What is Myotonia Congenita?
Myotonia congenita (MC) is a genetic disorder affecting our skeletal muscles, which are the muscles we can consciously control. The hallmark of this condition is myotonia, which is when muscles have trouble relaxing after they contract, leading to stiffness, cramps, and unusually large muscles. MC is caused by changes in the CLCN1 gene, a gene responsible for creating chloride channels, which help regulate muscle contractions. If these channels don’t work right, our muscles can become overly excited, causing them to contract repetitively and lead to myotonia.
In the past, experts classified MC into two main types: Becker disease and Thomsen disease. Becker disease is a more severe form of MC that is inherited from both parents and can eventually lead to permanent muscle weakness. On the other hand, Thomsen disease typically appears earlier in childhood with milder symptoms and is inherited from just one parent. However, more recent research encountering over 200 different mutations in the CLCN1 gene has blurred this classification, reflecting a broader diversity in ways MC can present itself.
What Causes Myotonia Congenita?
Myotonia in a condition called Myotonia Congenita (MC) happens due to a faulty muscle protein brought about by genetic mutations in the CLCN1 gene. This protein, known as CIC-1, is a kind of “gate” that controls the flow of chloride ions (a type of charged particle) in and out of muscle cells, and plays a critical role in how those cells function and communicate with each other. When the CIC-1 protein isn’t working properly, the muscle cells can become too easily triggered, which leads to hyperactivity.
The main job of CIC-1 protein in muscle cells is to make it harder to generate muscle contractions. This happens because they block the flow of chloride ions, which help to control the electrical activity of our muscles, thus preventing the uncontrolled muscle contractions characteristic of this condition. Because these proteins represent the majority of the ones maintaining this control, losing their function significantly affects how the muscles respond to signals.
Furthermore, normally, the CIC-1 proteins help to balance the buildup of positively charged particles, specifically potassium ions, in the space around muscle cells. These ions build up when muscle cells fire many signals, which happens during repeated or continuous muscle activity. However, in MC, without the balance provided by CIC-1 proteins, even small changes in potassium concentration can trigger uncontrolled muscle activity leading to myotonia (muscle stiffness). This also explains why treatments for MC often target a different type of cellular gate for Sodium ions, with the aim of reducing the extra sensitivity and activity in the muscle cells.
Risk Factors and Frequency for Myotonia Congenita
Myotonia congenita (MC), a medical condition, was once reported to occur in 1 out of every 23,000 people for the inherited version called Thomsen disease, and 1 out of every 50,000 people for the non-inherited version known as Becker disease. However, it’s now understood that the inherited form – Thomsen disease, is actually less common than Becker disease. A study conducted in the United Kingdom, involving 300 MC patients, found that only 37% of them had the inherited type of the condition.
Interestingly, this condition is found more often in Northern Scandinavia, with 1 out of every 10,000 people having it. This rate is ten times more than the estimated prevalence of MC globally.
Signs and Symptoms of Myotonia Congenita
Myotonia congenita (MC) is a disorder that involves muscles taking too long to relax after they’ve been contracted. Even though it can be inherited in two different ways, it’s still quite hard to diagnose and manage, because the symptoms can vary a lot. Even family members with the same genetic changes can have different symptoms which adds to the complexity. But sometimes, specific genetic changes can lead to a very predictable set of symptoms. Thorough medical histories of family members are often helpful in figuring out how it’s been inherited, although sometimes the problem just happens out of the blue.
Young children might have trouble swallowing, spit up a lot, cough when eating or drinking, and choke. They might be clumsy and fall a lot, even if they already know how to walk. They might also have trouble opening their eyes after they’ve been crying for a while. These signs can be easy to miss, so it’s really important for healthcare providers to pay careful attention to what the patient and their caregivers report, as well as what they observe in their examination. Symptoms usually get worse at first but then level off.
Interestingly, exercise or repetitive movements can often help ease the muscle stiffness seen in this condition, an effect nicknamed the “warm-up” phenomenon. This benefit unfortunately disappears quickly once the activity stops. Additionally, men tend to be more impacted than women, and women can see their symptoms get worse during pregnancy and menstruation. These patterns suggest that sex hormones might influence how the body’s chloride channels work.
