Getting to Know Duchenne Muscular Dystrophy

Duchenne Muscular Dystrophy (DMD) is a condition that causes skeletal and heart muscle weakness that quickly gets worse with time. Symptoms usually begin by the age of 6 years, and the condition mainly affects children assigned male at birth. There’s currently no cure, so treatment involves managing symptoms and improving quality of life.

What is DMD?

DMD is a condition that weakens skeletal and heart muscle that quickly gets worse with time. It’s the most common form of muscular dystrophy.

Most cases of DMD are inherited as an X-linked recessive trait (passed on through the mother, who is a carrier), but approximately 30% of cases are due to new genetic changes (mutations) that happen randomly and aren’t inherited.

Who does DMD affect?

DMD mainly affects children assigned male at birth (AMAB), but children assigned female at birth (AFAB) who are carriers for DMD can sometimes have milder symptoms.
Symptoms of muscle weakness usually appear by the age of 2 years to 4 years, but sometimes, are noted as late as 6 years.

How common is DMD?

DMD affects about 1 in 3,600 male live-born infants. It’s the most common type of severe hereditary myopathies (disorders of skeletal muscles).

Is DMD fatal?

Yes, DMD is ultimately fatal. Most people with the condition die from lung or heart issues caused by it.

Symptoms and Causes

What are the symptoms of DMD?

The DMD children start showing up signs and symptoms before 6 years of age and they include:

• Progressive muscle weakness
• Difficulty walking
• Loss of ability to routine activities
• Frequent falls
• Learning disabilities
• Enlarged calves
• Fatigue
• Weakness in the legs, pelvis, arms and neck which is rapidly worsening
• Failure to develop motor skills

What causes DMD?

Caused by a gene defect (mutation) that affects the gene that helps the body to produce a protein called dystrophin.

• Dystrophin keeps the muscles intact. Absence of the protein causes muscle degeneration.
• The disease follows X – linked recessive pattern of inheritance. This means that males are much more likely to get affected, as they inherit the X – chromosome from mother. All female children will be carriers.

Risk factors include

• Family history – a defective gene is carried and passed on through women
• Gender – affects almost always the boys

Diagnosis and Tests

How is DMD diagnosed?

Blood test: Creatine phosphokinase levels are measured to detect the levels of enzyme creatine phosphokinase. Large quantities indicate muscle damage.
Muscle biopsy: A small sample of muscle tissue is observed under the microscope. Low levels of dystrophin indicates DMD.
Genetic test: To look for gene mutations.
Electromyography (EMG): An electrode is inserted into the muscle to detect changes in the electrical activity.

Management and Treatment

Treatment Approaches for Duchenne Muscular Dystrophy

There’s currently no cure for Duchenne muscular dystrophy (DMD), so the main goal of treatment is to manage symptoms and improve quality of life.

Pharmacological Treatments

• Corticosteroids:
  Prednisone and Deflazacort are commonly prescribed corticosteroids for DMD. They help slow muscle degeneration, improve muscle strength, and delay the progression of scoliosis and cardiomyopathy. Corticosteroids can also improve pulmonary function and prolong the ability to walk.
• Eteplirsen:
  Eteplirsen (Exondys 51) is an exon-skipping drug approved by the FDA for DMD patients with a confirmed mutation of the DMD gene amenable to exon 51 skipping. It aims to increase the production of a functional dystrophin protein, albeit shorter than the normal one.
• Viltolarsen:
  Viltolarsen (Viltepso) is another exon-skipping therapy targeting exon 53 of the DMD gene, helping to produce a functional dystrophin protein. It is designed for patients with specific mutations amenable to exon 53 skipping.
• ACE Inhibitors and Beta-Blockers:
  ACE inhibitors (e.g., Enalapril, Lisinopril) and beta-blockers (e.g., Carvedilol, Metoprolol) are used to manage cardiomyopathy. Early initiation can help maintain heart function and prevent the progression of heart failure.

Gene Therapy

Gene therapy is an emerging field showing promise in the treatment of DMD. It aims to address the root cause by correcting or compensating for the defective gene.

• Micro-dystrophin Gene Therapy:
  Micro-dystrophin: This therapy involves delivering a shortened but functional version of the dystrophin gene to muscle cells using viral vectors. It aims to restore the production of dystrophin and improve muscle function. Clinical trials are ongoing, showing promising early results.
• Exon Skipping:
  Exon skipping techniques: These use synthetic antisense oligonucleotides (AONs) to skip over faulty parts of the gene, allowing for the production of a shorter but functional dystrophin protein. Eteplirsen and Viltolarsen are examples of this approach.
• CRISPR/Cas9:
  CRISPR/Cas9: This genome-editing technology can potentially correct mutations directly in the DNA of muscle cells. Research is ongoing to determine its safety and efficacy for DMD.

