What is Becker's muscular dystrophy?

What is Becker Muscular Dystrophy?

Becker muscular dystrophy (BMD) is an X-linked genetic neuromuscular disorder caused by mutations in the dystrophin gene that result in production of a truncated but partially functional dystrophin protein, leading to progressive proximal muscle weakness with a later onset and milder course than Duchenne muscular dystrophy. 1, 2

Genetic Basis and Pathophysiology

• BMD results from mutations in the dystrophin gene located on the X chromosome, with the majority of cases (86%) involving in-frame deletions or duplications that allow production of reduced or abnormal dystrophin protein rather than complete absence 1, 3
• The dystrophin protein normally binds to actin at its N-terminus and interacts with the dystrophin-associated protein complex at its C-terminus, connecting the sarcomere to the extracellular matrix 1
• Approximately 67% of cases are inherited while 33% represent new mutations 1
• The specific mutation type significantly predicts clinical severity, with deletions involving exons 45-55 or exon 48 alone associated with later loss of ambulation compared to deletions of exons 45-47 3

Clinical Presentation and Age of Onset

BMD typically presents in teenage males older than 16 years of age, distinguishing it from Duchenne muscular dystrophy which presents before age 12. 1

Key clinical features include:

• Progressive generalized weakness primarily affecting proximal limb girdle muscles (shoulders and hips) with proximal weakness greater than distal 1, 4
• Calf pseudohypertrophy is a characteristic finding 1, 4
• Some patients exhibit only mild symptoms such as muscle cramps or isolated elevation of serum creatine kinase throughout their lives 4
• Gower maneuver may be observed, where patients cannot rise from the floor without using their arms to push up 1
• Cognitive or learning disabilities may be present in some patients 1

Diagnostic Approach

Serum creatine kinase (CK) levels are markedly elevated in BMD, typically exceeding 1000 U/L, and should be the initial screening test. 1, 4

The diagnostic algorithm proceeds as follows:

• Elevated CK concentration prompts molecular sequencing of the DMD gene for confirmation 1
• Muscle biopsy with immunohistochemistry or immunoblotting demonstrates a dystrophic pattern with abnormal dystrophin staining (reduced levels rather than complete absence) 1, 4
• Genetic testing identifies deletions or duplications of one or several exons in the majority of cases 4, 2

Cardiac Involvement

Cardiomyopathy is a critical feature of BMD and represents the most common cause of death, but can be prevented with specific treatment. 4, 2

Cardiac manifestations include:

• The vast majority of patients develop dilated cardiomyopathy (DCM) before their 20th birthday 1
• Progressive loss of functional myocytes leads to regional dysfunction followed by global dysfunction, though chamber dilation occurs only in late stages 1
• Elevated serum creatine kinase muscle isoforms are present, similar to X-linked dilated cardiomyopathy 1
• Female carriers can develop mild to moderate DCM in the fifth decade with slow progression 1

Natural History and Prognosis

Loss of ambulation occurs at a median age of 69 years based on Kaplan-Meier analysis, with only 13.5% of patients losing the ability to walk. 3

Disease progression characteristics:

• At last assessment (median age 26 years), 30% of patients exhibited left ventricular impairment and only 2.7% had respiratory involvement 3
• The phenotype is considerably more variable and milder than Duchenne muscular dystrophy 1
• Specific mutations predict outcomes: deletions of exons 45-55 and exon 48 correlate with later loss of ambulation and decreased odds of developing pathological left ventricular ejection fraction 3

Female Carriers

Female carriers of DMD mutations can exhibit clinical symptoms of variable severity, often milder and beginning later than in males, with cardiomyopathy being the most frequent feature requiring monitoring. 4, 2

Relationship to Other Dystrophinopathies

BMD exists on a phenotypic continuum with other dystrophinopathies:

• X-linked dilated cardiomyopathies linked to the DMD gene represent a phenotypic continuum of BMD 4
• Both BMD and Duchenne muscular dystrophy are caused by mutations in different regions of the same dystrophin gene 1
• The key distinction is that BMD mutations allow production of partially functional dystrophin protein, whereas Duchenne mutations result in complete absence 1, 5

Management Principles

A multidisciplinary approach is essential, with particular attention to cardiac monitoring and treatment, as cardiomyopathy is the primary cause of mortality. 4, 2

• Regular cardiac evaluation with echocardiography and ECG is mandatory 2
• Physical therapy to maintain mobility and prevent contractures 2
• Respiratory function assessment when clinically indicated 2
• Genetic counseling should be systematically offered to families 4