Congenital myasthenia gravis differs from other forms of myasthenia gravis (MG) because it is caused by a genetic defect rather than an abnormal immune response.
While symptoms are very similar to immune-related MG, congenital MG, also known as congenital myasthenic syndrome, results from changes in genes involved in nerve-muscle communication. Symptoms of congenital MG may arise anytime, from birth to adulthood. However, people who develop the condition later in life tend to have less-severe symptoms.
Inheritance
Congenital MG usually is inherited in an autosomal recessive manner, meaning that a person must receive a copy of the defective gene from both parents to develop the disease.
One form of congenital MG, called slow-channel congenital MG, is inherited in an autosomal dominant pattern, meaning that just one copy of the defective gene is sufficient to cause a person to develop the disease.
Types of congenital MG
There are various types of congenital MG, depending on the location and type of genetic defect that causes poor neuromuscular signaling.
The points where nerves come into contact and communicate with muscles are called neuromuscular junctions. When a nerve impulse is sent to direct a muscle to contract, a nerve cell releases a chemical signaling molecule called acetylcholine into the neuromuscular junction.
Acetylcholine then binds to acetylcholine receptors on muscle cells, causing them to open and allow for an influx of electrical current, which then triggers muscles to contract.
Presynaptic congenital MG
Presynaptic congenital MG is caused by a mutation that causes nerve cells to be unable to release sufficient amounts of acetylcholine into the neuromuscular junction. This effectively reduces the strength of the signal reaching muscles, which leads to muscle weakness. There are multiple genetic mutations that can affect acetylcholine release.
Postsynaptic congenital MG
Postsynaptic congenital MG can be caused by various genetic mutations that cause muscle cells to have either too few acetylcholine receptors, or defective receptors.
Sometimes, mutations cause acetylcholine receptors not to stay open long enough. In this form of the disease, known as fast-channel congenital MG, the malfunction disrupts the electrical current needed to trigger muscle contraction.
In another form of postsynaptic congenital MG, called slow-channel congenital MG, receptors stay open too long. Again, this disrupts the electrical current needed to provoke muscle contractions.
Synaptic congenital MG
This type of congenital MG 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 disrupting neuromuscular signaling.
Treatment and prognosis
There are no treatments to cure congenital MG. Treatments are designed to alleviate symptoms and target specific subtype of the disease.
Because congenital MG is a genetic disorder rather than an immune disorder, it does not respond to immunosuppressive agents. Scientists are looking for ways to address the underlying genetic causes of the disease. Different medications are available to help treat some forms of congenital MG.
Presynaptic congenital MG and fast-channel congenital MG may be treated with amifampridine (3,4-diaminopyridine) or cholinesterase inhibitors like Mestinon (pyridostigmine), which increase the amount of acetylcholine available in the neuromuscular junction. But these medications may worsen other forms of congenital MG, such as slow-channel congenital MG.
Slow-channel congenital MG may be treated with the antidepressant fluoxetine (sold as Prozac, among other brand names), which blocks acetylcholine receptors and reduces the time they remain open. Treatment options for synaptic congenital MG are limited, but ephedrine and albuterol may have beneficial effects.
Genetic tests to identify the specific form of congenital MG affecting a patient is critical, because treatments that are beneficial to some forms may be detrimental to others.
The prognosis depends on the subtype of the disease, the muscles affected, and the age at symptom onset. Children with difficulty breathing, feeding, or swallowing are likely to have pneumonia or respiratory failure. In some cases, muscle weakness is stable, does not worsen, or may even ease with time. Most patients without respiratory problems have a normal life expectancy.
Last updated: Nov. 16, 2021
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