Duchenne Muscular Dystrophy

 Duchenne Muscular Dystrophy 

Overview

Duchenne muscular dystrophy (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.

Symptoms

Symptoms of Duchenne muscular dystrophy (DMD) most often appear between the ages of 2 and 4 years, though they can begin as early as infancy or be noticed later in childhood.

DMD causes muscle weakness that worsens over time, so common symptoms include:

Progressive muscle weakness and atrophy (loss of muscle bulk) that begins in your child’s legs and pelvis. It occurs less severely in their arms, neck and other areas of their body.

Calf muscle hypertrophy (increase in muscle size).

Difficulty climbing up stairs.

Difficulty walking that gets worse over time.

Frequent falls.

Waddling gait (walk).

Toe walking.

Fatigue.

Other common symptoms of DMD include:

Cardiomyopathy.

Breathing difficulties and shortness of breath.

Cognitive impairment and learning differences.

Delayed speech and language development.

Developmental delay.

Scoliosis (spine curvature).

Short stature (height).

About 2.5% to 20% of children AFAB who are carriers of DMD may have symptoms that are usually milder.

CAUSES

DMD is caused by variants of the DMD gene located on the X chromosome. The DMD gene regulates (encodes for) the production of dystrophin, a protein that appears to play an essential role in maintaining the integrity of cell membrane in skeletal (voluntary) and cardiac muscle cells. Dystrophin is found attached to the inner side of the membrane that surrounds muscle fibers. Variants of the DMD gene will result in absence of the dystrophin protein, leading to degeneration of muscle fibers. The body can replace (regenerate) some muscle fibers, but over time more and more muscle fiber is lost. Such degeneration leads to the symptoms and findings associated with DMD. In Becker muscular dystrophy, a related disorder, dystrophin is present, but it is smaller than normal or only present in insufficient levels to function properly.

DMD is inherited in an X-linked pattern. X-linked genetic disorders are conditions caused by a mutated gene on the X chromosome and mostly affect males. Females who have a mutated gene on one of their X chromosomes are carriers for that disorder. Carrier females usually do not have symptoms because females have two X chromosomes and only one carries the mutated gene. Males have one X chromosome that is inherited from their mother and if a male inherits an X chromosome that contains a mutated gene, he will develop the disease.

Female carriers of an X-linked disorder have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have a son affected with the disease and a 25% chance to have an unaffected son.

If a male with an X-linked disorder can reproduce, he will pass the mutated gene to all his daughters who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome instead of their X chromosome to male children.

Some females who inherit a single copy of the a DMD gene variant may have some symptoms associated with DMD such as weakness of certain muscles, especially those of the arms, legs and back. Carrier females who develop symptoms of DMD are also at risk for developing heart abnormalities, which may result in exercise intolerance or shortness of breath. If left untreated, heart abnormalities can cause life-threatening complications in affected females.

Although most boys with DMD inherit the DMD gene variant from their mothers, some may develop the disease as the result of a spontaneous mutation of the DMD gene that occurs randomly for unknown reasons (de novo or sporadic cases).

Diagnosis

Your doctor is likely to start with a medical history and physical examination.

After that, your doctor might recommend:

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 creatine kinase (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.

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). These tests are used to check heart function, especially in people diagnosed with myotonic muscular dystrophy.

Lung-monitoring tests. These tests are used to check lung function.

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.

Treatment

Although there's no cure for any form of muscular dystrophy, treatment for some forms of the disease can help extend the time a person with the disease can remain mobile and help with heart and lung muscle strength. Trials of new therapies are ongoing.

People with muscular dystrophy should be monitored throughout their lives. Their care team should include a neurologist with expertise in neuromuscular diseases, a physical medicine and rehabilitation specialist, and physical and occupational therapists.

Some people might also need a lung specialist (pulmonologist), a heart specialist (cardiologist, a sleep specialist, a specialist in the endocrine system (endocrinologist), an orthopedic surgeon and other specialists.

Treatment options include medications, physical and occupational therapy, and surgical and other procedures. Ongoing assessments of walking, swallowing, breathing and hand function enable the treatment team to adjust treatments as the disease progresses.

Medications

Your doctor might recommend:

Corticosteroids, such as prednisone and deflazacort (Emflaza), which can help muscle strength and delay the progression of certain types of muscular dystrophy. But prolonged use of these types of drugs can cause weight gain and weakened bones, increasing fracture risk.

Newer drugs include eteplirsen (Exondys 51), the first medication to be approved by the Food and Drug Administration (FDA) specifically to treat some people with Duchenne muscular dystrophy. It was conditionally approved in 2016.

In 2019, the Food and Drug Administration (FDA) approved golodirsen (Vyondys 53) for treatment of some people with Duchenne dystrophy who have a certain genetic mutation.

Heart medications, such as angiotensin-converting enzyme (ACE) inhibitors or beta blockers, if muscular dystrophy damages the heart.

Therapy

Several types of therapy and assistive devices can improve the quality and sometimes the length of life in people who have muscular dystrophy. Examples include:

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. Low-impact aerobic exercise, such as walking and swimming, can help maintain strength, mobility and general health. Some types of strengthening exercises also might be helpful. But it's important to talk to your doctor first because some types of exercise might be harmful.

Braces. Braces can help keep muscles and tendons stretched and flexible, slowing the progression of contractures. Braces can also aid mobility and function by providing support for weakened muscles.

Mobility aids. Canes, walkers and wheelchairs can help maintain mobility and independence.

Breathing assistance. As respiratory muscles weaken, a sleep apnea device might help improve oxygen delivery during the night. Some people with severe muscular dystrophy need to use a machine that forces air in and out of their lungs (ventilator).

Surgery

Surgery might be needed to correct contractures or a spinal curvature that could eventually make breathing more difficult. Heart function may be improved with a pacemaker or other cardiac device.

Preventing respiratory infections

Respiratory infections can become a problem in muscular dystrophy. So, it's important to be vaccinated for pneumonia and to keep up to date with influenza shots. Try to avoid contact with children or adults who have an obvious infection.

Type Of Doctor Department : Neurologist