Rippling Muscle Disease

What is rippling muscle disease?

Rippling muscle disease (RMD) is a rare neuromuscular disorder that involves repetitive muscle contractions, muscle stiffness and increased muscle volume (hypertrophy).

Symptoms of rippling muscle disease most often begin in late childhood or adolescence. But it can begin at any age.

What are the symptoms of rippling muscle disease?

As its name suggests, symptoms of rippling muscle disease (RMD) mainly affect your muscles — your skeletal muscles. RMD tends to affect the muscles near the center of your body (proximal muscles) the most, especially your thigh muscles (quadriceps).

If you have RMD, it means your muscles are “irritable” or “excitable” — they’re unusually sensitive to movement or pressure.

The symptoms that are always present in RMD include muscle mounding (when your muscle “bunches up”) and repetitive muscle tensing (contractions) that can last up to 30 seconds. These symptoms typically happen when your muscle experiences a sudden impact, like if you bump into something.

About 60% of people with RMD have visible muscle rippling (wave-like contractions that might look like worms crawling under your skin) that last fi to 20 seconds. This typically happens when you stretch a muscle.

Other symptoms include:

• Fatigue.
• Muscle cramps.
• Muscle stiffness.

These symptoms are more likely to happen after strenuous exercise or with exposure to cold temperatures.

Some people with RMD may have hypertrophy (muscle overgrowth) of certain muscles and an atypical gait (walking pattern).

Is rippling muscle disease painful?

Rippling muscle disease can cause muscle pain when you experience repetitive muscle contractions, especially if they last a while. RMD can also cause muscle cramping, which can be painful.

What causes rippling muscle disease?

Most cases of rippling muscle disease result from mutations (changes) in the CAV3 gene that you inherit from a biological parent. This gene provides instructions for your body to make a protein called caveolin-3, which is in the membrane surrounding muscle cells. This protein may also help regulate calcium levels in muscle cells, which play a role in muscle contraction and relaxation.

In RMD, the CAV3 mutation results in a lack of caveolin-3 protein. Researchers think that this shortage affects the normal control of calcium levels in muscle cells, leading to abnormal muscle contractions as a result of pressure or stretching.

There are multiple types of CAV3 gene mutations. Muscle conditions that result from these mutations are called caveolinopathies. Along with RMD, they include:

• Autosomal dominant limb-girdle muscular dystrophy (formerly classified as LGMD1C).
• Hypertrophic cardiomyopathy.
• Isolated hyperCKemia.
• CAV3-related distal myopathy.

These conditions may sometimes share symptoms of RMD, like wave-like muscle contractions.

There have also been reported cases of an autoimmune form of rippling muscle disease that happens alongside myasthenia gravis. People with this form of RMD don’t have CAV3 mutations.

How do you inherit rippling muscle disease?

In most cases, people inherit rippling muscle disease in an autosomal dominant pattern. This means that you inherit one copy of an altered CAV3 gene from one biological parent.

In some cases, people may inherit RMD in an autosomal recessive pattern. This means that you inherit a copy of an altered CAV3 gene from both biological parents.

People with autosomal recessive rippling muscle disease typically have more severe symptoms than people with the autosomal dominant form.

In rare cases, RMD can result from new mutations (not inherited from parents). This can happen to people with no family history of RMD or other caveolinopathies.

How is rippling muscle disease diagnosed?

Healthcare providers use the following exams and tests to diagnose rippling muscle disease, though all of them aren’t always necessary:

• Medical history, especially family history of RMD or other caveolinopathies.
• Physical and neurological exams.
• Creatine kinase blood test.
• Electromyography (EMG).
• Muscle biopsy.
• Antibody tests to check if RMD is autoimmune.
• Genetic testing to look for a CAV3 gene mutation.

These tests can help rule out other conditions with similar symptoms and/or confirm a rippling muscle disease diagnosis.

During the diagnostic process, your provider may refer you to a specialist, like a neurologist who specializes in neuromuscular disorders or a geneticist.

What is the treatment for rippling muscle disease?

Treatment for rippling muscle disease depends on whether it’s the genetic or autoimmune form.

Treatment for the genetic form mainly involves symptom management and referral for genetic counseling. Certain medications can help if muscle cramps or contractions are severe. Medications may include:

• Dantrolene, a muscle relaxant.
• Calcium channel antagonists.
• Benzodiazepines.

Treatment for the autoimmune form of RMD may involve immunosuppressive therapy and/or thymectomy (removal of your thymus gland) if you have a thymoma (tumor).

Can I prevent rippling muscle disease?

As most cases of rippling muscle disease are genetic, there’s nothing you can do to prevent it.

If you’re concerned about the risk of passing on RMD or other genetic conditions before trying to have a biological child, talk to your healthcare provider about genetic counseling.

When should I see my healthcare provider about rippling muscle disease?

If your RMD symptoms become more severe or more frequent, talk to your healthcare provider.

If a biological family member has recently received a rippling muscle disease diagnosis, talk to your provider if you or other family members are at risk for developing the condition.

What questions should I ask my healthcare provider?

It may be helpful to ask your healthcare provider the following questions:

• What can I do to manage my symptoms?
• What treatment is best for me?
• Could I pass rippling muscle disease onto my biological children?
• Should my biological family members get tested for rippling muscle disease?

Does rippling muscle disease affect the heart?

Rippling muscle disease itself doesn’t affect your heart. However, RMD is related to hypertrophic cardiomyopathy (a heart condition) because they both involve mutations of the same gene. It’s possible to have CAV3 gene mutations that affect both your heart muscles and skeletal muscles, but this is very rare.

Is rippling muscle disease fatal?

Rippling muscle disease itself isn’t fatal. But symptoms of RMD, like wave-like muscle contractions, can be features of other conditions that involve CAV3 gene mutations (caveolinopathies).

Severe cases of two of these conditions — autosomal dominant limb-girdle muscular dystrophy and hypertrophic cardiomyopathy — may be life-threatening.