There are two types of MC, which are defined based on how they’re inherited, and they have slightly different features.
- Becker disease (BD): BD is a form of MC that is inherited in an autosomal recessive manner. It often leads to moderate to severe muscle stiffness and temporary weakness, which can become long-term in some cases. BD generally appears later in childhood than Thomsen disease (TD), and it often leads to bigger muscles, especially in the lower body.
- Thomsen disease (TD): TD is a form of MC that is inherited in a dominant manner and generally leads to milder symptoms but these start sooner than in BD. Unlike BD, TD does not involve progressivel permanent weakness. The extent of symptoms in TD can vary quite a bit, even among family members with the same genetic mutation.
Testing for Myotonia Congenita
Doctors can check for signs of Myotonia, a condition causing muscle stiffness, by asking patients to repeatedly perform simple actions like opening and closing their eyes or fist. People with Myotonia might find it difficult to immediately open their hand after shaking hands – this is known as the “warm-up effect”.
Additional tests like checking blood for creatinine kinase, a substance that increases when muscle damage occurs, can also be conducted. Although it’s not always the case, levels can sometimes be up to three to four times higher than normal when Myotonia is present.
Doctors may also use a test called electromyography, which measures the electrical activity in muscles. But this test can be time-consuming, uncomfortable, and its results might overlap with other similar muscle conditions, making it harder to distinguish between them. Through this test, doctors can identify a pattern of electric activity that’s common in Myotonia patients. But electromyography doesn’t help differentiate between the two types of Myotonia.
There’s another test known as a muscle biopsy which involves taking a small sample of muscle tissue for examination. However, due to advancements in genetic testing, muscle biopsies are now done rarely. Even if done, it may show an increased number of muscle fibers with more nuclei and fewer of a type called 2B fibers.
Genetic testing is often considered the most reliable method and is used for diagnosing Myotonia. This is performed by analyzing specific genes such as CLCN1 and SCN4A, which are associated with muscle function. Sometimes, even if the patient has symptoms of Myotonia, the CLCN1 gene mutation may not be identified, indicating that the condition might be caused by unknown genetic factors. Therefore, selecting the appropriate genetic testing techniques should be done at specialized centres to help interpret the results more accurately and to lower the costs. If the standard panel of multiple gene testing doesn’t reveal the cause, more comprehensive genomic techniques involving examination of all the genes in the genome (exome sequencing) or in the mitochondria (mitochondrial sequencing) might be considered.
Treatment Options for Myotonia Congenita
Not every patient with Myotonia Congenita (MC), a condition that impacts muscle stiffness, needs to take medication. It’s a good idea to have a check-up with a neurologist who can help decide if medication is necessary. Some people might also find it helpful to adjust their lifestyle, like steering clear of stress and cold temperatures, both of which can trigger symptoms.
Exercise, specifically gymnastics, could potentially offer some benefits, but more research is needed to confirm its effect. If medication is prescribed, it’s usually designed to reduce the muscle’s oversensitivity by controlling the flow of sodium ions, which are particles that carry electric charges and influence muscle functioning.
A commonly prescribed drug is Mexiletine, which is similar to a local anesthetic called lidocaine. This medicine is often used to manage irregular heart rhythms by controlling the sodium influx during the heart’s electrical activity. However, it’s important to monitor heart activity before and during its use to ensure safety. This drug may cause side effects like trembling, feeling dizzy, unsteady movements, and stomach issues, although these typically go away either by reducing the dose or stopping the medication.
Other drugs, such as anticonvulsants like phenytoin, are also sometimes used. Another potential treatment targets potassium channels, which are another part of cell communication. Retigabine, a drug that stimulates these channels, has shown promise in easing myotonia severity in mouse studies.
While these options offer some hope, there’s still a lot we don’t know about the best way to manage MC with medication. More research is needed to uncover the most effective treatments.
