Muscular Dystrophy

What is Muscular Dystrophy?

Muscular dystrophy refers to a set of inherited diseases that cause muscles to become progressively weaker and smaller over time. It affects about 1 in every 5,000 people across the world and can appear at any age, although it’s typically found during childhood. The main cause of this condition are changes, or mutations, in the genes that are responsible for the structure and function of muscles. These changes result in the gradual break down and loss of muscle fibres.

“Muscular dystrophy” is a broad term that covers a range of inherited disorders which lead to a gradual, widespread muscle disease. This results from an insufficient amount or, in some cases, absence of glycoproteins, a type of protein sugar, in the cell, surrounding or ‘plasma’ membrane of the muscle. Muscular dystrophy isn’t contagious and has different variations, each with unique patterns of how it’s inherited, when symptoms start, and the rate at which muscle decay happens. Specific changes or alterations in particular genes cause different forms of this disease.

Muscular dystrophy impacts the muscles that support the body (skeletal muscles) and the heart (cardiac muscles). How the condition progresses depends on the particular type and severity of the disease, but generally, there is a pattern of growing muscle weakness, decreased ability to move, and chances of developing complications related to breathing and heart function.

What Causes Muscular Dystrophy?

Muscular dystrophy is a group of genetic diseases that lead to muscle weakness and loss. This happens because of changes, or mutations, in various genes. These genes then fail in their normal functioning – they are no longer effective in helping produce certain proteins needed for our bodies to build and maintain healthy muscles.

The most common cause of muscular dystrophy is a mutation in a gene called DMD, which is responsible for the creation of a protein known as dystrophin. This mutation usually occurs in males, as they possess only one copy of the X chromosome that carries this gene. Depending on the impact of the mutation and the level of dystrophin deficiency, it can lead to either Duchenne or Becker muscular dystrophy, two forms of the disease that differ in severity.

Other types of muscular dystrophy can occur due to defects or lack of certain glycoproteins, a type of protein in our body. The dystrophin gene, specifically, is enormous (with 79 segments of coding DNA called exons), which makes it more likely to randomly mutate or develop defects.

Lack of dystrophin protein causes damage to our muscles, leading to their weakening and eventual death. This process can affect muscles throughout our body, causing a variety of symptoms and problems.

However, the way in which these mutations affect muscles is similar across all types of the disease. Early diagnosis, genetic testing, and proper treatment can help manage symptoms and improve the quality of life for those living with muscular dystrophy.

Muscular dystrophy can be inherited in a number of ways, with different types displaying different inheritance patterns. For instance, Emery-Dreifuss muscular dystrophy can result from different mutations on various chromosomes. Similarly, Limb-Girdle Muscular Dystrophy can have different causes and presents with varying severity based on its cause. Depending on the specific type, the pattern of muscle weakness and age of onset can also vary widely.

Similarly, other subtypes of muscular dystrophy such as Facioscapulohumeral, Myotonic, and Oculopharyngeal occur due to different gene mutations and follow differing inheritance patterns. Congenital muscular dystrophy is caused by a recessive gene mutation and Becker and Duchenne muscular dystrophy are caused by mutations on the X chromosome.

Of note, Duchenne muscular dystrophy can sometimes even occur in females due to defects in how their X chromosomes function. Despite the wide variety in the causes and types of muscular dystrophy, the common factor is the degeneration of muscles due to genetic abnormalities. In all cases, early diagnosis and appropriate management can significantly improve the quality of life for those affected.

Risk Factors and Frequency for Muscular Dystrophy

Muscular dystrophy is a relatively rare disease that impacts about 1 in 5,000 to 10,000 people worldwide. In the United States, it’s estimated that around 250,000 individuals are living with muscular dystrophy or a similar neuromuscular disorder. The disease’s prevalence can be tricky to estimate because it varies widely in terms of how severe it is, when it starts, and the complex genetic testing needed for diagnosis. It’s also important to realize that the prevalence changes based on the specific type of muscular dystrophy and the characteristics of the population studied.

