Muscular dystrophy

Muscular dystrophy is characterized by its progressive nature, which means it constantly worsens over time. Initially, it targets a specific set of muscles, such as those of the face, legs, arms, spine, or even the heart. Eventually, it will begin to affect muscles across a wider spectrum.

Providing care for patients diagnosed with this condition is complex and ongoing. Although there is no known cure for this disease, there are a number of therapeutic methods that have the ability to improve quality of life.

What is muscular dystrophy?

The occurrence of certain genetic mutations on the X chromosome is the main cause of muscular dystrophy. Each variant of this disease results from a distinct mutation, but all these chromosomal abnormalities culminate in preventing the production of dystrophin. This protein plays a crucial role in the development and healing of muscle tissue.

Proper functioning of muscle tissue depends on a network of proteins, among which dystrophin plays an essential role. Dystrophin's task is to draw various elements from muscle cells and anchor them to the sarcolemma, or the outer membrane of the muscle.

If the dystrophin protein is defective or completely absent, this inhibits the natural course of a biological process, resulting in faulty functioning of the outer membrane. This defect, in turn, leads to a gradual deterioration of muscle strength.

Duchenne muscular dystrophy is a specific example of a case in which dystrophin is largely absent. The symptoms of the disease tend to worsen as dystrophin production decreases.

Types of muscular dystrophy

Duchenne muscular dystrophy

Gradual muscle weakening is a hallmark of Duchenne muscular dystrophy, a degenerative muscle disease. This weakness is caused by inadequate levels of the protein known as dystrophin.

The condition is congenital, meaning it is present at birth. However, it is possible for symptoms to go unnoticed until later. This can be attributed either to a newly developed genetic mutation or to the condition being transmitted through the X chromosome.

Becker muscular dystrophy

Becker muscular dystrophy is a medical condition that causes gradual muscle weakening. The main cause of this weakening is insufficient production of the specific protein called dystrophin.

The clinical manifestations of this disorder are less severe compared to Duchenne muscular dystrophy, which it resembles.

Limb-girdle muscular dystrophy

Limb-girdle muscular dystrophy is a group of different diseases that result in the inability of the limb muscles to remain strong and healthy. The areas of the body most affected by these disorders are the proximal muscles, or those closest to the central area of the body. These proximal muscles include the shoulders, arms, thighs, and pelvic region.

Other types and the differences between them

Myotonic dystrophy

Myotonic dystrophy, commonly known as Steinert's disease, is characterized by myotonia, which is the inability of muscles to relax after contracting. This condition usually affects people between the ages of 20 and 30 and can affect a variety of regions of the body, including the facial muscles, the central nervous system, the adrenal glands, the heart, the thyroid gland, the eyes, and the gastrointestinal tract.

Congenital muscular dystrophy

Symptoms of congenital muscular dystrophy become apparent before a child reaches the age of 2. This form of muscular dystrophy is divided into two main subtypes: Ullrich muscular dystrophy and merosin-negative congenital muscular dystrophy.

Facioscapulohumeral muscular dystrophy

On the other hand, another type of muscular dystrophy known as facioscapulohumeral muscular dystrophy, or Landouzy-Dejerine disease, has a distinct impact on the muscles of the face, arms, and shoulders. This special form of muscular dystrophy can lead to difficulty swallowing, a sloped appearance of the shoulders, and an asymmetric appearance of the mouth.

Oculopharyngeal muscular dystrophy

Oculopharyngeal muscular dystrophy is a condition that affects both sexes equally. This disease causes the muscles of the face, neck, and shoulders to weaken over time. Symptoms of this condition include vision problems and difficulty swallowing, drooping eyelids, impaired voice, compromised mobility, and heart problems.

Distal muscular dystrophy

Distal muscular dystrophy, also known as distal myopathy, is a medical condition that predominantly affects the muscles present in the hands and feet. In addition, this condition can also have an impact on the muscles responsible for breathing and pumping blood through the heart. Symptoms associated with distal muscular dystrophy usually develop slowly over time and consist of a deterioration of fine motor movements to lesser degrees of precision.

