Becker Muscular Dystrophy

What is Becker Muscular Dystrophy?

Becker muscular dystrophy (BMD) is a genetic disorder passed down through families, caused by a mutation in a specific gene. The main symptom is muscle weakness that gets worse over time, especially in the lower body. People with this condition start showing symptoms at different ages, anywhere from 5 to 60 years old. According to a study of 67 BMD patients, most of them were able to walk on their own until their 40s or even later. Only a few lost the ability to walk at an earlier age. BMD symptoms generally show up later in life than those of a related condition known as Duchenne muscular dystrophy (DMD).

One way to tell the two conditions apart is based on when the patients need to use a wheelchair. For DMD, this usually happens before age 13, while people with BMD can often walk past the age of 16. However, identifying these conditions in patients who show muscle weakness before they turn 12 might require a genetic test.

BMD is seen more as a less severe version of DMD, rather than a separate condition by itself. As a result, trials to test new treatments are less frequently done for BMD compared to DMD.

Muscle cells, known as myocytes, are formed by the joining together of smaller cells during the early stages of body development. These myocytes have several nuclei and plenty of tiny, thread-like structures called microfilaments, which allow the myocytes to contract. The repeated pattern in myofibrils (the fibrous units inside myocytes) contains interwoven actin and myosin filaments with Z-bands arranged at right angles. The T-tubule system in the myocyte is where calcium is stored and released to help in contraction. Inside the myocyte, there are different substances like myoglobin, creatine, and lysosomes.

Actin combines with dystrophin, a protein located near the outer layer of the myocyte. Dystrophin connects to the matrix outside the cell via other proteins. It works to strengthen and stabilize the cell membrane. If there is something wrong with dystrophin, this is the main cause of BMD.

What Causes Becker Muscular Dystrophy?

Becker muscular dystrophy (BMD) is caused by a mutation in the dystrophin protein, which is located on the Xp21.2 chromosome. This issue tends to be inherited from parents and carried along the X chromosome. In some cases where there isn’t a clear link to X chromosomes, the problem might stem from the genes that code for proteins associated with dystrophin.

The dystrophin gene is located on the Xp21 region of the X chromosome and includes a massive 79 portions, or exons. Given its enormous size, with over 2 million base pairs (the building blocks of DNA), mutations can occur more frequently, especially during the creation of eggs or sperm. Other types of mutations, such as minor deletions, insertions, or changes in a few base pairs, occur, but they are less common.

It’s interesting how mutations differ between BMD and another disorder called Duchenne muscular dystrophy (DMD). DMD mainly happens when mutations disrupt the dystrophin gene in such a way that it can’t produce dystrophin at all. On the other hand, BMD results from mutations that allow some dystrophin to be produced, but it’s either not enough or it doesn’t work correctly. Therefore, symptoms of BMD can vary widely compared to DMD.

When scientists test the muscle tissue of those with these diseases, they see a complete lack of dystrophin in patients with DMD. However, individuals with BMD might have a little (10% to 40%) of the normal amount of dystrophin, or they might have a version that’s partially functional.

Risk Factors and Frequency for Becker Muscular Dystrophy

BMD, or Becker Muscular Dystrophy, is a rare disease that mainly affects males due to its transmission through the X chromosome. It is similar to but generally less severe than DMD, or Duchenne Muscular Dystrophy. Globally, both BMD and DMD affect between 0.1 to 1.8 out of every 10,000 male individuals. In 2010, a US study reported that 0.26 per 10,000 males were found to have BMD, and it seemed to be more common among white non-Hispanic males compared to black non-Hispanic males.

• The prevalence of BMD was found to be 0.01 per 10,000 males in South Africa.
• In Asia, it is between 0.1 to 0.2 per 10,000 males.
• In European countries, it ranges from 0.1 to 0.7 per 10,000 males.

