An overview of the diagnosis of spinal muscular atrophy, including prevalence, age of onset, and the role of genetic testing.
James Wymer, MD: As I mentioned, SMA [spinal muscular atrophy] is a spectrum disease. It presents with this motor neuron phenotype that will come out. They’ll primarily get the weakness; it will be pure motor with limited sensory. As it’s shown in this case, it can be proximal. There can be respiratory involvement with it, and there can be even clumsiness and tremors at times because of the way the motor neurons will be involved. There will be preserved sensation, so that will be 1 of the keys. In this case, that brings up the question of why they were initially called a muscular dystrophy because they were pure motor. But when that neurologist looked at them closely and saw the pattern of thinning of the muscles going on, I’m assuming that’s what was seen in this case. That leads you to the thought that maybe it isn’t so much muscle disease as it is the nerves going to the muscles, or the motor neurons. That’s going to direct you toward that question of, is this like spinal muscular atrophy?
When you’re seeing somebody like this, keeping in mind this can be at any age that they can present with more of this motor phenotype, you’re going to look at the differential. You may consider doing an EMG [electromyogram] nerve conduction study as a first step in the evaluation. What’s the EMG going to show you? It determines whether it’s primarily a muscle disease or more of a motor neuron disease. SMA is a typical pattern that shows chronic neurogenic changes will be present on it. That’s something that could be diagnostic.
Nowadays genetic testing is common because it’s easy to order as a next step to go right into a genetic test. That genetic test that you would do because of this pattern of weakness would likely be for the muscular dystrophies but also the SMA, because you want to cover all your bases. In this case, that’s what the neurologist was thinking at that time. It’s a pure motor syndrome with a mildly elevated CK [creatinine kinase], and everything is pointing toward the nerve. They said, “Let’s go into 1 of these genetic tests.” Ten years ago we would have done a muscle biopsy. We would have evaluated further. But now when they put that EMG with the exam, the CK, it points toward the SMA, and that’s what led to the genetic test. That’s what’s going to lead us to that genetic testing in this particular patient. But as an adult neurologist, in any patient I’m seeing, if I get that motor neuron description—clinical, where they’re appearing, where it became early in life, I’m going to think about doing the SMA in addition to any other testing.
We don’t have a good sense of the prevalence of adult-onset SMA. The reason why I say that is because it can be such a spectrum disease. In childhood, when they’re presenting with aggressive disease, it can be easier to diagnose. But as we get into the adult and you get people with milder and milder involvement, they can have a normal life span. They may just be a little slow and aren’t able to run as much as they were before. It can be a very mild disease. It’s not that common. There may be a couple per 100,000 that we will see, but the actual prevalence needs to be sorted out. Because with genetic testing, we’re learning more about the disease and the phenotypes that it can present. That gets us to a second question: What age will it usually present? That’s going to depend on how much involvement there is. When you look at the genetics of SMA, which is an interesting pattern in which you have the SMN1 and the SMN2. Depending upon the number of copies of SMN2 that you have, you can compensate for a deficiency in SMN1. If you compensate enough, it can present very late in life. As an adult neurologist, it’s something I think about in all the patients when I’m looking at a pure motor presentation with the weakness that we were describing in this patient. With genetic testing, it’s so easy to obtain. We will look to see if we can identify it.
Transcript Edited for Clarity