What else can Myotonia Congenita be?
MC, or Myotonia Congenita, is the most common type of non-dystrophic myotonia, meaning that the disease doesn’t cause the structure of the muscle tissue to deteriorate. Instead, in MC, you’ll find that muscle stiffness occurs due to defects in the ion channels in our muscles, which lead to problems with the flow of ions. Other conditions that also result from issues with ion channels – specifically sodium ion channels – include paramyotonia congenita (PMC), potassium-aggravated myotonia (PAM), and potassium-sensitive (hyperkalemic) periodic paralysis (HyperPP).
These latter disorders are caused by mutations in the SCN4A gene, which negatively impacts the function of certain sodium channels. The symptoms can vary depending on the specific disorder; for example, people with MC typically have more issues with their lower limbs – they might find it challenging to stand up quickly – whereas those with PAM often experience more severe symptoms in their eyes and face. Meanwhile, the myotonia or muscle stiffness associated with HyperPP is minor and usually affects areas like the eyelids and the tongue.
To tell MC apart from these other disorders, medical professionals take into account the factors that may make the symptoms worse or lessen them, whether there’s any disease outside the muscle, and the results of an electromyography test, which can measure the electrical activity of muscles. The conditions caused by problems with potassium channels can be recognized by the fact that the symptoms often get worse after eating foods high in potassium. Patients might describe their muscle stiffness as being painful, which isn’t a common characteristic of MC.
Besides these potassium channel disorders, doctors also need to think about the possibility of myotonic dystropheis when they see muscle weakness and stiffness, especially in young children and babies. Myotonic dystrophy type I and II are accompanied by systemic features including hormonal imbalances, heart rhythm problems, and the formation of cataracts. Moreover, the pattern of muscle weakness seen in myotonic dystrophy is very different from the one seen in MC.
What to expect with Myotonia Congenita
Neither type of Myotonia Congenita (MC), whether it’s inherited from one or both parents, leads to broader health issues or limits lifespan. This makes it crucially different from Myotonic Dystrophy, a more severe muscle disorder. After the first signs of MC appear, these conditions usually don’t get worse over time.
Becker disease, one form of MC, is generally considered to have more serious symptoms than Thomsen disease, another form of MC, and patients may continue to experience muscle weakness for a long time. To make sure patients can make no-regrets decisions about starting a family, they should have access to genetic counseling services to understand the risks of passing MC onto their children.
Possible Complications When Diagnosed with Myotonia Congenita
During anesthesia, special care needs to be taken in patients with muscle condition (MC), as certain muscle relaxants like depolarizing ones can lead to serious muscle spasms and problems with second round breathing efforts. Some drugs may cause more harm to MC patients, so they should be used very carefully if required, these include:
- Suxamethonium – This can cause intense muscle spasms and problems with breathing.
- Adrenaline and beta-agonists – These can increase the intensity of symptoms.
- Beta antagonists – These can potentially worsen the severe symptoms.
- Colchicine – This can activate muscle disease, especially in individuals with kidney problems.
Moreover, pregnancy can worsen the muscle condition, so it’s important to have a team of healthcare professionals during the whole pregnancy, birth and post-birth period.
Preventing Myotonia Congenita
Education and support are crucial for patients dealing with Myotonia Congenita (MC), a genetic disorder involving prolonged muscle stiffness, and their families. MC can greatly impact a person’s physical appearance, which can in turn deeply affect their mental health. Additionally, because MC often leads to muscle enlargement, patients may look healthy and strong, leading to unfair mistreatment or discrimination.
Patients may attempt to resist the muscle stiffness, which can actually make it worse. Stress has also been known to make symptoms worse. Thus, it’s important that patients develop effective ways to manage stress and prioritize their mental health to improve their overall functioning.
Another vital step is adjusting the patients’ surroundings, like their home, school, or workplace, in order to reduce the risk of falls. These changes should also aim to minimize any harm that might happen if a patient does fall. Changes to their diet might also be necessary to make swallowing easier and safer, reducing the chances of accidentally inhaling food or drink.