While BMD is three times less common than DMD, it’s important to note that the condition may be underdiagnosed. Advances in genetic sequencing have helped us find more patients with BMD and also identify female carriers of the dystrophin gene mutation.

Signs and Symptoms of Becker Muscular Dystrophy

BMD, or Becker Muscular Dystrophy, is a condition that can show up in many different ways. It’s important to understand when and how the symptoms began, what makes them better or worse, which parts of the body are affected, and how serious the symptoms are. Any family history and the child’s developmental history should also be noted.

Children with BMD can show signs of muscle weakness in the upper parts of their limbs before the lower parts. They also tend to experience issues in their lower limbs before the upper ones. Kids may get muscle cramps during heavy physical activity and be late to reach certain physical development milestones. Slower growth and height, as well as intellectual difficulties, can also be signs of BMD. In some cases, roughly one in four patients may have an IQ of less than 70. A family history of BMD may also be identified.

In some people, BMD can develop later and they may be able to walk until they become adults. As BMD advances, it can lead to issues like elbow fractures, heart disease, breathing difficulties, stiff joints, and a walking style where the person walks on their toes. The heart condition, known as cardiomyopathy, can lead to dangerous irregular heartbeats because of scarring in the wall of the heart’s left ventricle.

Some unusual signs of BMD can include high levels of a substance called CK in the blood, but no weakness, or nervous system symptoms rather than muscular ones. Female carriers of BMD may primarily have heart disease, though some could also have slight muscle weakness. About 22% of carriers show symptoms, with a great deal of variability. A genetic test is required for an accurate diagnosis.

A physical check-up for BMD may show the following:

• Shrinking of muscles, particularly the calf muscles, which can seem larger due to fibrous and fatty tissues filling in for the lost muscle (muscle pseudohypertrophy)
• Decreased muscle strength, reflexes, and muscular tremors in the thigh muscles (quadriceps)
• Needing to use the hands and arms to stand up from a squatting position (Gowers sign)
• A curve in the lower back (lumbar lordosis)
• Shrunken Achilles tendons
• Stiffness in the knee, elbow, or hip joints
• An enlarged tongue
• Increased muscle size in the forearms
• A curved spine due to weakening muscles in the chest
• Signs of heart problems such as neck veins bulging, the point where the heart pumps moving, swelling in the limbs, a kind of ‘galloping’ heartbeat, and heart murmurs

In serious cases, signs of respiratory failure such as crackling sounds, bluish skin, and low oxygen levels can be observed. Everyone suspected of having BMD should undergo detailed examinations of their head, neck, musculature, and nervous system. As these patients are at a higher risk of heart and respiratory failure, they should also have complete cardiovascular and respiratory exams during every check-up.

Testing for Becker Muscular Dystrophy

If a man exhibits weakness in the muscles of the upper body and enlargement in the lower body, doctors would suspect Becker Muscular Dystrophy (BMD), particularly if there’s a family history of the condition. To confirm a BMD diagnosis, doctors typically look at CK levels and conduct a dystrophin gene deletion analysis or a muscle biopsy with dystrophin antibody staining. However, since a muscle biopsy is quite invasive, it is often avoided, and genetic testing is usually enough for confirmation.

CK Levels:
CK levels in the blood can indicate if muscle damage is occurring. These levels usually peak when someone is between the ages of 10 to 15. If someone’s creatinine levels are also more than five times the normal level, that’s another sign of muscle degradation.

Genetic Analysis:
Genetic analysis has become the preferred method of diagnosis since it can identify deletions and duplications through tests like multiplex ligation-dependent probe amplification, fluorescence in situ hybridization, and polymerase chain reaction. Of these, multiplex ligation-dependent probe amplification is the one most commonly used for diagnosis. Muscle biopsy with dystrophin antibody staining may be used if the genetic analysis results come back negative.

Genetic analysis is usually the first step in diagnosing patients with no known family history of the disorder. By contrast, for patients who have a family history of the disease, the diagnosis is simple because the gene mutation is already known.

