Becker Muscular Dystrophy — A Multi-Systemic, Progressive Disease with Irreversible Consquences
Becker muscular dystrophy is a chronic, progressive, and multi-system disease, which can result in irreversible loss of muscle function, and may lead to loss of ambulation and premature death.1,3,4
Becker muscular dystrophy is an X-linked recessive disease caused by mutations in the DMD gene, affecting approximately 1:18,000 male births.3
The disease imposes significant physical, emotional, financial, and social impacts on the individual and their caregivers. Individuals with Becker experience contraction-induced muscle damage, which is the primary driver of muscle loss and impaired motor function in muscular dystrophies.4
Individuals living with Becker may have a near normal life expectancy, although some have complications and even mortality as early as their 20’s. While a mean age of death of 47 has been quoted for these individuals, overall life expectancy is longer.4,5
There is currently no approved treatment for Becker. Disease management consists of symptom management and physiotherapy; when utilized early in the course of disease, it can help preserve muscle and overall function. There are approved cardiac medicines to help manage Becker related cardiac complications which can improve patient prognosis.3
In individuals living with Becker, functional decline can begin at any age, but once muscle loss begins, the decline in function is steady, unrelenting, and irreversible.2
Natural History of Becker Muscular Dystrophy
- The North Star Ambulatory Assessment (NSAA) measures an individual’s ability to perform 17 assessments which tests the speed and functionality of their motor skills.
- Several natural history studies demonstrate a North Star Ambulatory Assessment (NSAA) average score decline of 1.2 to 1.8 points annually in individuals with Becker already showing signs of progression.2,6,7 Practically, this means that they will have loss or impairment of 1-2 physical functions annually.
- For example, over a 2-year period, for individuals living with Becker muscular dystrophy this could mean:
- From using a toilet independently to having to ask for help to get up from using a toilet.
- From being able to navigate stairs or step over a sidewalk curb on one’s own, to requiring assistance from another person or from a mobility device.
- From being able to get up from a fall to requiring someone else’s help to get back up.
Clinical presentation, symptom onset, and age of initial functional decline may vary in individuals living with Becker.2 Once the functional decline begins, it is consistent and irreversible, impacting various aspects of their daily lives.
Becker Muscular Dystrophy – Mechanism of Disease
Contraction-induced muscle injury is the key driver of disease progression in Becker muscular dystrophy where fully functional dystrophin is missing.9
Progressive and Irreversible Loss of Function and Mobility are the Defining Characteristics of Becker Muscular Dystrophy1,3,4
Over time muscle weakness progresses in individuals living with Becker, limiting their ability to perform everyday activities such as walking, climbing stairs and picking up things up with their hands. Becker muscular dystrophy also impacts other parts of the body including the cardiac, respiratory, gastrointestinal, and endocrine systems.3
Progressive, Multi-Systemic Symptoms
The frequency of loss of ambulation increases with increasing age.2
Musculoskeletal
Ongoing contraction-induced muscle injuries in Becker leads to irreversible loss of muscle and function4.
- Skeletal muscle weakness, muscle cramps, and pain are a key presenting symptoms in Becker. Symptoms become apparent at the mean age of 11, with 90% individuals with Becker experiencing symptoms by age 20.1,5
- Progressive, symmetric muscle weakness usually starts affecting the proximal before distal limbs, and lower limbs before the upper limbs, often with calf hypertrophy and an increase in circulating creatine kinase levels, indicative of systemic skeletal muscle injury.1,3
- In individuals living with Becker, lower limbs are initially affected causing fatigue while walking followed by weakness standing up or waddling gait. Upper limb weakness may also be present and worsens as the disease progresses.3
- According to an analysis of the 162 UK BMD patients, the median age of those requiring assistance of crutches, walking sticks, another person or part time wheelchair use was ~40 years. 19
Over time, as muscle is replaced by fat and fibrosis, individuals living with Becker have difficulty standing up, walking (waddling gait), running and jumping, and may have frequent falls.3
Cardiac
Over 70% of Becker patients develop dilated cardiomyopathy, characterized by congestive heart failure and impaired left ventricular systolic function.11,12
- In Becker muscular dystrophy, deterioration of cardiac muscles is a result of contraction-induced injuries in the absence of fully functional dystrophin.13
- While dilated cardiomyopathy usually presents in the 3rd or 4th decade of life, typically years after the appearance of musculoskeletal symptoms, the risk of cardiomyopathy is independent of the skeletal muscle phenotype. Individuals with Becker can have minimal skeletal muscle weakness but advanced cardiac disease even before in their teens or 20’s.4,11,12
- If left untreated, cardiomyopathy can lead to heart failure, even requiring heart transplantation. Heart failure is the most common cause of premature death in individuals living with Becker. 3,11,12,13
As soon as the diagnosis of Becker muscular dystrophy is established, a comprehensive cardiac examination is recommended.3 Cardiac involvement in Becker is progressive and therapy is available. Cardiac examinations need to be regularly repeated.
Respiratory Complications
Weakness of the diaphragm and other respiratory muscles can result in the decline of respiratory function in individuals living with Becker muscular dystrophy.3
In those with advanced Becker muscular dystrophy, ventilatory support may be required.4
Other Symptoms
- Autism spectrum disorders, attention-deficit hyperactivity disorder, depression, anxiety disorders, and obsessive-compulsive disorder may also occur in individuals living with Becker.3,7
- Individuals living with Becker may also present with behavioral issues, panic attacks, and language problems.3,14,16
- The prevalence of intellectual disorders is 4 times higher in children and adolescents with Becker, than in the general population of the same age.3
- Becker muscular dystrophy can lead to gastric distention, gastroparesis, and secondary conditions including constipation, urinary incontinence, and pain.3,17
As the most frequently reported secondary conditions (i.e. not related to the skeletal, heart, and respiratory systems), cognitive and neuropsychological symptoms are observed in approximately 30% of individuals living with Becker muscular dystrophy.