• Duchenne muscular dystrophy is the most common type of muscular dystrophy in children, affecting about 1 in every 3,500 to 5,000 male births globally. It mostly affects boys and typically starts between the ages of 3 to 5. It’s a progressive disease that usually results in death by late teens or early 20s.
• Becker muscular dystrophy is a less severe form of the disease caused by mutations in the same gene as Duchenne muscular dystrophy. This condition affects about 1 in 18,000 to 30,000 individuals worldwide, primarily males. Becker muscular dystrophy generally starts later and progresses slower than Duchenne muscular dystrophy, with individuals often able to walk into adulthood.
• Limb-girdle muscular dystrophy is a group of inherited muscular dystrophies that mainly affect the hip and shoulder muscles. There are over 30 subtypes, each caused by gene mutations. The prevalence of Limb-girdle muscular dystrophy varies based on the specific subtype, with estimates ranging from 1 in 14,500 to 123,000 people worldwide.
• Facioscapulohumeral muscular dystrophy impacts approximately 1 in every 20,000 individuals worldwide. This type of muscular dystrophy typically starts later and progresses more slowly than other types, with symptoms in the teen or adult years. It’s caused by mutations in the DUX4 gene.

While muscular dystrophy affects more males than females due to many related genetic mutations appearing on the X chromosome, some forms like limb-girdle muscular dystrophy affect both genders equally. However, the prevalence of certain types of muscular dystrophy can vary greatly:

• General population prevalence of muscular dystrophy: 16 to 25.1 per 100,000 individuals.
• Frequency of muscular dystrophy in the general population: 1 per 3,000 to 8,000 individuals.
• Incidence of muscular dystrophy in male births: 1 per 5,000 or 200 per 1,000,000.
• Prevalence of Becker muscular dystrophy in the general population: 4.78 per 100,000 individuals.
• Frequency of Becker muscular dystrophy in live male births: 1 per 18,000.
• Prevalence of Duchenne muscular dystrophy in the general population: 4.78 per 100,000 individuals.
• Frequency of Duchenne muscular dystrophy in males: 1 per 3,500.
• Prevalence of Facioscapulohumeral muscular dystrophy in the general population: 3.95 per 100,000 individuals.
• Prevalence of Limb-Girdle muscular dystrophy in the general population: 1.63 per 100,000 individuals.

These prevalence rates apply mostly to the US, England, Australia, and Canada unless stated otherwise.

Signs and Symptoms of Muscular Dystrophy

Muscular dystrophy is typically diagnosed between one’s 30s and 40s. However, it might manifest during infancy or progress quickly from the beginning. The first sign mothers and fathers notice is typically a difficulty with their kid’s ability to walk when compared to similarly aged children. Kids may have trouble with tasks such as kicking a ball because of muscle weakness. Sometimes, both parents may seem perfectly healthy.

During a physical examination, doctors will often note several signs in people affected by muscular dystrophy. Their calf muscles may appear unusually large, and they might show weakness in the primary muscles of their lower limbs. As such, they often require their arms and hands to help them when getting up from sitting. Other signs include a history of delayed walking, toe walking, enlarged calf muscles, and instability in the hip girdle muscles.

There are also other less typical presentations of muscular dystrophy. These include asymptomatic high levels of serum creatine kinase (CK), intolerance to exertion, dilated cardiomyopathy, malignant hyperthermia, quadriceps myopathy, language delay, and in some rare cases, Turner syndrome in X chromosome monozygotic females with Duchenne muscular dystrophy. Some individuals with subclinical muscular dystrophy may be diagnosed based on family history or high liver enzyme levels. Typically, males are the ones that get affected by muscular dystrophy.

Muscular dystrophy can affect the heart muscle, leading to arrhythmias and heart block. It can also cause congestive heart failure and dilated cardiomyopathy. These cardiovascular conditions are often associated with muscular dystrophy.

Muscular dystrophy patients often experience muscle wasting, difficulty walking, and exhibit deformities in different parts of their body. It may aggravate spinal deformities leading to conditions such as lordosis or scoliosis, and may lead to eye issues like cataracts and bilateral ptosis.