Electromyography:
This test might be used to tell the difference between disease processes originating in the nerves or the muscles. It can also guide doctors to the best muscle group to biopsy. But electromyography isn’t often used for BMD diagnosis.

Muscle Magnetic Resonance Imaging:
Muscle MRI scans can be useful in diagnosing and tracking the progression of all dystrophinopathies (issues with the dystrophin protein). MRIs are useful for visualizing fat infiltration, muscle loss, swelling from muscle damage, and scar tissue without needing surgery. The pattern of which muscles are affected can offer insight into different types of muscle diseases.

Muscle Biopsy:
If a muscle biopsy is taken, doctors will look for signs of muscle cell death and regeneration, fatty tissues replacing muscle, and scar tissue within the muscles. But these are not specific to BMD, and genetic testing is still the preferred method of confirming the diagnosis.

Electrocardiography:
People with BMD are more likely to have heart disease, so electrocardiography tests are a good way to evaluate heart function in people affected by the condition. This method can detect irregular heart rhythms early on in patients showing symptoms.

Other Tests:
There are a few other tests that might be performed, depending on how the patient presents. Blood tests might reveal higher transaminases if muscle damage is occurring. Pulmonary function tests might be needed since BMD can affect the muscles involved in breathing. And if the muscles in the trunk of the body are becoming weak, spinal x-rays can be used to monitor the progression of scoliosis. However, these tests are not necessary for diagnosing BMD.

Treatment Options for Becker Muscular Dystrophy

Becker Muscular Dystrophy (BMD) currently has no cure. Scientists are exploring gene therapy to restore normal levels of a protein called dystrophin, which is critical in muscle functions. Yet, these clinical trials are still ongoing. Right now, the main treatments for BMD involve supportive care and rehabilitation.

Medication is often used to help manage the muscle weakness associated with BMD. Although no specific treatment is officially approved for BMD, the strategy is usually akin to those implemented for mild cases of Duchenne Muscular Dystrophy (DMD), another muscular disease. Corticosteroids, such as Prednisolone or Deflazacort, are often prescribed. These medications are started before the patient becomes physically disabled and should continue even after a patient has lost the ability to walk.

These drugs not only reduce muscle weakness but also delay heart disease, improve lung function and slow down the development of a spine curvature known as scoliosis, reducing the need for surgery. If a patient experiences side effects, the dose may be lowered. In some cases, nitric oxide is also suggested to enhance muscle circulation.

BMD often comes with heart complications, a major health risk for individuals with this condition. Early treatment of these cardiovascular issues is key, and typically involves medications such as angiotensin-converting enzyme inhibitors and β-blockers.

Rehabilitation therapies are essential and cover different aspects of the patient’s life, involving physical, speech, occupational, and recreational therapy. These therapies aim to maintain muscle function and overall health for as long as possible.

Sometimes, progressive muscle weakness can lead to scoliosis and joint contractions. Here, careful monitoring and physical therapy may help those with slowly worsening symptoms. Surgery could be considered for patients with rapidly progressing symptoms to preserve their mobility.

If respiratory failure occurs, a combination of treatments may be implemented. This may include tracheostomy (making an incision in the windpipe for assisted breathing), assisted ventilation, and heart disease medication. For patients with BMD, using a ventilator at home can help to reduce pressure on the lungs and protect the heart, particularly when these mechanical devices are incorporated with heart-protective medication.

For children with BMD, the disease can also affect their growth and delay puberty. In these cases, consulting an endocrinologist can be beneficial. Doctors may prescribe a low dose of testosterone to promote normal bone growth and prevent osteoporosis.

New treatments are continually being explored – for instance, a synthetic drug named vamorolone that acts similarly to glucocorticoids has shown promise in early trials for its potential anti-inflammatory effects. However, more trials are needed to fully support its use in managing BMD.

What else can Becker Muscular Dystrophy be?

