A group of multiple hereditary diseases caused by an abnormal gene that cause muscle weakness, which worsens with physical activity, is called congenital myasthenic syndromes (CMSs). These syndromes happen quite rarely and they can affect any muscles involved in movement. These include muscles that control chewing, swallowing, speaking, blinking, breathing, and walking.
There are multiple congenital myasthenic syndrome types depending on the affected gene. The abnormal gene also determines many symptoms and severity of the condition. In most cases, CMSs are diagnosed at birth or early childhood. These syndromes often are lifelong.
CMSs are not curable but there are treatments that can lessen the symptoms and improve muscle weakness. In some cases, people develop a mild form of the disease and do not require treatment.
Symptoms
While these syndromes are diagnosed at birth, sometimes, they may not be diagnosed until childhood or early adulthood (rarely) if the symptoms are mild.
The symptoms may vary greatly among people with CMSs because they depend on the affected gene, muscles, and other factors. In any case, the most common symptom is muscle weakness that worsens with activity. Check below some symptoms according to the affected muscle:
- Facial muscle weakness
- Weak cry
- Difficulty swallowing and chewing
- Slurred or nasal speech
- Delayed crawling, walking, wrist development, and hand and finger skills (including combing hair or brushing teeth)
- Poor eye control (often happens with double vision) and drooping eyelids
- Breathing problems that may worsen with fever, stress, or infections
- Difficulty keeping the head in the upright position
Moreover, check some symptoms that may occur due to other congenital myasthenic syndrome types:
- Skeletal deformities (these include foot, spine, or joint deformities)
- Hearing loss (also known as deafness)
- Seizures
- Kidney problems
- Cognitive impairment (in rare cases)
- Weakness, pain, and numbness that happen in the hands and feet
- Abnormal facial features (including narrow jaw, wide-set eyes, and others)
If you notice that your child experiences any of the previous symptoms, immediately contact your healthcare provider.
Causes
There are more than 30 genes that cause CMSs, and the type of the disease depends on the gene. Healthcare providers divide CMSs according to the affected location, such as the neuromuscular junction (impulses) that provide signals between muscle and nerve cells to trigger movement (synapses). Loss of muscle function happens in different body parts, depending on where the signals are disrupted. For example:
- Presynaptic (where the impulse starts)
- Synaptic (the space between the muscle and nerve cells)
- The most common location is where the impulse is received (postsynaptic)
There are some CMS types that appear due to congenital disorders of glycosylation. A complex chemical process that plays an important role in communication between cells is called glycosylation. Problems with this chemical process may negatively affect the signals that come from nerves to the muscles.
However, in most cases, congenital myasthenic syndromes are inherited in an autosomal recessive pattern. It means both biological parents have the disease, but without any signs or symptoms. When biological children receive only one abnormal gene, these syndromes do not occur. Such children are carriers, meaning the abnormal gene may be passed to their children in the future.
In very rare cases, people may develop congenital myasthenic syndromes in an autosomal dominant pattern. It means you get only one abnormal gene.
Risk Factors
The risk of developing CMSs is high if both parents carry the abnormal gene that causes it. When the biological children inherit only one gene, these syndromes do not occur. However, the child carries the abnormal gene that may be passed to his/her children in the future.
Diagnosis
First, doctors will perform a physical examination (including a neurological examination) and ask some questions about your family history and symptoms. Thereafter, they will perform some tests to confirm the disease and exclude other conditions that cause similar symptoms. Check below some examples:
- Blood tests – These tests are done to check for the gene that causes CMSs and antibodies that disrupt signals between the muscles and nerve cells. Additional blood tests may be done to exclude other conditions.
- Electromyography (EMG) – This test is used to check the health of the muscles and nerves that control them. It may identify nerve and muscle dysfunction or problems with signals that travel between them.
- Repetitive nerve stimulation – This is a nerve conduction study used to measure the nerves’ ability to send signals. Usually, this test is performed multiple times to see if the ability of the nerves worsens with fatigue.
- Genetic testing – This test involves a blood sample tested in the laboratory to check for the abnormal gene that causes these syndromes.
- Cholinesterase challenge test – During this test, doctors will give you a medicine called Pyridostigmine to check if improvement in muscle fatigue happens.
- Other tests – These include lung function tests, a sleep study, muscle biopsy, and others.
Genetic Testing
This test can reveal the abnormal gene linked with congenital myasthenic syndromes. It may be helpful if you are planning to become pregnant. However, both biological parents should perform this test.
Treatment
In rare cases, people with mild symptoms do not need treatment. Check below some treatments often recommended by doctors for people with CMSs:
Medicines
The following medications cannot cure these syndromes, but may improve muscle strength and contraction. Physicians often prescribe different medications because it depends on the severity of the condition, the affected gene type, and other factors. Check below some examples:
- Acetazolamide
- 3, 4-diaminopyridine (3, 4-DAP), marketed as Amifampridine
- Albuterol
- Ephedrine
- Fluoxetine
- Neostigmine
- Pyridostigmine
Other Treatments
- Therapies – Some people need physical, speech, and occupational therapies to maintain muscle function.
- Breathing support – In some cases, people with CMSs may experience apnea (temporary pauses in breathing). Therefore, doctors often recommend noninvasive positive-pressure ventilation.
- Feeding support – In people with chewing problems, additional nutrition is required. Physicians usually recommend enteral nutrition (also called a feeding tube).
- Surgery – In severe cases, those who suffer from CMSs may need surgery for orthopedic deformities. These include surgery in the spine, feet, or surgical correction.
Frequently Asked Questions
What is congenital myasthenia syndrome?
This is a genetic disorder present at birth that causes problems with signals that travel between the muscle and nerve cells.
What is the life expectancy of someone with congenital myasthenia syndrome?
With treatment, these syndromes do not affect life expectancy.
What is the difference between myasthenia gravis and CMS?
Myasthenia gravis is an autoimmune disorder that is often treated with steroids, immunosuppressive medicines, and a thymectomy (in rare cases used). Congenital myasthenic syndromes are conditions that negatively affect the signals between nerves and muscle cells. If you have additional questions, ask your healthcare provider.