Most patients of muscular dystrophy experience some degree of joint contractures affecting the elbows, knees, hips, and ankles. It could lead to muscular atrophy, skeletal deformities, and progressive scoliosis often associated with pain.

Children suffering from Duchenne muscular dystrophy often show slow development of motor skills. They can be clumsy, fall frequently, and face difficulty climbing stairs. For these children, the usage of a wheelchair becomes inevitable by the age of 12.

Another notable feature of muscular dystrophy from a young age is the inability to close the eyes completely. This gives their face a drooping expression. Other typical signs of muscular dystrophy include muscle weakness and inactivity, which could lead to osteoporosis and an increased chance of fractures. Bisphosphonates may be considered as a treatment to enhance bone strength.

Another thing to note is that patients with muscular dystrophy may experience an excessive urge to sleep and daytime drowsiness. It’s also common for them to have sleep-related problems. All these could add to fatigue and hamper daily activities. Respiratory failure is also common in patients suffering from muscular dystrophy. Also, patients can experience difficulty swallowing due to the involvement of esophageal muscles.

In myotonic dystrophy patients, the esophageal muscles may also be involved, leading to issues swallowing. In individuals with muscular dystrophy, malabsorption, cramping pain, and other digestive problems may be experienced. This could also lead to constipation and, in severe cases, aspiration of food and acute gastric dilation, which can be causes of death. Speech and swallowing difficulties might also be noticed due to the involvement of the tongue, pharyngeal, and palatal muscles. More significant issues could lurk, as muscular dystrophy patients may also demonstrate challenges with glucose metabolism, thus increasing their risk of developing diabetes.

Testing for Muscular Dystrophy

Tests for Muscular Dystrophy

When a doctor wants to determine if a patient has muscular dystrophy, they will consider many factors such as the patient’s symptoms, medical history, and the type of muscular dystrophy they suspect the patient may have. Several tests are often needed to make a certain diagnosis and decide on the best treatment plan.

Laboratory Tests

Liver Enzymes Tests: These measures the levels of liver enzymes (like ALT and AST) in your blood. High levels could indicate muscular dystrophy.

Aldolase Test: This tests for aldolase, a certain type of enzyme in your blood. High levels could indicate the presence of muscular dystrophy, though the levels may decrease as the disease progresses.

Arterial Blood Gas Test: This measures the levels of oxygen and carbon dioxide in your blood. If your breathing muscles aren’t working properly (which can happen with muscular dystrophy), it can lead to respiratory acidosis, a condition where there’s too much carbon dioxide in your bloodstream.

Creatine Phosphokinase (CPK) Test: High levels of CPK, which is an enzyme found in your heart, brain, and muscles, is a sign of muscular dystrophy.

Urinalysis: With a urinalysis, your doctor checks for sugar and a protein called myoglobin in your urine. Having sugar in your urine could indicate diabetes, a common health problem in people with muscular dystrophy.

Imaging Tests

Some imaging tests may also help in diagnosing muscular dystrophy:

Magnetic Resonance Imaging (MRI): An MRI can reveal characteristic elements of muscular dystrophy. It can show if certain muscles have an excessive amount of fat, or whether some bones in the foot have a particular type of deformity, among other things.

Computed Tomography (CT) Scan: A CT scan can provide detailed images of your muscles, showing whether they have atrophied (become smaller) or if the muscle tissue has been replaced by fat.

Other Tests

Genetic Testing: To confirm the diagnosis of muscular dystrophy, you may have a blood test to check for mutations in your genes.

Immunocytochemistry: This test uses special dyes to check for certain proteins in your muscle tissue. The presence, absence, or deficiency of these proteins can help diagnose muscular dystrophy.

Muscle Biopsy: In this test, a small piece of muscle tissue is removed and examined under a microscope. It can show whether your muscle fibers are normal or not.

Electrocardiogram (ECG): This test is used to measure the electrical activity of your heart. It can help detect heart problems that are common in people with some types of muscular dystrophy.

