Diagnosing Becker Muscular Dystrophy (BMD) is not always straightforward. The age of onset and the severity of symptoms can vary dramatically, appearing as early as 5 years old or as late as 60. Some individuals may experience developmental delays in their early years, while others might only notice difficulties during physical activities like sports or military training. Accurate and timely diagnosis is crucial for effective management and care.
The diagnostic journey for BMD, like other forms of muscular dystrophy, typically begins with a detailed medical history of the patient and their family, followed by a thorough physical examination. These initial steps are invaluable and can significantly guide the diagnostic process, often even before more complex tests are conducted.
One of the first things a physician needs to determine is the origin of muscle weakness. Is it stemming from an issue within the muscles themselves, or is it related to problems with the nerves that control muscle movement? Weakness that mimics muscle disorders can arise from nerve-related issues or motor neuron problems, which originate in the spinal cord and brain and extend to all the muscles in the body. Distinguishing between these possibilities is a key early step in Bmd Diagnosis.
It’s also important to note that several conditions share symptoms with BMD. In some instances, BMD has been initially misdiagnosed as Duchenne Muscular Dystrophy (DMD) or Limb-Girdle Muscular Dystrophy (LGMD). Therefore, a careful and comprehensive diagnostic process, often involving genetic (DNA) testing, is essential to ensure an accurate BMD diagnosis.
One of the initial diagnostic tests doctors frequently order is a Creatine Kinase (CK) level blood test. CK is an enzyme that leaks out of damaged muscle tissue. Elevated CK levels in the blood usually indicate muscle damage caused by an abnormal process like muscular dystrophy or inflammation. While a high CK level suggests a muscle-related issue, it doesn’t pinpoint the specific muscle disorder. In males with BMD, CK levels are typically elevated, often reaching five times the normal upper limit or even higher. In women who are carriers of the BMD gene, CK levels can also be elevated, ranging from twice the normal concentration up to ten times the normal concentration.
Electromyography (EMG) is another test that may be used when BMD is suspected. EMG involves inserting special needles into affected muscles to deliver electrical impulses and measure how well these impulses are conducted. This test can help assess the electrical activity of muscles and nerves.
However, the definitive diagnosis of BMD often relies on DNA testing of the dystrophin gene. Genetic testing for BMD is now widely accessible, usually performed using a blood sample. In many cases, DNA testing alone can provide families and doctors with a high degree of certainty about whether the condition is more likely BMD or DMD. Genetic testing is recommended for individuals with elevated CK levels and symptoms suggestive of BMD (or DMD). Identifying a mutation in the DMD gene confirms the diagnosis of a dystrophinopathy, and further analysis can distinguish between BMD and DMD.
There are primarily two approaches to genetic testing for BMD diagnosis. The first, deletion/duplication analysis, detects the most common types of mutations, accounting for 70% to 80% of cases. The second approach involves scanning and sequencing for point mutations using various available methods. Consulting with an MDA Care Center physician or a genetic counselor can provide information on available genetic tests and the most appropriate approach for individual cases.
Female relatives of males with BMD can also undergo DNA testing to determine if they are carriers of the BMD gene. If a woman is a carrier, there’s a 50% chance that her children will either be carriers or develop BMD. Genetic counseling is crucial for families affected by or at risk of BMD to understand inheritance patterns and reproductive risks.
In some situations, a muscle biopsy might be recommended to gain further certainty about the diagnosis and the disease’s progression. A muscle biopsy involves taking a small muscle sample for detailed examination. While most BMD diagnoses are made through molecular genetic testing, muscle biopsies can be helpful in cases with inconclusive genetic results or to assess the extent of muscle damage. Muscle biopsies in BMD typically show fibrosis and fat tissue replacing muscle tissue, along with signs of degeneration, regeneration, and muscle fiber hypertrophy (enlargement). Special staining and antibody dyes to detect dystrophin in the muscle biopsy can be used if genetic testing is negative or inconclusive.
Western blot, a protein quantification technique, can also play a role in BMD diagnosis and prognosis. Western blot analysis can help predict disease severity by measuring dystrophin levels. In males, dystrophin levels between 5% and 20% of normal are associated with an intermediate phenotype, which could be milder DMD or more severe BMD. Levels between 20% and 50% of normal dystrophin, or 20% to 100% of abnormal dystrophin, are linked to mild to moderate BMD. Very low dystrophin levels, ranging from 0% to 5%, are indicative of DMD.
Accurate BMD diagnosis requires a multifaceted approach, integrating clinical evaluation, blood tests, genetic testing, and in some cases, muscle biopsies and Western blot analysis. This comprehensive diagnostic process is essential for distinguishing BMD from other neuromuscular conditions and ensuring appropriate care and management strategies are implemented.
References
- Bradley, W. G., Jones, M. Z., Mussini, J. -M & Fawcett, P. R. W. Becker-type muscular dystrophy. Muscle Nerve (1978). doi:10.1002/mus.880010204
- Darras, B. T., Program, N., Miller, D. T. & Urion, D. K. Dystrophinopathies – GeneReviews – NCBI Bookshelf. GeneReviews, Seattle (2018).
- Peverelli, L. et al. Histologic muscular history in steroid-treated and untreated patients with Duchenne dystrophy. Neurology (2015). doi:10.1212/WNL.0000000000002147
- Bell, C. D. & Conen, P. E. Histopathological changes in Duchenne muscular dystrophy. J. Neurol. Sci. (1968). doi:10.1016/0022-510X(68)90058-0
- Desguerre, I. et al. Endomysial fibrosis in duchenne muscular dystrophy: A marker of poor outcome associated with macrophage alternative activation. J. Neuropathol. Exp. Neurol. (2009). doi:10.1097/NEN.0b013e3181aa31c2
