Duchenne muscular dystrophy, also known as “DMD”, is a genetic disorder characterized by rapid progressive muscle degeneration and wasting in children, which begins by affecting a particular group of muscles, before spreading out throughout the body. It is the most common childhood form yet a very severe type of muscular dystrophy. The disease occurs primarily in males (1 in 3500 to 5000 newborn males), and it is very rare for girls to develop it.
Initial mild symptoms are often noticed in boys from 1-6 years of age. There might be occasional signs of clumsiness, which include trouble walking, difficulty in raising the
front of the foot and frequent falls.
More obvious signs include delayed motor development, where children with DMD normally are slower to sit, stand or walk independently. The average age of walking for DMD boys is about 18 months. Muscle enlargement is common, particularly in the calves, since the muscle cells are replaced by fat and connective tissue. As well as that, children with DMD frequently walk on their toes to keep their balance. The Gower maneuver is another common symptom, when children with neuromuscular disorder often use their hands when attempting to get up from the floor, and will move their hands up their tights in order to stand up fully.
From the ages between 6-10 there is a rapid decline in muscle strength (Refer to Note 1 below). By 10 years old, braces might be required for walking. By age 12 most boys will require a wheelchair full-time.
|(Note 1) : DMD 持續性肌肉萎縮和相關的併發症|
Progressive muscle weakness and wasting (atrophy) first begins in the muscles of the hips, pelvic areas and thighs, leading to difficulty standing, ascending stairs, and maintaining balance. As the diseases progresses, it affects muscles in the shoulders and arms, leading to functional difficulties, such as raising the arms. Eventually, DMD affects all the muscles in the body, including the heart and breathing muscles. During muscle degeneration joints may become more tight and rigid (contractures), affecting the knee, hip, elbow, wrist and finger. Over time, scoliosis, the curvature of the spine may develop as muscles are unable to hold the spine. There will be more walking and movement restrictions and once wheelchair dependent, risk of respiratory and cardiac complications increases. Cardiac problem involves the gradual enlargement of the heart (cardiomyopathy), which weakens the cardiac muscle and prevents it from pumping blood efficiently. In severe cases, abnormal heart rhythm and heart failures may result. Breathing problems includes respiratory failure, as muscles surrounding the lungs such as the diaphragm weaken. Cardiac and/or respiratory failure are still the main causes of death in DMD.
DMD is caused by a mutation of the dystrophin gene, which is on the X chromosome preventing the body from producing dystrophin. Dystrophin is a protein which keeps muscles strong and healthy and without it, muscle cells become fragile and weaken over time.
Carriers are females who have a normal dystrophin gene on one X chromosome and an abnormal dystrophin on the other X chromosome. Most carriers appear normal, but a minority can exhibit symptoms associated to DMD such as skeletal muscle weakness and cramping. As well as that, they have a higher risk of developing cardiac associated problems.
DMD affects primarily on boys because the dystrophin gene is on the X chromosome. Males have only one X chromosome whereas females have two. Therefore, a female carrier will not develop the disease as the normal gene on one X chromosome compensates for the gene defect on the other X chromosome. A DMD mother has a 50% chance passing the genetic mutation on to her children – any son who receives the defective gene will have the disease as male only has one copy of the dystrophin gene while any daughter who receives the defective gene will become a carrier herself, the same way as her mother carrier.
People with the condition usually only live into their 20s, but technological advances and proactive standards of care have allowed some patients to live to their 30s and in some cases, 40s.
Although there is no cure for DMD at the moment, there are certain therapies and medicines to help alleviate symptoms and control related complications, providing an improved quality of life. Treatments are aimed at the specific symptoms present in each individual case. The emphasis of the treatments will vary greatly at different stages in DMD course. Our neuromuscular team will recommend appropriate interventions for your child.
While no cure yet exists for DMD, in the past 2 decades seen considerable R&D effort and progress leading to a number of potential treatment approaches – some address the underlying cause of DMD which is a lack of dystrophin, and others aims to fix the resulting symptoms caused by the lack of dystrophin in the muscle. These include gene therapy, exon skipping, ataluren, creatine, deacetylase inhibitors, myostatin inactivation, and cell therapy (myoblast treatment, and/or the use of stem cells).
In 2016, Exondys 51 (eteplirsen) injection was approved by US Food and Drug Administration (FDA) to treat DMD and is the first drug approved for this condition. Exondys 51 is specifically indicated for patients who have a confirmed mutation of the dystrophin gene amenable to exon 51 skipping, which affects about 13 percent of the population with DMD, representing only a small sub-population of DMD.
In 2017, Emflaza (deflazacort) was approved by FDA to treat patients age 5 years and older with DMD.
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