Becker muscular dystrophy (BMD), a medical condition characterized by muscle weakness, needs to be differentiated from other similar conditions. Some of these include:

• Duchenne muscular dystrophy (DMD): More serious and starts earlier than BMD; patients may be forced to use wheelchairs earlier and typically show a significant reduction in dystrophin, a vital protein for muscle fibers.
• Polymyositis: This is an inflammation of the muscles, but unlike BMD, it doesn’t present with swelling in the distal muscles (the muscles farthest from the center of the body).
• Spinal muscular atrophy: This can be identical to BMD, but some signals like weak reflexes, twitching tongue, weakness in muscles controlled by the brain stem or nerve cell cluster in the brain, less frequent cognitive impairment might point towards this condition in cases where no mutation in the dystrophin gene is found.
• Limb-girdle muscular dystrophy: Can present symptoms similar to BMD without any swelling in calf muscles.
• Dilated cardiomyopathy: This heart muscle condition might appear as BMD but can result from causes other than muscular dystrophy.
• Emery-Dreyfuss muscular dystrophy: Unlike BMD, this condition features early contractures (shortening of muscles that results in deformity) and heart defects and is recognizable by weakness and decreased muscle mass in the shoulder and lower leg muscles.
• Myasthenia gravis: This can be confused with BMD as it also causes variable muscle weakness, but symptoms such as facial weakness, droopy eyelids, and double vision are not observed in BMD.
• Metabolic myopathies: Metabolic disorders including those arising from abnormalities in the processing of fats or sugars in the body can lead to general muscle weakness. However, most patients with these conditions show symptoms like liver enlargement, decreased muscle tone, and low blood sugar, often as early as infancy. When they reach adolescence or adulthood, they might experience fatigue in their muscles when they exercise.

An in-depth health assessment and suitable diagnostic tests can help differentiate BMD from these similar conditions.

What to expect with Becker Muscular Dystrophy

Becker muscular dystrophy (BMD) usually has a less severe impact compared to Duchenne muscular dystrophy (DMD). That said, as the disease advances, the likelihood of survival declines. Patients increasingly need assistance to extend their life span. People with BMD generally live until around 40 to 50 years. The most common cause of death is an enlarged heart, also known as dilated cardiomyopathy.

Possible Complications When Diagnosed with Becker Muscular Dystrophy

BMD, or Becker Muscular Dystrophy, can unfortunately lead to many potential complications. These include:

• Difficulty in walking or moving properly
• Problems with memory and thinking
• Impaired growth
• Broken bones
• Heart muscle diseases
• Tight joints
• Curving of the spine
• Chest infections after surgery
• Failing liver and lung functions
• Kidney failure due to breakdown and leakage of muscle contents into the blood
• Suppressed immunity and adrenal gland problems from prolonged corticosteroid use

However, seeking early and comprehensive medical care can help manage these symptoms and significantly improve the quality of life for those affected by BMD.

Preventing Becker Muscular Dystrophy

It’s crucial for families that have a known issue with the dystrophin gene to receive genetic counseling. Women who carry this gene should be made aware of the choices they have regarding family planning. Those affected, and their families, should be clearly informed about how the gene is passed down to help them understand how BMD, or Becker Muscular Dystrophy, can be inherited.

Treatments for BMD are not beneficial if started late. Therefore, patients and their families need to be educated about how the disease progresses. They should also be encouraged to stay in close contact with their doctors and specialists for rehabilitation. If a person with BMD has any new symptoms, they should seek medical attention right away.

It’s also important for patients and their families to understand the different treatments and diagnostic tests available for BMD. Before starting any treatments, patients need to know about the potential side effects, especially if they’re taking corticosteroids for a long time. The symptoms of toxicity from corticosteroids should be explained to those affected and their families. They should be encouraged to get help immediately if they notice these symptoms. Finally, patients should be given honest information about what they can expect in terms of the disease’s progression.