Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.

Eyes front and ears open. Class is now in session.

The disease that we will be learning about today is:

Duchenne Muscular Dystrophy

What is Duchenne Muscular Dystrophy?

• Duchenne Muscular Dystrophy’s symptoms begin around ages 3-5
• Most boys who have it do not survive beyond their mid-twenties, and those that do will be wheelchair bound by age 12​​
• More than 300,000 boys live with Duchenne Muscular Dystrophy worldwide​
• New gene-based therapies have recently emerged with noted advances in using conventional gene replacement strategies, RNA-based technology, and pharmacological approaches. In particular, antisense-mediated exon skipping has shown encouraging results and holds promise for the treatment of dystrophic muscle​
• The existing standard of care has been steroids and heart medicine, such as ACE inhibitors, along with good nutrition and physical therapy. These measures can help improve the quality of life and comfort for those with Duchenne, keeping them ambulatory for a little bit longer while work proceeds on therapies to slow or cure the disease.  ​
• The gene was discovered in 1986.  ​
• Although it can — on rare occasions — appear in girls, Duchenne largely occurs in boys. ​
• It affects approximately one out of every 3,500 boys.
• It affects 20,000 in the U.S.
• DMD is the most common form of Muscular Dystrophy (MD), but it is only one of nine total kinds of MD.  ​
• Boys with Duchenne usually inherit it from their mothers through a dystrophin mutation on the X chromosome. A son born to a mother with this mutation has a 50% chance of inheriting the gene and having DMD. A daughter has a 50% chance of inheriting the mutation and becoming a carrier.​

How Do You Get It?

• DMD is a genetic disease. It is caused by a mutation on the X chromosome.  The gene is related to a muscular protein called dystrophin.  This protein keeps muscle cells intact. Its absence causes rapid muscular deterioration as a child with DMD grows. ​
• Each son born to a mother with a dystrophin mutation on one of her two X chromosomes has a 50 percent chance of inheriting the flawed gene and having DMD. Each of her daughters has a 50 percent chance of inheriting the mutation and being a carrier. ​
• Although DMD often runs in a family, it’s possible for a family with no history of DMD to suddenly have a son with the disease.
• Muscles are made up of bundles of fibers (cells). A group of interdependent proteins along the membrane surrounding each fiber helps to keep muscle cells working properly. When one of these proteins, dystrophin, is absent, the result is Duchenne muscular dystrophy.  ​
• Risk factors include:
  • Sex​
    • More common in men​
    • However, girls and women who are DMD carriers may themselves show symptoms of DMD, such as muscle weakness and heart problems ​
  • Genetic Factors​
    • If the mother is a carrier, she has a 50% chance of passing it to her son or giving it to a daughter and making her a carrier.

What Are The Symptoms?

• Physical symptoms of Duchenne muscular dystrophy include:
  • Cardiomyopathy​
    • Lack of dystrophin can weaken the muscle layer in the heart (myocardium).​
    • Over time, sometimes as early as the teen years, the damage done by DMD to the heart can become life-threatening​
  • Lung Disease​
    • Beginning at about 10 years of age, the diaphragm and other muscles that operate the lungs may weaken, making the lungs less effective at moving air in and out. ​
    • Poor respiratory function can lead to headaches, mental dullness, difficulty concentrating or staying awake, and nightmares.  ​
    • Weakened respiratory muscles make it difficult to cough, leading to increased risk of serious respiratory infection. A simple cold can quickly progress to pneumonia.​
  • Learning Difficulties​
    • About a third of boys with DMD have some degree of learning disability. Doctors believe that dystrophin abnormalities in the brain may have subtle effects on cognition and behavior. Learning problems include attention focusing, verbal learning and memory, and emotional interaction.​
• Emotional/Mental symptoms include:
  • Social Isolation​
    • Decreased mobility and independence​
    • The feeling of being different​
    • Having to cope with learning disabilities​
  • Depression/Anxiety ​
    • Presence of their mortality ​
    • Loss of independence​
    • Social stigma​
• Indicators of progression
  • Infants ​
    • Slow to start walking​
  • Toddlers​
    • May have large calf muscles​
  • Preschoolers​
    • May be clumsy and fall often and may have trouble climbing stairs or getting off the floor​
  • School Age​
    • May walk on their toes or the balls of their feet with a slightly waddling gait​
    • May fall frequently​
    • To try to keep their balance, they may stick out their bellies and pull back their shoulders​
    • May have difficulty raising their arms​
  • Children with DMD begin using a wheelchair sometime between ages 7 and 12​
    • Transition to a wheelchair usually is a gradual process; at first, the chair may be required only to conserve the child’s energy when covering long distances. ​
  • Teen years​
    • Activities involving the arms, legs, or trunk may require assistance or mechanical support.​

