Medication
Until recently, children with Duchenne muscular dystrophy (DMD) did not often live beyond their teens. However, improvements in cardiac and respiratory care mean that life expectancy is increasing, with many DMD patients reaching their 30s, and some living into their 40s and 50s.
Procedures
What are some of the best treatment methods for muscular dystrophy?
- Medicines Let’s start first with some of the medicines that the doctor may prescribe: Corticosteroids: The first one would be corticosteroids, which are often prescribed to patients that have ...
- Therapy Stretching Exercises: The first type of physical therapy that can be done would be range of motion and stretching exercises. ...
- Surgery
Therapy
What are the treatments for muscular dystrophy (MD)?
- Physical Therapy. Beginning physical therapy early can help keep muscles flexible and strong. ...
- Respiratory Therapy. Because the body relies on muscles such as the diaphragm to breathe, weakened muscles from MD may affect breathing.
- Speech Therapy. ...
- Occupational Therapy. ...
- Surgery. ...
- Drug Therapy. ...
- Gene-Based Therapy. ...
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- Upward slanting eyes
- Small, low set ears
- Small nose with a flat nasal bridge
- Flattened face
- Short neck
- A tongue that sticks out
- Small hands and feet
- Single palmar crease (line across the palm)
- Curved and small pinky fingers
- Hypotonia (low muscle tone)
What is the life expectancy of muscular dystrophy?
What is the best medicine for muscular dystrophy?
What are treatments used to treat muscular dystrophy?
What is the life expectancy of someone with dystrophy?
What is the defect of Duchenne muscular dystrophy?
Duchenne muscular dystrophy is caused by a defective gene for dystrophin (a protein in the muscles). However, it often occurs in people without a known family history of the condition. The condition most often affects boys due to the way the disease is inherited.
Where is the mutation found in Duchenne muscular dystrophy?
DMD is inherited in an X-linked pattern because the gene that can carry a DMD-causing mutation is on the X chromosome. Every boy inherits an X chromosome from his mother and a Y chromosome from his father, which is what makes him male. Girls get two X chromosomes, one from each parent.
Where is muscular dystrophy located?
DMD, the largest known human gene, provides instructions for making a protein called dystrophin. This protein is located primarily in muscles used for movement (skeletal muscles) and in heart (cardiac) muscle. Small amounts of dystrophin are present in nerve cells in the brain.
Which protein is defective in cases of muscular dystrophy?
Mutations that affect the muscle BM cause congenital muscular dystrophy; those that affect the cytoskeletal protein dystrophin cause Duchenne and Becker muscular dystrophy; and those that affect transmembrane proteins called sarcoglycans cause limb-girdle muscular dystrophy (3).
What gene mutation causes muscular dystrophy?
Causes. Mutations in the DMD gene cause the Duchenne and Becker forms of muscular dystrophy. The DMD gene provides instructions for making a protein called dystrophin . This protein is located primarily in skeletal and cardiac muscle, where it helps stabilize and protect muscle fibers.
What type of gene mutation causes DMD?
Duchenne muscular dystrophy is caused by a change in the dystrophin gene. Genes are small pieces of DNA that contain the instructions for how to make a protein. The dystrophin gene is basically a recipe for how to make the dystrophin protein.
What part of the body does muscular dystrophy affect?
Muscles around the eyes and mouth are often affected first, followed by weakness around the shoulders, chest, and upper arms. A particular pattern of muscle wasting causes the shoulders to appear to be slanted and the shoulder blades to appear winged. Muscles in the lower extremities may also become weakened.
How is Duchenne muscular dystrophy caused?
It is caused by a genetic mutation on one of the mother's X chromosomes, and researchers have identified some of the affected genes. Duchenne muscular dystrophy is caused by a genetic problem in producing dystrophin, a protein that protects muscle fibers from breaking down when exposed to enzymes.
What causes muscular dystrophy?
In most cases, muscular dystrophy (MD) runs in families. It usually develops after inheriting a faulty gene from one or both parents. MD is caused by mutations (alterations) in the genes responsible for healthy muscle structure and function.
What is the function of dystrophin?
Dystrophin is a subsarcolemmal rod-shaped protein that stabilizes the sarcolemma by attaching the actin cytoskeleton to the extracellular matrix through the dystrophin-associated glycoprotein complex. This connection protects muscle cells from contraction-induced damage.
Is Duchenne muscular dystrophy a deletion mutation?