Western Blot: This test analyzes protein in muscle tissue to identify abnormalities.

Polysomnogram: This sleep study is used to identify sleep issues, which are not uncommon in people with muscular dystrophy.

Pulmonary Function Tests: These tests measure how well your lungs are working, which can be affected by muscular dystrophy.

In all cases, these tests will make it easier for your doctor to formulate the right treatment strategy if muscular dystrophy is diagnosed.

Treatment Options for Muscular Dystrophy

Treatment for muscular dystrophy is centered around managing symptoms, slowing the progression of the disease, and helping those affected to lead a better life. As of now, there’s no cure for the condition, but various approaches exist to tackle specific challenges like muscle weakness, mobility issues, and potential complications.

This usually involves a mix of physical therapy, assistive devices, medications and in some cases, surgery.

Medication

Medication plays a key role in treating the heart-related issues that muscular dystrophy can cause. Doctors often prescribe angiotensin-converting enzyme (ACE) inhibitors and specific medicines known as antiarrhythmics for those experiencing heart rhythm problems. Certain other drugs like flecainide, propafenone, and beta-blockers are given in cases of abnormalities in heart rhythm.

Another symptom associated with muscular dystrophy, myotonia or muscle stiffness, can be managed with medications known as sodium channel blockers. These include phenytoin, procainamide, or mexiletine. However, as these medications can cause side effects, they are typically chosen based on the patient’s individual needs and health history.

Similarly, steroids, specifically glucocorticoids like prednisone, have been found to slow the progression of muscular dystrophy for up to 3 years. While possible side effects include weight gain and an increased risk of fractures, there’s evidence to suggest that early use of these steroids can lead to significantly improved outcomes, like enabling children to walk for longer and increasing life expectancy. Further research is needed to confirm their effectiveness in treating all types of muscular dystrophy.

Other types of medication such as antiepileptics and nonsteroidal anti-inflammatory drugs (NSAIDs) are also used to treat symptoms related to muscular dystrophy. Antiepileptics are effective in controlling seizures in some individuals, while NSAIDs help reduce pain and inflammation.

Golodirsen (SRP-4053), a treatment specifically designed for Duchenne muscular dystrophy, has been approved by the FDA. But the evidence supporting its wide usage is still being established.

Surgery

In certain cases, surgery may be used to manage the various aspects of muscular dystrophy. For instance, procedures to release contractures (tightness or shortening of muscles) can help maintain normal function for as long as possible. When the disease begins to affect the heart, a defibrillator or cardiac pacemaker may be implanted to monitor and manage heart disease and irregular heart rhythms. Surgery can also help stabilize the shoulder in certain types of muscular dystrophy or correct the spine in cases of scoliosis, helping to prolong respiratory function and/or walking ability.

Other Interventions

In addition to medications and possible surgical options, supportive care is essential. Physical therapy can help prevent contractures and prolong the ability to walk. Strenuous exercise is done mindfully, taking into account the potential effect on muscle health.

Bracing can also help support normal functioning for as long as possible. A good wheelchair, ankle-foot orthoses (braces), and other assistive devices are often crucial to those with muscular dystrophy. In those who experience foot drop, plastic ankle-foot orthoses can help maintain mobility for a longer duration. Wheelchairs can be used for longer distances when required.

Besides physical treatment, psychological support is equally important to help handle the mental and emotional aspects of the condition. Genetic counseling is also recommended, especially for conditions passed through the X-chromosome. If the affected individual has children, all their daughters will be carriers of this X-linked recessive disorder.

Last but not least, radiation therapy might be an option in managing specific symptoms and complications of muscular dystrophy. However, it needs careful consideration and more research is needed to understand its potential benefits and risks.

What else can Muscular Dystrophy be?

