Muscular dystrophies are genetic disorders that involve progressive muscle wasting and muscle weakness. The muscle degenerates over time, which leads to the muscle weakness.

DMD and BMD are caused by similar genetic processes. Duchenne Muscular Dystrophy is the most common form of muscle disease. It is caused by a genetic alteration on the X chromosome, which is a deletion in 60% of the cases. The phenotype is not related to the size of the deletion. The milder phenotype associated with BMD is related to the fact that the genetic mutation generally maintains the reading frame, where as in DMD, the reading frame is out of frame. However, this in frame/ out of frame phenomena does not explain all cases of DMD/BMD. Most cases of DMD and BMD only affect males, because they only have one X chromosomes.

BMD is a milder form of DMD with a later age of onset. The course of BMD is slower, but less predictable than DMD.

In the early stages of DMD and BMD, the muscles affected include: pectoral muscles, trunk muscles, and muscles of the upper and lower legs. The weakness in these muscles lead to difficulty in maintaining balance, in rising and climbing stairs. Children with DMD are late in learning to walk. They often have pseudohypertrophy and may appear to be clumsy. Children may demonstrate the “Gower’s maneuver.” When they reach school age, they may walk on toes or balls of feet and assume a lordodic stance to compensate for their muscle weakness and help maintain balance. Some children with DMD have difficulty raising their arms. They may lose the ability to walk between the ages of 7 and 12. By early teens, the heart and respiratory muscles may be affected.

In BMD, adolescents usually begin to walk with a waddling gate, and they stick out their stomach. They develop weakness in the hips, pelvic area, thighs and shoulders. Often, individuals with BMD are in wheelchairs by the third decade or later. BMD is often misdiagnosed as LGMD or SMA.

DMD and BMD are heterogeneous. This is related to the amount of dystrophin protein that is present in the muscle cells. In DMD, there is no dystrophin present, while the presence of some dystrophin protects the muscles of those with BMD from degenerating as badly or as quickly as those with DMD. Some people with BMD have only mild skeletal muscle problems but severe cardiac complications. It is important that patients with BMD have their heart checked regularly and treated when necessary. Heart transplants have been performed in the past for individuals with advanced heart problems, but minimal skeletal muscle problems.

Medical advances through the years have lead to numerous therapies that are available to help children with DMD and BMD, such as special assistive devices and steroids. Contact the Muscular Dystrophy Association for more information.

Ways a person gets DMD or BMD:

1. A mother with a dystrophin gene mutation on one of her two X chromosomes passed on the gene to her son. (This occurs in approximately 2/3 of the cases.)
2. A sporadic mutation. (This occurs in approximately 1/3 of the cases.)
3. Germline mosaicism, a very rare genetic phenomenon. (In 5-15% of cases of affected sons where the mother is tested and a mutation cannot be found, germline mosaicism is present.)
   

   * The mutations that occur in the dystrophin gene are not random. There are hotspots at the 5' end of the gene and in the central region of the gene.

• Serum CK is very elevated
• Troponin I is elevated above normal but not to levels in cardiac ischemia
• Liver enzymes show high AST & ALT
• Schedule a muscle biopsy
• Endomysial fibrosis
• Variable fiber size: Small fibers rounded
• Dystrophic muscle
• Hypercontracted (opaque) muscle fibers
• Myopathic grouping
• Muscle fiber degeneration & regeneration
• Muscle fiber internal architecture: Normal or immature
• Dystrophin: Absent staining
• Other membrane proteins: Sarcoglycans and Aquaporin 4 are reduced
  
  

  Figure 1.

  Figure 1, which shows the pathological changes that define muscular dystrophy, is adapted from Obrien, K. F., and Kunkel, L. M. Dystrophin and muscular dystrophy: past, present, and future. Molecular Genetics and Metabolism 34, pp75-88 (2001). a. Hematoxylin and eosin staining of control tissue b. Hematoxylin and eosin staining of DMD patient, which shows abnormal variation in fiber size, degenerating and regenerating fibers, immune cell infiltration, and increased fibrosis c. Immunofluorescence analysis of dystrophin in control tissue biopsy d. Immunofluorescence analysis of dystrophin in a young DMD patient biopsy, illustrating the loss of sarcolemmal staining in DMD

  
  

• 96% with frameshift mutation (60-65% are caused by deletions)
• 30% are new mutations
• 10% to 20% of new mutations are gonadal mosaic

Some alterations are subtle changes in the DNA sequence in the dystrophin gene, such as point mutations. It is always most informative to test an affected individual first for a genetic alteration, and then proceed to test family members as necessary.

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