How Is It Treated?

• DMD is a fatal condition​
• As symptoms begin to appear between ages 2 and 6, the child will usually need regular monitoring by a medical team​
• Most individuals with DMD pass away during their 20s. However, with diligent care, some people with DMD survive into their 30s​
• In the later stages of the disease, most people with DMD will need full-time care to maintain quality of life​
• Thanks to advances in cardiac and respiratory care, life expectancy is increasing and many young adults with DMD attend college, have careers, get married, and have children. Survival into the early 30s is becoming more common, and there are cases of men living into their 40s and 50s​
• The goal of treatment is to increase life span by treating the symptoms​
• There is no cure for Duchenne Muscular Dystrophy​
• Proper mobility equipment like braces and wheelchairs are key for increasing quality of life​
• Cardiac Care​
  • American Academy of Pediatrics recommends that people with DMD have a complete cardiac evaluation by a specialist beginning in early childhood and again at least every other year until age 10.​
• Contractures​
  • As muscle deteriorates, a person with muscular dystrophy often develops fixations of the joints, known as contractures. ​
  • To minimize and postpone contractures, range-of-motion exercises, performed on a regular schedule, may help keep tendons from shortening prematurely.​
  • When contractures have advanced, surgery may be performed to relieve them.​
• Diet​
  • A combination of immobility and weak abdominal muscles can lead to severe constipation, so the diet should be high in fluid and fiber, with fresh fruits and vegetables dominant.​
  • For those who take prednisone, weight gain is common and diet should be altered accordingly.​
• Exercise​
  • Exercise can help build skeletal muscle, keep the cardiovascular system healthy, and contribute to feeling better. But in muscular dystrophy, too much exercise could damage muscle.​
• Treating Cardiac Symptoms​
  • Angiotensin converting enzyme (ACE) inhibitors and beta blockers can slow the course of cardiac muscle deterioration in DMD if the medications are started as soon as abnormalities on an echocardiogram (ultrasound imaging of the heart) appear but before symptoms occur​
• Exon-Skipping therapies​
  • They encourage cells to “skip” or ignore damaged exons – sections of a gene that carry instructions for the rest of the body
  • Eteplirsen is an antisense therapy approved in the US that is effective in around 14 percent of cases.
  • Ataluren is approved for treating DMD in the EU.
  • ​The antisense oligonucleotide golodirsen was approved by the FDA in 2019.
  • Other examples include viltolarsen (FDA approved in August 2020) and casimersen (FDA approved in February 2021)
• Corticosteroids​
  • Found to be effective in slowing the course of DMD. ​
  • Several high-quality studies of these medications in DMD showed a significant increase in strength, timed muscle function (such as the time it took to climb stairs), and pulmonary function.​
• Treating Respiratory Symptoms​
  • A cough assist device or by manual assisted coughing with the help of a caregiver. ​
  • The first step in using assisted ventilation the person receives air under pressure through a mask, nosepiece, or mouthpiece. Noninvasive ventilation usually is required only part-time, often only during sleep.​
  • Some young men choose to switch to an invasive system, which means that a surgical opening called a tracheostomy is performed, allowing air to be delivered directly into the trachea (windpipe).​

Where Can I Learn More???

• Check out our cornerstone on this disease here.
• Learn more about this disease from the Cure Duchenne.