Duchenne muscular dystrophy is an inherited muscle wasting disease with severe symptoms and onset in early childhood. Duchenne muscular dystrophy is caused by loss-of-function mutations, most commonly deletions, within the DMD gene.
How early can you walk with Duchenne muscular dystrophy?
The mean age for walking in boys with Duchenne muscular dystrophy is 18 months. There is progressive muscle weakness of the legs and pelvic muscles, which is associated with a loss of muscle mass (wasting). This muscle weakness causes a waddling gait and difficulty climbing stairs. Muscle weakness also occurs in the arms, neck, and other areas, but not as severely or as early as in the lower half of the body.
When do Duchenne muscular dystrophy symptoms appear?
The symptoms usually appear before age 6 and may appear as early as infancy. Typically, the first noticeable symptom is delay of motor milestones, including sitting and standing independently. The mean age for walking in boys with Duchenne muscular dystrophy is 18 months.
How to detect dystrophin in muscle?
A muscle biopsy (taking a sample of muscle) for dystrophin studies can be done to look for abnormal levels of dystrophin in the muscle. The dystrophin protein can be visualized by staining the muscle sample with a special dye that allows you to see the dystrophin protein. A muscle which has average amounts of dystrophin will appear with the staining technique as though there is caulking around the individual muscles cells and it is holding them together like window panes. A boy with Duchenne, on the other hand, will have an absence of dystrophin and appear to have an absence of the caulking around the muscle cells. Some individuals can be found to have an intermediate amount of the dystrophin protein. Often these boys are classified as having Becker muscular dystrophy.
What is the name of the mutation that causes muscular dystrophy?
About Duchenne Muscular Dystrophy. Duchenne muscular dystrophy (DMD) is a rapidly progressive form of muscular dystrophy caused by a mutation in the DMD gene.
What is the cause of DMD?
It is caused by an alteration (mutation) in a gene, called the DMD gene that can be inherited in families in an X-linked recessive fashion, but it often occurs in people from families without a known family history of the condition.
Do boys with Duchenne muscular dystrophy have dystrophin?
Boys with Duchenne muscular dystrophy do not make the dystrophin protein in their muscles. Duchenne muscular dystrophy affects approximately 1 in 3500 male births worldwide. Because this is an inherited disorder, risks include a family history of Duchenne muscular dystrophy.
Does prednisone help with DMD?
The medication prednisone - a steroid - is given to improve the strength and function of individuals with DMD. Prednisone has been shown to prolong the ability to walk by 2 to 5 years. However, the possible side effects of prednisone include weight gain, high blood pressure, behavior changes, and delayed growth.
What is Duchenne muscular dystrophy?
Duchenne muscular dystrophy ( DMD) affects the muscles, leading to muscle wasting that gets worse over time. DMD occurs primarily in males, though in rare cases may affect females. The symptoms of DMD include progressive weakness and loss (atrophy) of both skeletal and heart muscle. Early signs may include delayed ability to sit, stand, ...
How is Duchenne muscular dystrophy diagnosed?
Duchenne muscular dystrophy (DMD) is diagnosed in young boys based on clinical examination, signs and symptoms, family history, and may be confirmed by the results of genetic testing. A muscle biopsy may be done to remove a small piece of muscle for examination under a microscope. Blood tests looking for increased levels of certain special proteins called muscle enzymes are used to check for muscle damage. [1] [7]
What causes muscle weakness in children?
Heart and breathing problems also begin in the teen years and lead to serious, life threatening complications. DMD is caused by genetic changes ( DNA variants) in the DMD gene.
Why do boys with DMD have breathing problems?
By the early teens, most boys with DMD are using a wheelchair. Breathing problems occur due to weakness of the diaphragm and the other muscles around the lungs. Scoliosis and tight joints ( contractures) may develop as muscle loss gets worse.
When was deflazacort approved?
FDA-approved indication: February 2017 , deflazacort (Emflaza) was approved for the treatment of Duchenne Muscular Dystrophy in patients 5 years of age and older. National Library of Medicine Drug Information Portal. Medline Plus Health Information.
What is delayed motor development?
Delayed motor development (taking longer to learn to sit, stand, or walk)
Is DMD inherited?
DMD is inherited in an X-linked recessive pattern and may occur in people who do not have a family history of DMD. Diagnosis of DMD is based on the symptoms, clinical exam, and the result of a biopsy to remove a small piece of muscle for examination under a microscope.
