Current Series: Management of Duchenne Muscular Dystrophy

Amy D. Harper, MD: Becker muscular dystrophy is a muscular dystrophy that involves a protein called the dystrophin protein and typically it’s caused by gene changes in the DMD gene or the dystrophin gene. The primary difference between Becker muscular dystrophy and Duchenne muscular dystrophy is the amount of functioning protein or dystrophin that an individual has. Typically, with Duchenne muscular dystrophy being able to up the dystrophin protein is going to be less than 3%.  
 
If you are looking more at Becker muscular dystrophy, patients tend to have a larger amount of dystrophin protein. It’s not the normal amount, In fact, the protein is only partially functioning, but it still helps to make it a milder disease where even though this is a progressive muscular dystrophy, there will be some sparing when you have some dystrophin protein function... This allows the muscle membrane to be a little bit more stable, and the result is patients would walk for longer and have fewer effects from this underlying muscular dystrophy over time. 
 
The reading  frame rule is essentially in how do you make this protein. Typically for the out of frame mutations that you see in Duchenne muscular dystrophy, you are not able to make any of the dystrophin protein, but if there is just 1 little error within that frame of the gene or more of an in-frame mutation then this is where you get the partially functioning protein that is made, more of what you see in Becker muscular dystrophy. So the reading frame the way I talk about it in the clinic is thinking about the word cats. If you just have a C and a T, then you don’t know that that word is cat, But if you insert a small a then you kind of know it’s cat but it might not look exactly the same. The dystrophin  protein expression, if you look at it in the muscle, is going to help predict if this is a milder disease or a more severe disease 
 
Typically without treatment, we would expect a boy with Duchenne to begin showing signs of weakness and loss of ambulation somewhere between 8 to 12 years of age. With Becker muscular dystrophy, that typically occurs in the second decade, so a little bit later. They may continue to ambulate up until age 20 and then begin to have more difficulty. They both will still have cardiac effects, and so sometimes we are concerned about the cardiomyopathy more in Becker muscular dystrophy because they are more active and putting more strain on their heart due to the increased day-to-day activities. 

If you were able to increase the amount of dystrophin maybe as a therapeutic target for treatment, then you can lessen the severity of the disease and make it more Becker-like.  
 
There are dystrophin receptors in the brain, early on what you can see is that that child may have some motor, some speech delays and typically language development can be tied to learning. Often, speech delay with borderline motor development maybe the first signs that there is underlying Duchenne muscular dystrophy. The other impact of those dystrophin receptors would include having differences in learning, differences in attention. There is higher incidence of ADHD [attention-deficit hyperactivity disorder], obsessive compulsive tendencies, and differences in learning and how they process information. Therefore, the psychoeducational supports that are provided in the clinic are so important so they can be best supported in the school setting.