Simply Stated: Understanding Myotonia Congenita

Myotonia congenita (MC) is a rare, inherited neuromuscular condition characterized by muscle stiffness (myotonia) present during infancy or childhood. Unlike some other neuromuscular disorders, MC does not cause progressive muscle loss (atrophy). So, while people with MC often appear muscular, they may struggle with everyday movements. It has been estimated that MC affects approximately 1 in 100,000 people worldwide, though the prevalence may be higher in some populations.

Symptoms and subtypes of myotonia congenita

Most people with MC begin experiencing muscle stiffness in early childhood, although onset may occur later in some cases. This stiffness can affect many parts of the body, including the face, tongue, and eyelids, hands and feet, and the arms and legs. People with MC often have enlarged (hypertrophic) muscles, but stiffness in these muscles leads to problems with coordination, quick movements, and the ability to relax muscles after use. Affected people may have trouble releasing their grip after a handshake, closing or opening their eyes, or walking smoothly. Many experience weakness specifically when starting a movement.

The symptoms of MC often worsen in cold temperatures. Repeated movements, however, typically improve muscle stiffness caused by MC; this is known as the warm-up phenomenon. While MC is a lifelong condition, it is usually non-progressive, which means that it does not worsen over time. As a result, many people with MC can adjust to living with this condition and maintain their daily functions long-term.

There are two main forms of MC, Thomsen disease and Becker disease, which differ in inheritance pattern and disease severity. Common features of these forms include the following:

Thomsen disease

• Autosomal dominant inheritance (one mutated gene copy causes the disease)
• Often less severe
• Begins earlier in life
• Does not involve muscle weakness

Becker disease

• Autosomal recessive inheritance (two mutated gene copies cause the disease)
• Often more severe
• Associated with pain, transient weakness, and occasionally, progressive weakness of distal muscles (hands, feet, lower arms/legs)

For more information about myotonia congenita symptoms, as well as diagnostic and management concerns, an overview can be found here.

Cause of MC

MC is caused by mutations in the CLCN1 gene, which encodes the ClC-1 chloride channel in muscle tissues. The condition primarily affects striated muscles, which include the skeletal muscles required for voluntary movements and the cardiac muscles required for pumping blood throughout the body. The ClC-1 chloride channel plays an important role in the ability of muscles to relax after contraction. When the channel does not function properly, muscles have difficulty relaxing, leading to stiffness.

Diagnosis of MC

MC is typically diagnosed using a variety of assessments including a thorough medical and family history, complete clinical examination, electrophysiological testing, and confirmatory genetic testing.

In people with MC, nerve conduction studies (NCS) are usually normal, while electromyography (EMG) shows characteristic signs of delayed muscle relaxation (myotonic discharges). A short exercise test (SET) often shows a brief drop in muscle response after exercise that improves with repeated movements and worsens with cold. Given that similar symptoms can occur in other muscle disorders, such as myotonic dystrophy or sodium channel myotonia, genetic testing is typically used to confirm the diagnosis.

Current management of MC

There are currently no FDA-approved treatments specifically for MC and management focuses on controlling symptoms. Appropriate neuromuscular care is critical in developing a tailored management plan for each affected person.

Some pharmacologic treatments are available to help reduce muscle stiffness and improve function. Sodium channel–blocking medications are the main treatment options. MC therapies include:

• Mexiletine, a sodium channel blocker approved in Europe
• Lamotrigine, a sodium channel blocker that may be used if mexiletine is not effective or tolerated
• Other sodium channel blockers such as ranolazine, carbamazepine, quinine, and phenytoin, which may help select patients
• Acetazolamide, which works by a different method and is an alternative to a sodium channel blocker

It is important to note that these medications can affect heart rhythm and liver or kidney function, so ongoing monitoring and care are essential.

Non-pharmacologic strategies are also important for managing MC. These may include avoiding exposure to cold, keeping muscles warm, using the warm-up phenomenon, and maintaining a regular, moderate exercise schedule. Paying attention to diet, hydration, and lifestyle factors can also help manage symptoms.

Evolving research and treatment landscape

Pre-clinical research into MC is progressing on a several fronts. Researchers continue to identify new MC-causing mutations within the CLCN1 gene. They are also working to figure out how these specific mutations disrupt chloride channels and cause MC symptoms. Other efforts are using induced animal models of MC to study pathways that lead to specific symptoms, such as pain, with the goal of testing future therapies in these models. These and other studies are helping to understand the genetic and physiologic mechanisms that contribute to MC.

Clinical development for MC is still in its infancy. Most current therapies for MC, including mexiletine, lamotrigine, and ranolazine, are used off-label, meaning they are not yet FDA-approved for this purpose. Clinical trials have been completed or are ongoing to confirm their efficacy in people with MC. Furthermore, some studies are exploring the use of exercise interventions to improve symptoms of MC.

To learn more about clinical trial opportunities in MC, visit clinicaltrials.gov and search for the specific disease name (e.g., “myotonia congenita”) in the condition or disease field.

MDA’s work to further cutting-edge IIM research

Since its inception, MDA has invested more than $2.5 million in MC research. Through strategic investments from MDA, partner advocacy groups, and the National Institutes of Health (NIH), MC research is slowly advancing. While new therapies remain a long-term goal, ongoing research efforts offer hope for meaningful advances and improved care for those living with this condition.

MDA’s Resource Center provides support, guidance, and resources for patients and families, including information about myotonia congenita (MC), open clinical trials, and other services. Contact the MDA Resource Center at 1-833-ASK-MDA1 or ResourceCenter@mdausa.org.