Diagnosing muscular dystrophy may not be simple and can possibly be confused with other conditions that have similar causes. Doctors need to consider and rule out the following conditions, which may also cause muscular disorders and can lead to serious health issues:

• Adrenal insufficiency
• Electrolyte imbalance: mainly sodium, potassium, and magnesium
• High levels of calcium in blood (hypercalcemia)
• Porphyrias (rare group of genetic disorders)
• Rabies
• Severe migraine
• Temporary weakness after a seizure (Postictal/Todd paralysis)
• Low blood sugar (Hypoglycemia)
• A sudden condition causing muscle weakness in the lower body (Acute spastic paraparesis) – which is a medical emergency
• Myasthenia gravis
• Pancoast tumor
• Paraneoplastic syndromes (a group of rare disorders)

An acute onset gait disorder, or walking difficulty, often suggests severe health issues. A detailed evaluation is critical to exclude serious conditions. A gait disorder should not be attributed to a single disease. More serious conditions may be indicated by gait problems, especially if associated with the following symptoms:

• Headache
• Nausea or vomiting
• Decreased alertness
• Lack of coordination on one side of the body
• Recent viral illness/vaccination (Guillain-Barré syndrome)
• Physical injury (Trauma)

When dealing with a patient presenting these symptoms, doctors should consider the following:

• Are the reflexes weak?
• Is there any pain?
• Is the problem acute (short-term) or chronic (long-term)?
• Is the weakness mainly in the distant parts of the body or closer to the center?
• Is the muscle weakness widespread or localized to a specific area?
• Are there any signs of localized neurological problems, such as drooping of the upper eyelid?

What to expect with Muscular Dystrophy

People with certain types of muscle diseases that heavily affect the heart can still live relatively long lives if their heart problems are closely watched and treated aggressively. The main goal of long-term care is to keep people walking and on the lookout for any signs of heart or lung complications. Unfortunately, despite advancements in treatment for muscle diseases, these conditions remain incurable and lack preventative treatment. Typically, most patients pass away from heart and lung failure before they turn 30. However, proper care can significantly improve life quality for those affected.

Duchenne muscular dystrophy often results in a life expectancy of around 20 years, with no survivors to date. Children with Duchenne muscular dystrophy usually pass away due to lung or heart problems, typically in their late teens. Only 25% live to age 21. Walker-Warburg Syndrome, the most severe type of muscle disease present at birth, usually results in death by the age of 1. On the other hand, Becker dystrophy shortens life expectancy, but most people tend to live into their 40s or 50s. For people with facioscapulohumeral dystrophy, life expectancy is usually average.

Possible Complications When Diagnosed with Muscular Dystrophy

Muscular dystrophy, a disease that weakens and breaks down your body’s muscles, can cause a few complications:

• Bone loss: Being unable to move around or being bedridden may lead to weaker and thinner bones (referred to as osteopenia and osteoporosis). This increases the risk of broken bones and the development of a curved spine, or scoliosis.
• Heart and lung disease: It’s important to regularly check on individuals with muscular dystrophy, as the condition may lead to other health problems. These can include heart and lung diseases, or heart failure due to a weakened heart muscle (known as cardiomyopathy).
• Disability: Injuries to the muscles and stiff, rigid joints (called contractures) can result in disability. Individuals might need help moving around, such as using a wheelchair.
• Risks with anesthesia: People with muscular dystrophy might face difficulties with general anesthesia — the medicine that puts you to sleep for surgery. They usually need careful monitoring after surgery to make sure they recover properly.

Preventing Muscular Dystrophy

People with muscular dystrophy should know that care and prevention come together in a thorough approach designed to avoid complications and boost overall health. Key things that can help include the right types of physical activity and routine visits to the orthopedic doctor to manage the spine curvature condition known as scoliosis. Additionally, monitoring heart and lung health, getting proper nutritional advice, taking care of respiratory needs, following guidelines to prevent falls, learning about the genetic aspects of the condition, and understanding how to manage medications can all positively influence overall well-being.

Having emotional support is also important, and that can come from joining support groups and using counseling services. It’s also vital to have routine medical check-ups and honest conversations with healthcare providers. The ongoing checks and addressing worries as they come up, allows people to play an active role in their care and make improvements to their quality of life.