In other words, when your brain “tells” a muscle to move, you cause it to contract, and it’s then able to do what you’re asking.
Muscle tone refers to a readiness for contraction that makes resting muscle resistant to stretching. A toned muscle holds its shape and elasticity and is able to respond by contracting when you want it to move. Bodies with poor muscle tone appear “floppy.” Good muscle tone is important for posture and coordination.
A skeletal muscle’s tone and contraction depend on its ability to respond to stimulation from nerve cells, which relay signals from the brain, such as the decision to move your hand or leg. A muscle is actually a bundle of individual muscle cells, and a cluster of muscle cells stimulated by a single nerve cell is called a motor unit.
The process of muscle contraction begins when the nerve cells release chemical signals onto the muscle cells. These signals cause the opening of ion channels, pores in each muscle cell’s outer surface that open and close to regulate the movements of charged atoms called ions.
Different types of ion channels allow specific ions — sodium, calcium, potassium or chloride — to pass into and out of the muscle cell, creating electrical currents. Opening of sodium and calcium channels causes an electrical excitation that leads to contraction, while opening of potassium and chloride channels keeps the excitation from occurring. (See How Ion Channels Regulate Muscle Contraction.)
The purpose of the electrical excitation is to rapidly spread the signal to contract throughout the entire muscle cell, and to stimulate the opening of still more channels that release calcium from internal compartments in the muscle cell.
Finally, the freed calcium ions trigger muscle contraction by stimulating the sliding action of filament proteins. These rodlike proteins run lengthwise within the muscle cell and are anchored at opposite ends by scaffolds called Z-discs. When the filament proteins slide past each other — in a ratchet-like mechanism that is fueled by cellular energy sources — they cause shortening of the muscle cell and shortening (contraction) of the whole muscle.
If this process is disrupted at any stage between the nerve’s signaling the muscle and the filament proteins’ action, the muscle loses its normal capacity for tone and contraction. At one extreme, the muscle might be limp and weak, and at the other extreme, the muscle may be involuntarily active and unable to relax.
Causes of noninherited myopathies
Noninherited myopathies are caused by an excess or a deficiency of hormones made by the thyroid gland, which is part of the endocrine system. These myopathies are known as endocrine myopathies.
Inheritance patterns in myopathies
On being told they have a genetic disorder such as an inheritable myopathy, patients often ask, “But it doesn’t run in the family, so how could it be genetic?” Inheritable myopathies can run in a family, even if only one “blood relative” in the family has it.
This is because genetic diseases like inheritable myopathies can be inherited in a variety of ways: X-linked,autosomal dominant and autosomal recessive. Or, a new, spontaneous mutation may occur for the first time in a child.
X-linked means that the genetic mutation (or defect) is located on the X chromosome. For many X-linked diseases, a normal copy of the gene can compensate for the defective copy. Because males have only one X chromosome while females have two, X-linked diseases almost always affect males.
Autosomal means the mutation occurs on a chromosome other than the X or Y. Therefore, autosomal diseases affect males and females equally.
Autosomal recessive means that two copies of a defective gene are required for the full-blown disease. One copy is inherited from each parent, neither of whom would normally have the disease but would be a “carrier.”
Autosomal dominant means that one copy of a defective gene is enough to cause disease. So, a person who inherits the defective gene from a parent will have the disease, as will the parent.
Inheritable myopathies passed on in an autosomal dominant pattern can be easy to trace through the family tree. By contrast, X-linked or autosomal recessive disorders might seem to occur “out of the blue.” But in reality, one or both parents might be carriers who silently harbor a genetic mutation. Many parents have no idea they’re carriers of a disease until they have a child with the disease.
Spontaneous mutations do come “out of the blue,” when a new mutation occurs during the child’s conception. After they occur, these mutations can be passed on to the next generation.
A good way to find out more about your risk of inheriting or passing on an inheritable myopathy is to talk to your MDA clinic physician or a genetic counselor. Also, see Facts About Genetics and Neuromuscular Diseases.