Özge’s background is in research; she holds a MSc. in Molecular Genetics from the University of Leicester and a PhD. in Developmental Biology from the University of London. Özge worked as a bench scientist for six years in the field of neuroscience before embarking on a career in science communication. She worked as the research communication officer at MDUK, a UK-based charity that supports people living with muscle-wasting conditions, and then a research columnist and the managing editor of resource pages at BioNews Services before joining Rare Disease Advisor.
Duchenne muscular dystrophy (DMD) is a severe type of muscular dystrophy characterized by progressive muscle weakness and wasting caused by mutations in the DMD gene.1
Duchenne Muscular Dystrophy Cause
DMD is caused by mutations in the DMD gene, which codes for the dystrophin protein.2 Dystrophin is a long protein that connects the center of the muscle cell with the edge of the cell acting as a spring during muscle contraction.3
In DMD, mutations lead to cells not being able to synthesize any functional dystrophin protein. As a result, muscle cells get damaged at each contraction. With time, this causes muscle atrophy and progressive muscle weakness. Fibrous tissue begins to form and inflammation increases.3
Duchenne Muscular Dystrophy Inheritance
The DMD gene is located on the X chromosome, so the disease mostly affects boys since they do not have a second copy of the X-chromosome to compensate for the one carrying a mutated DMD gene.4
A female carrier of DMD has a 50% chance of passing the disease onto her children. If she has a son and has passed the mutated gene, he will develop DMD; if she has a daughter and passed the faulty gene, her daughter will also be a carrier like her. A female carrier also has a 50% chance of not passing the disease onto her daughters or sons.
A male with DMD will not pass the disease onto any of his sons but he will pass the faulty gene to all his daughters who will all be carriers. Girls can also have some symptoms of DMD such as muscle cramps, weakness, and heart problems but these are usually much milder than in boys.5
Duchenne Muscular Dystrophy Symptoms
The main symptoms of DMD are progressive muscle weakness and wasting (decreased strength and ability to move). These mostly affect boys and usually begin in early childhood.
Affected children usually experience frequent falls, have difficulty rising from a lying or sitting position, and trouble running and jumping. They have a typical waddling gait and tend to walk on their toes. They usually also have large calf muscles and may experience muscle pain and stiffness. Some patients may have learning disabilities and delayed growth.6 The proximal muscles are affected before the distal ones and the lower extremities before the upper ones.7
As the disease progresses, muscles of the heart and diaphragm also become involved. Research has shown that all DMD patients above age 18 present with cardiomyopathy. Muscle weakness in the diaphragm and other muscles involved in breathing eventually impairs respiratory function and increases the risk of serious lung infections.7
Read more about DMD Symptoms.
Duchenne Muscular Dystrophy Diagnosis
Diagnosis begins with a physical examination and a family history of the patient.8 Based on the presence of pseudohypertrophy, lumbar spine deviation, Gower’s sign (weakness of the pelvic girdle or proximal muscles of lower extremities), gait abnormalities, and reduced muscle reflexes, serum creatine kinase (CK) levels should be checked. Although not specific to DMD, CK levels are 10 to 20 times higher than the normal limit by age 2 in patients with muscular dystrophy. They then progressively fall at a rate of 25% per year, eventually returning to normal levels when a considerable amount of muscle tissue has been replaced by fat and fibrotic tissue.8
A muscle biopsy can be performed to distinguish between different forms of muscular dystrophy and other inflammatory diseases. A muscle biopsy can reveal the presence of myopathy and the absence of dystrophin protein following immunostaining. Western blot analysis of the tissue derived from a muscle biopsy can also be performed to predict the severity of the disease and differentiate it from the milder Becker muscular dystrophy. In DMD, the quantity of dystrophin is less than 5% of the normal level.8
A final diagnosis of DMD can be reached via genetic testing analyzing the DMD gene. Genetic diagnosis is indicated for patients with high levels of serum CK and clinical findings of dystrophinopathy. Most cases of DMD are caused by large deletions or duplications in the DMD gene and genetic tests first focus on these types of mutations. If these types of mutations are not present, smaller deletion, duplication, or point mutations are searched.8
Read more about DMD Diagnosis.
Duchenne Muscular Dystrophy Treatment
There is currently no cure for DMD, however, there are treatments available to ease the symptoms and increase patients’ quality of life. The mainstay medical treatment is corticosteroid treatment. Physical therapy can improve muscle strength and function. Respiratory therapy can aid with breathing problems. Occupational therapy can help with swallowing problems as can diet and nutrition counseling. Finally, behavioral therapy can improve cognitive function.9
There are also a number of disease-modifying treatments that have been approved for DMD, which may delay the progression of the disease. These include Translarna™ (ataluren), which is authorized for use in the EU but not yet approved in the US, and the exon-skipping drugs such as Exondys 51 (eteplirsen), Vyondys 53 (golodirsen), and Amondys 45 (casimersen) already approved by the US Food and Drug Administration (FDA), which could help patients with certain types of mutations in the DMD gene.10,11
Read more about DMD Treatment.
- Duchenne Muscular Dystrophy (DMD). Muscular Dystrophy Association. Accessed July 8, 2021.
- DMD gene. MedlinePlus. Updated August 18, 2020. Accessed July 8, 2021.
- Causes/inheritance. Muscular Dystrophy Association. Accessed July 8, 2021.
- About Duchenne Muscular Dystrophy. National Human Genome Research Institute. Updated April 18, 2013. Accessed July 8, 2021.
- Duchenne Muscular Dystrophy. Kids Health. Accessed July 8, 2021.
- Muscular dystrophy. Mayo Clinic. January 30, 2020. Accessed July 8, 2021.
- Signs and symptoms. Muscular Dystrophy Association. Accessed July 8, 2021.
- Diagnosis. Muscular Dystrophy Association. Accessed July 8, 2021.
- Duchenne Muscular Dystrophy: our approach to care. Stanford Health Care. Accessed July 8, 2021.
- Translarna. European Medicines Agency. Accessed July 8, 2021.
- Building an industry-leading genetic medicine pipeline. Sarepta Therapeutics. Accessed July 8, 2021.
Article reviewed by Harshi Dhingra, MD, on July 1, 2021.