Emery-Dreifuss muscular dystrophy

Emery-Dreifuss muscular dystrophy usually presents during childhood and has a higher incidence rate in males. The condition manifests through muscle weakness in both the arms and the calves, as well as breathing difficulties, heart problems, and shortening of muscles in areas such as the neck, spine, and joints such as the ankle, knee, and elbow.

Causes of muscular dystrophy

Muscular dystrophy is mainly caused by mutations of the X chromosome. Although each type of the disease has a distinct set of mutations, they all share a common characteristic that affects the body's ability to produce dystrophin.

The gene responsible for producing dystrophin is the largest gene found in the human body. Duchenne and Becker muscular dystrophies have been linked to over a thousand genetic mutations of this gene.

Inheriting a defective gene from a parent is a possibility, even if they show no signs of the corresponding disease. Over time, the individual's ability to perform tasks is gradually affected as the disease progresses. Muscular dystrophy is rarely acquired without any external influence, which makes it difficult to determine an exact cause.

The classification of the most common forms of muscular dystrophies is based on their mode of genetic transmission, which can be segmented into the following categories:

• X-linked recessive transmission: Duchenne, Becker muscular dystrophy;
• autosomal recessive transmission: limb-girdle muscular dystrophies type 2A-2J, congenital dystrophies;
• autosomal dominant transmission: limb-girdle muscular dystrophies type 1A-1E, oculopharyngeal dystrophy, myotonic dystrophies.

Symptoms and manifestations

All forms of muscular dystrophy have a common set of symptoms, involving a gradual weakening of muscle tone, without associated pain. Over time, these symptoms can lead to a reduction in the patient's ability to perform basic motor functions and to move with ease.

Symptoms of this disease usually appear in early childhood. Children affected by it often encounter difficulties mastering fundamental motor skills, such as walking, climbing stairs, and rising from a sitting or lying position. As the disease progresses, the symptoms become increasingly evident, and the progression becomes faster.

As for early symptoms, they are represented by:

• slowed gait;
• muscle pain and stiffness;
• difficulty running or jumping;
• walking on tiptoe;
• difficulty sitting or standing;
• learning difficulties, such as developing speech later than usual;
• frequent falls.

As time passes, symptoms progress quite rapidly, and the patient may face:

• inability to walk;
• shortening of muscles and tendons, which limits movement;
• breathing problems that can become so severe that assisted breathing is necessary;
• curvature of the spine may occur if the muscles are not strong enough to support its structure;
• the heart muscles may be weakened, causing cardiac problems;
• difficulty swallowing, with risk of aspiration and pneumonia.

Diagnosis and investigations

Establishing a diagnosis of muscular dystrophy can be achieved through a variety of methods. The age of diagnosis depends on the initial onset of symptoms. In order to diagnose muscular dystrophy, a series of examinations must be performed, which include:

• Enzyme tests: when the muscles are affected, a substance known as creatine kinase (CK) is produced; if CK levels are elevated in the absence of other forms of muscle injury, it may indicate the presence of muscular dystrophy;
• Genetic testing: given that genetic mutations have been identified in cases of muscular dystrophy, it is a standard procedure to test for these changes;
• Cardiac monitoring: the heart muscles may undergo changes that can be diagnosed using electrocardiography and echocardiography. These two medical procedures are particularly useful in detecting myotonic muscular dystrophy;
• Pulmonary monitoring: checking lung function can provide important information;
• Electromyography: a needle is inserted into the muscles, and the results can reveal signs of muscle disease;
• Biopsy: a sample of muscle tissue is extracted and subjected to microscopic examination, which can reveal signs of the presence of muscular dystrophy.

Treatment and management

Muscular dystrophy is a condition for which there is not yet a complete cure. However, it is possible to considerably improve the quality of life and life expectancy of affected individuals through the use of treatment methods that are tailored to their unique needs.

The specialist physician is the one who prescribes medication treatment, suggests physical rehabilitation, or opts for a combination of both, taking into account the patient's specific needs.

Medication treatment

Two of the most commonly prescribed medications for muscular dystrophy are:

• corticosteroids: this type of medication helps increase muscle strength and slows the progression of the disease, however long-term use can weaken the bones and promote weight gain;
• heart medications: if the disease affects the heart, beta-blockers and angiotensin-converting enzyme inhibitors can be helpful.

