Congenital myasthenia gravis differs from other forms of myasthenia gravis (MG) because it is caused by a genetic defect rather than an abnormal immune system response.
While the symptoms are very similar to immune-related myasthenia gravis, congenital myasthenia gravis, also called congenital myasthenic syndrome, results from changes in genes involved in neuro-muscular communication. Congenital MG symptoms may arise anytime from birth into adulthood.
Congenital myasthenia gravis is usually inherited in an autosomal recessive pattern, meaning that a person must receive a copy of the defective gene from both parents to develop the disease. If a person has only one copy of the defective gene, they will be a carrier but not show any symptoms.
One form of congenital MG, called slow-channel congenital myasthenia gravis, is inherited in an autosomal dominant pattern. In this case, just one copy of the defective gene can cause a person to develop the disease.
Types of congenital myasthenia gravis
There are various types of congenital myasthenia gravis that are defined by the location and type of genetic defect that causes poor neuromuscular signaling.
The points where nerves communicate with muscles are called neuromuscular junctions. When a nerve impulse is sent to direct a muscle to contract, the nerve cell releases a chemical signaling molecule called a neurotransmitter — such as acetylcholine — into the neuromuscular junction.
Acetylcholine then binds to the acetylcholine receptors on the muscle cells, causing the receptors to open and allow a change in electrical current across the cell membrane. This electrical change triggers the muscles to contract.
Presynaptic congenital myasthenia gravis is caused by a mutation that results in the nerve cells not releasing sufficient acetylcholine into the neuromuscular junction. This results in poor signal strength. There are multiple genetic mutations that can affect acetylcholine release.
Postsynaptic congenital myasthenia gravis can be caused by various genetic mutations which result in the muscle cells having too few acetylcholine receptors or having defective receptors, on the other side of the neuromuscular junction. Sometimes, mutations result in defective acetylcholine receptors that do not stay open long enough. These are called fast-channel receptors and they disrupt the electrical current needed to trigger muscle contraction.
In another form of postsynaptic congenital myasthenia gravis, receptors stay open too long. This is called slow-channel congenital myasthenia gravis. Again, this disrupts the electrical current needed to trigger muscle contractions.
Synaptic congenital myasthenia gravis is caused by a lack of acetylcholinesterase, the enzyme that breaks down acetylcholine. This results in too much acetylcholine lingering in the neuromuscular junction and disrupted signaling.
Because congenital MG is a genetic disorder rather than an immune disorder, it does not respond to immunosuppressive drugs. Scientists are researching ways to address the underlying genetic causes of the disease. Different medications are available that may help treat some forms of congenital myasthenia gravis.
Presynaptic congenital myasthenia gravis and fast channel congenital myasthenia gravis may be treated with 3,4-diaminopyridine or cholinesterase inhibiting medications, which increase the amount of acetylcholine in the neuromuscular junction. But these medications may worsen other forms of congenital myasthenia gravis, such as slow-channel congenital myasthenia gravis.
Slow-channel congenital myasthenia gravis may be treated with fluoxetine, which blocks the acetylcholine receptor and reduces the length of time the receptors stay open. Treatment options for synaptic congenital myasthenia gravis are limited, but ephedrine and albuterol may have beneficial effects.
Genetic tests to identify the form of congenital myasthenia gravis affecting the patient is critical because treatments that are beneficial to some forms may be detrimental to others.
Congenital myasthenia gravis is a challenging disease. There are a number of organizations that offer support for patients and their families and caregivers.
These include the Myasthenia Gravis Foundation of America, the American Autoimmune & Related Diseases Association, and the Muscular Dystrophy Association.
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