Physical Therapy and Exercise

Physical therapy and regular exercise play crucial roles in managing DMD, helping to maintain muscle function and delay the progression of symptoms.

• Stretching and Range-of-Motion Exercises:
  These exercises help prevent contractures (permanent tightening of muscles, tendons, and ligaments) and maintain joint flexibility. Regular stretching is essential, especially for the lower limbs.
• Low-Impact Aerobic Exercise:
  Activities like swimming and cycling are recommended to keep muscles active without causing excessive strain. These exercises help maintain cardiovascular health and muscle function.
• Strengthening Exercises:
  Gentle strengthening exercises can help maintain muscle strength. It’s crucial to avoid high-resistance exercises that could damage muscles.
• Breathing Exercises:
  Respiratory therapy may include exercises to strengthen breathing muscles and techniques to help clear mucus from the lungs. Non-invasive ventilation support might be necessary as the disease progresses.
• Adaptive Equipment:
  The use of braces, orthotic devices, and mobility aids like wheelchairs can help maintain independence and mobility as muscle weakness progresses.

Specialist To Consult

• Pediatrician
  Specializes in the health of children, including physical, behavioral, and mental health issues
• Physical therapist
  A health professional who helps patients reduce pain and improve or restore mobility.
• Medical geneticist
  Specializes in the diagnosis and management of hereditary disorders.
• Occupational Therapist
  A healthcare professional who helps in development, recovery, or management of everyday activities, or occupations.

Prevention

Can DMD be prevented?

As DMD is an inherited condition, there’s nothing you can do to prevent it. About a third of cases happen randomly without a family history of the condition.

If you’re concerned about the risk of passing on DMD or other genetic conditions before trying to have a biological child, talk to your healthcare provider about genetic counseling. In some situations, prenatal testing may be able to diagnose DMD in early pregnancy.

Living With

How do I take care of someone with DMD?

If you’re taking care of someone with DMD , it’s important to advocate for them to ensure they get the best medical care and access to therapy that can help them have the best quality of life.
You and your family may also want to consider joining a support group to meet others who can relate to your experiences.

When should my child see their healthcare provider about DMD?

If your child has been diagnosed with DMD, they’ll need to see their team of healthcare providers regularly to receive treatment and monitor symptoms.

Seeking Help and Support for DMD

Living with DMD can be challenging, but there are many resources and organizations dedicated to providing support, information, and assistance to patients and their families. Here are some ways to seek help:

1. Connect with Support Organizations

Several organizations offer valuable resources and support for those affected by DMD. These organizations can provide information on the latest research, treatment options, and connect you with a community of others facing similar challenges. Some of the key organizations include:

• Muscular Dystrophy Association (MDA): Provides comprehensive support and resources for individuals with muscular dystrophy, including DMD.
• Parent Project Muscular Dystrophy (PPMD): Focuses specifically on DMD, offering support, advocacy, and information about research and clinical trials.
• CureDuchenne: Aims to find a cure for DMD and offers support to families through various programs and initiatives.

2. Utilize Online Resources

Numerous online platforms offer educational materials, forums for connecting with other patients and caregivers, and updates on the latest research and treatments. Some useful websites include:

• DuchenneXchange: An online community and resource hub for those affected by DMD.
• DuchenneConnect: A registry that connects patients with research studies and provides information on DMD.

3. Engage with Local Support Groups

Local support groups can offer a sense of community and practical advice from others who understand the daily challenges of living with DMD. These groups often meet regularly and can provide both emotional support and valuable information.

By leveraging these resources and connecting with the right support networks, patients and families can better navigate the challenges of DMD and stay informed about the latest advancements in treatment and care.

Summary

DMD is a severe muscle-wasting condition that worsens over time, primarily affecting males, though it can occasionally affect females. Symptoms usually appear between ages 2 and 4 and include progressive muscle weakness, difficulty walking, frequent falls, and learning disabilities. DMD is caused by mutations in the DMD gene and follows an X-linked recessive inheritance pattern. Diagnosis involves symptom observation, clinical exams, muscle biopsies, and genetic testing.

While there is no cure for DMD, treatments focus on managing symptoms and improving quality of life. These include corticosteroids, medications for heart function, physical and occupational therapies, and surgeries for severe complications. Support from healthcare professionals and organizations can help families navigate the challenges of DMD, providing hope and resources for better management of the condition.