What is the function of dystrophin?
It is in close association with other cytoskeletal proteins, including F-actin via its N-terminus and part of the rod domain; it also binds to dystroglycan via its cysteine-rich domain and to dystrobrevin and syntrophin via the C-terminal domain.19Thus, dystrophin provides structural stability to the skeletal muscle by connecting the sarcolemma and the basal lamina of the extracellular matrix to the inner cytoskeleton. It is also essential for cell survival via its transmembrane signaling function and modulation of vasomotor response to physical activity.20Th ree isoforms of dystrophin are derived from independent promoters in the brain, retina, and Purkinje cerebellar neurons; mutations in these tissue specific isoforms of dystrophin likely contribute to the extramuscular manifestations of DMD, including cognitive, behavioral, and learning difficulties.19
What is the most common form of muscular dystrophy in childhood?
Duchenne muscular dystrophy (DMD) is the most common form of muscular dystrophy in childhood. It is caused by mutations of the DMDgene, leading to progressive muscle weakness, loss of independent ambulation by early teens, and premature death due to cardiorespiratory complications. The diagnosis can usually be made after careful review of the history and examination of affected boys presenting with developmental delay, proximal weakness, and elevated serum creatine kinase, plus confirmation by muscle biopsy or genetic testing. Precise characterization of the DMDmutation is important for genetic counseling and individualized treatment. Current standard of care includes the use of corticosteroids to prolong ambulation and to delay the onset of secondary complications. Early use of cardioprotective agents, noninvasive positive pressure ventilation, and other supportive strategies has improved the life expectancy and health-related quality of life for many young adults with DMD. New emerging treatment includes viral-mediated microdystrophin gene replacement, exon skipping to restore the reading frame, and nonsense suppression therapy to allow translation and production of a modified dystrophin protein. Other potential therapeutic targets involve upregulation of compensatory proteins, reduction of the inflammatory cascade, and enhancement of muscle regeneration. So far, data from DMD clinical trials have shown limited success in delaying disease progression; unforeseen obstacles included immune response against the generated mini-dystrophin, inconsistent evidence of dystrophin production in muscle biopsies, and failure to demonstrate a significant improvement in the primary outcome measure, as defined by the 6-minute walk test in some studies. The long-term safety and efficacy of emerging treatments will depend on the selection of appropriate clinical end points and sensitive biomarkers to detect meaningful changes in disease progression. Correction of the underlying mutations using new gene-editing technologies and corticosteroid analogs with better safety profiles offers renewed hope for many individuals with DMD and their families.
How many exons are in the DMD gene?
The DMDgene is one of the largest known human genes. It contains 79 exons, which include an actin-binding domain at the N-terminus, 24 spectrin-like repeat units, a cysteine-rich dystroglycan binding site, and a C-terminal domain.7,8The extremely large size of the gene contributes to a complex mutational spectrum, with >7,000 different mutations and a high spontaneous mutation rate.9Approximately two-thirds of cases are maternally inherited; the remaining one-third occurs as a result of spontaneous mutations.10Large (one or more exons) deletions account for approximately two-thirds of all DMDmutations; the rest are due to duplications and small deletions, insertions, point mutations, or splicing mutations.11,12The severe phenotype associated with DMD is most often caused by out-of-frame mutations, with complete loss of the dystrophin protein.13,14In-frame mutations that allow for the synthesis of an internally truncated but partially functional protein are associated with a milder and more variable phenotype known as Becker muscular dystrophy or X-linked dilated cardiomyopathy; exceptions to the reading frame hypothesis occur in <10% of all DMDmutations.10,15Disease severity is also affected by other genetic modifiers distinct from the DMDgene, including single nucleotide polymorphism of the latent transforming growth factor-beta(TGF-β) binding protein 4(LBP4) gene and osteopontin, encoded by the secreted phosphoprotein 1(SPP1) gene; both genes appear to influence disease progression in DMD by modifying the age at loss of independent ambulation, the age at onset of dilated cardiomyopathy, and the clinical response to corticosteroid treatment.16–18
What happens when you lose dystrophin?