Physical therapy and rehabilitation

Maintaining muscle function, preventing contractures, and determining whether orthoses or medical aids are needed are reasons for a medical recovery program. If a patient experiences difficulties with speech or swallowing, speech therapy may also be recommended.

General exercises

To counteract the tendency of the limbs to contract due to the shortening of muscles and tendons, performing a series of movements and stretches can be beneficial. These activities can help maintain flexibility and mobility over a long period of time. In addition, engaging in low-impact aerobic exercises, such as walking or swimming, can also slow the progression of the disease.

Breathing assistance

In cases where the muscles responsible for inhalation and exhalation experience a decrease in strength, it may become necessary to use certain instruments that can increase a person's oxygen intake during sleep. In more severe situations, a person may need a ventilator to help with their breathing functions.

Assistive devices and symptom management

Using wheelchairs and crutch-assisted walking helps maintain the individual's mobility capacity. Braces are also effective in preventing muscles and tendons from contracting too quickly, as well as in providing additional support during movement.

Perspectives in advanced and genetic therapies

New discoveries in this field have led to the identification of a drug called eteplirsen (marketed as Exondys 51), which has been studied by the FDA, the governing body of the food and drug administration in the United States, for the management of specific variants of Duchenne muscular dystrophy.

The US FDA granted accelerated approval to a drug known as viltolarsen (Viltepso). This medication is intended to treat patients with a specific genetic trait who suffer from Duchenne muscular dystrophy. Viltolarsen has the potential to treat the most common form of muscular dystrophy, which usually affects children.

Long-term impact and quality of life

The prognostic outlook depends on the classification of muscular dystrophy, as well as the severity of the associated symptoms. In the case of Duchenne muscular dystrophy, potentially life-threatening complications can occur, such as respiratory and cardiac complications.

Survival rates for people affected by this disease were once limited to only two decades. However, advances in medical research have significantly improved the prognosis. Currently, people with Duchenne muscular dystrophy can expect to live to around 27 years of age, with the possibility of increasing their life expectancy as treatment options continue to evolve.

A person with muscular dystrophy is likely to need specialized help throughout their life.

Prevention and screening

Since the condition is genetic in nature, it is not possible to prevent it in the traditional sense of the word. However, it is always advisable to maintain a healthy lifestyle by abstaining from harmful substances, engaging in regular physical activity, avoiding obesity, and adhering to a well-balanced diet.

It is also very important that, when cases of muscular dystrophy are known in the family, genetic testing be performed to identify the risk of the condition occurring.

Conclusion

Muscular dystrophy is a serious condition that poses a threat to numerous vital functions of the body. However, the implementation of medication treatments and rehabilitation methodologies, together with recent developments in gene therapy (replacing defective genes with healthy ones), can alleviate symptoms and extend the life expectancy of people who have been diagnosed with this disease.

In this regard, it is extremely important for patients to inform themselves periodically about this condition and about effective therapeutic methods, with the aim of implementing appropriate management for the type of muscular dystrophy present.

References

1. Centers for Disease Control and Prevention. What is Muscular Dystrophy?

2. National Institute of Neurological Disorders and Stroke, Muscular Dystrophy.

3. Zhang Y, Mann JR, James KA, McDermott S, Conway KM, Paramsothy P, Smith T, Cai B; MD STARnet. Duchenne and Becker Muscular Dystrophies' Prevalence in MD STARnet Surveillance Sites: An Examination of Racial and Ethnic Differences. Neuroepidemiology. 2021;55(1):47-55. doi: 10.1159/000512647. Epub 2021 Jan 21. PMID: 33477152; PMCID: PMC8045764.

4.Hilbert JE, Ashizawa T, Day JW, Luebbe EA, Martens WB, McDermott MP, Tawil R, Thornton CA, Moxley RT 3rd. Diagnostic odyssey of patients with myotonic dystrophy. J Neurol. 2013 Oct;260(10):2497-504. doi: 10.1007/s00415-013-6993-0. Epub 2013 Jun 27. PMID: 23807151; PMCID: PMC4162528.