Becker Muscular Dystrophy (BMD)

Diagnosis

The diagnosis of Becker muscular dystrophy (BMD) may vary greatly. The symptoms can appear in early childhood, as early as age 5, or as late as age 60. Indeed, some of these patients don’t reach their developmental milestones and some find out that they can’t keep up during their physical education classes or during military training.¹

As in diagnosing any other form of muscular dystrophy, a physician usually begins by taking a patient’s and their family’s history, followed by an extensive physical examination. The history and physical examination can go a long way toward making the diagnosis, even before any complicated diagnostic tests are done.

A doctor wants to determine whether a patient’s weakness results from a problem in the muscles themselves or in the nerves that control them. Problems in the muscle-controlling nerves or in motor neurons (which originate in the spinal cord and brain and reach out to all the body’s muscles) can cause weakness that looks like a muscle problem.

Other diseases have some of BMD’s same symptoms. BMD has sometimes been misdiagnosed as Duchenne muscular dystrophy (DMD) or limb-girdle muscular dystrophy (LGMD). For this reason, it is important to go through a careful diagnostic process, usually involving genetic (DNA) testing.

Early in the diagnostic process doctors often order a special blood test called a CK level. CK stands for creatine kinase, an enzyme that leaks out of damaged muscle. When elevated CK levels are found in a blood sample, it usually means muscle is being destroyed by some abnormal process, such as muscular dystrophy or inflammation. Therefore, a high CK level suggests that the muscles themselves are the likely cause of the weakness, but it does not tell exactly what the muscle disorder might be. In BMD, CK levels, for affected males, are usually elevated above normal levels — up to five times the upper limit of normal levels or more. For carrier females, CK levels can vary between twice the normal concentration and up to 10 times the normal concentration.²

Electromyography, a test that involves delivery of electrical impulses through special needles inserted in the affected muscles and measurement of the conduction of these electrical impulses, may be ordered by the doctor in some cases of suspicion of BMD.

DNA testing of the dystrophin gene to diagnose BMD is now widely available and is usually done from a blood sample. In many cases, the DNA test alone can tell families and doctors with a high degree of certainty whether the disease course is more likely to be BMD or DMD. Genetic testing is indicated in patients with high levels of CK and suggestive signs or symptoms of BMD (or DMD). When a mutation in the DMD gene is identified, the disease is confirmed.

Overall, there are two approaches for genetic testing. The first one is analysis for deletions/duplications, which are the most common form of mutations, seen in 70% to 80% of cases. The second approach is the scanning and sequence analysis of point mutations using multiple available methods.

You can ask your MDA Care Center physician or genetic counselor what tests are available. For more on getting a definitive genetic diagnosis, see The Genie's Out of the Bottle: Genetic testing in the 21st century.

Female relatives of men and boys with BMD can undergo DNA testing to see if they are carriers of the disease. If they are, they have a 50% chance to give birth to children who are themselves carriers or who will develop BMD.

To view a presentation by a genetic counselor, see the August 2012 video Genetics of BMD: Why Your Mutation Matters.

In some cases, to be more certain about the disease and its course, a doctor may suggest a muscle biopsy in which a small sample of muscle is taken for special examination. Most patients are diagnosed by molecular genetic testing without undergoing muscle biopsy because muscle histology for BMD is not specific. Muscle biopsies show fibrosis and fat tissue instead of muscle tissue, as well as signs of degeneration, regeneration, and muscle fiber hypertrophy (enlargement of the muscle fibers).^3,4,5 Special staining in the muscle biopsy and dyes using antibodies for the detection of dystrophin may be used in case of a negative genetic testing.

Western blot, a technique for quantifying proteins, may be used in diagnosis as well. Western blot may be used for prediction of severity of the disease: In males, dystrophin levels between 5% and 20% of normal correlates with an intermediate phenotype (mild DMD, or severe BMD). Levels of 20% to 50% of normal dystrophin, or 20% to 100% of abnormal dystrophin, are related to mild to moderate BMD. A level of 0% to 5% of dystrophin indicates DMD.²

References

1. 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
2. Darras, B. T., Program, N., Miller, D. T. & Urion, D. K. Dystrophinopathies - GeneReviews - NCBI Bookshelf. GeneReviews, Seattle (2018).
3. Peverelli, L. et al. Histologic muscular history in steroid-treated and untreated patients with Duchenne dystrophy. Neurology (2015). doi:10.1212/WNL.0000000000002147
4. Bell, C. D. & Conen, P. E. Histopathological changes in Duchenne muscular dystrophy. J. Neurol. Sci. (1968). doi:10.1016/0022-510X(68)90058-0
5. 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