Loss of dystrophin as a result of DMDgene mutations disrupts the dystrophin glycoprotein complex, leading to increased muscle membrane fragility. A cascade of events including influx of calcium into the sarcoplasm, activation of proteases and proinflammatory cytokines, and mitochondrial dysfunction results in progressive muscle degeneration.20–22In addition, displacement of neuronal nitric oxide synthase contributes to tissue ischemia, increased oxidative stress, and reparative failure.23Disease progression is characterized by increasing muscle necrosis, fibrosis, and fatty tissue replacement and a greater degree of fiber size variation seen in subsequent muscle biopsies.24
How to diagnose DMD?
The diagnosis of DMD can usually be made after a careful review of the clinical history, physical examination, and confirmation by additional investigations, including muscle biopsy and/or molecular genetic testing.3A positive family history of DMD is not required, as approximately one-third of cases may occur as a result of spontaneous mutation. The presence of motor developmental delay with or without speech delay and muscle hypertrophy in a young boy should trigger the order of serum CK as an initial diagnostic screen for DMD, especially if the child also has signs of proximal muscle weakness, manifesting as an abnormal waddling gait, or a positive Gowers’ sign (Figure 1).25As shown in the case illustration earlier, the muscle enzymes as measured by serum CK are usually markedly elevated. Raised muscle enzymes in DMD also contribute to persistently high serum alanine and aspartate transaminase levels; in some cases, the diagnosis may be delayed due to initial investigations for suspected hepatic dysfunction.
Is there a cure for DMD?
There is presently no cure for DMD. Current treatment strategies focus on optimizing growth and development, promoting well-balanced diet, participating in physical and recreational activity, and delaying the onset of secondary complications through ongoing medical and psychosocial support.35Supportive interventions including timely treatment with corticosteroids, early afterload reduction for cardiomyopathy, aggressive management of heart failure, noninvasive positive pressure ventilation, and effective airway clearance strategies have contributed to prolonged survival of individuals with DMD. The mean age of death from DMD increased from 14.4 years in the 1960s to 25.3 years in the 1990s, with corresponding improvement in affected individuals’ health-related quality of life.36–38
What is the best treatment for MD?
Drug Therapy. Certain medications can help delay damage to muscles or minimize the symptoms of MD. These can include the following: Glucocorticoids 4, 5 such as prednisone or deflazacort , which was approved by the U.S. Food and Drug Administration (FDA) for treating DMD in 2017.
How to help MD with facial weakness?
MD patients who experience weakness in the facial and throat muscles may benefit from speech therapy to teach them how to maximize their muscle strength. Some methods include slowing the pace of their speech, pausing more between breaths, 3 and using specialized communication equipment.
What is the first FDA approved screening platform for lysosomal storage disorder?
SEEKER® – The First FDA-Authorized Newborn Screening Platform for Lysosomal Storage Disorders
Does exon skipping cure DMD?
In exon skipping, more muscle protein is available and usable, even though it is shorter than the normal protein. FDA approved eteplirsen for treatment of DMD in 2016, 8 golodirsen in 2019, 9 and viltolarsen in 2020. 10 These treatments require weekly intravenous injection and do not cure DMD.
What is the FDA approved medication for Duchenne Dystrophy?
Heart medications, such as angiotensin-converting enzyme (ACE) inhibitors or beta blockers, if muscular dystrophy damages the heart.
How to keep joints flexible with muscular dystrophy?
Range-of-motion and stretching exercises. Muscular dystrophy can restrict the flexibility and mobility of joints. Limbs often draw inward and become fixed in that position. Range-of-motion exercises can help to keep joints as flexible as possible. Exercise.
Why do people with muscular dystrophy need a ventilator?
Some people with severe muscular dystrophy need to use a machine that forces air in and out of their lungs (ventilator).
What tests can be done to determine if you have muscular dystrophy?
Enzyme tests. Damaged muscles release enzymes, such as creatine kinase (CK), into your blood. In a person who hasn't had a traumatic injury, high blood levels of CK suggest a muscle disease. Genetic testing. Blood samples can be examined for mutations in some of the genes that cause types of muscular dystrophy.
What is muscle biopsy?
Muscle biopsy. A small piece of muscle can be removed through an incision or with a hollow needle. Analysis of the tissue sample can distinguish muscular dystrophies from other muscle diseases. Heart-monitoring tests (electrocardiography and echocardiogram).
What is the test for muscle disease?
Electromyography. An electrode needle is inserted into the muscle to be tested. Electrical activity is measured as you relax and as you gently tighten the muscle. Changes in the pattern of electrical activity can confirm a muscle disease.
When was Exondys 51 approved?
It was conditionally approved in 2016.
