John Brandsema, MD, leads the discussion on the 5 main types of spinal muscular atrophy and the evolution of disease classification.
John Brandsema, MD: Hello, and thank you for joining this NeurologyLive® Peers & Perspectives® presentation titled, “Treating Spinal Muscular Atrophy.” Today we are going to discuss a number of topics pertaining to the diagnosis and treatment of SMA [spinal muscular atrophy]. I am Dr John Brandsema, neuromuscular section head at the Children’s Hospital of Philadelphia, in Pennsylvania. Joining me today is Dr Julie Parsons, professor of neurology, from the Children’s Hospital Colorado in Aurora. Thank you so much for joining us, Julie, and thank you to the audience. Let’s begin.
SMA, in natural history, has been classified as having 5 main types. The original classification is based on the time of presentation and the level of weakness at time of presentation. Unfortunately, the most common type is type 1 SMA, which tends to present in patients before 6 months of age with weakness that is quite progressive. These patients usually have a life expectancy of less than 2 years of age, unless feeding and breathing are fully supported. We then have a very severe prenatal-onset type of SMA, called type 0, implied when a patient is having symptoms at birth of SMA, which is often now grouped together with type 1. This comprises roughly 60% of patients with SMA. The remainder are patients with a milder phenotype: we have those who sit but never walk, and they are defined as having type 2 SMA. Then, we have walkers, who may achieve walking early in life, but may eventually lose that ability over their lifespan, labeled as having type 3 SMA. Finally, there is a type 4 adult-onset type disease, which can mimic other neuromuscular disorders, such as amyotrophic lateral sclerosis. I am curious, Julie: how has your thinking about the natural history of the classification of SMA been changing now that we have targeted treatments for this disease and the phenotype evolves as people are on therapy? How would you approach classifying patients now that they are on treatments?
Julie Parsons, MD: I think that is such a good question, John. I am not sure that things are that clear, really. When the new consensus guidelines came out, as you know, for SMA, the classifications changed from what we learned in medical school, with type 1 SMA being called Werdnig-Hoffmann [disease], which was, as you described, the severe phenotype. The new classification system consists of nonsitters, sitters, and walkers. That is interesting in terms of the level of function and, I think, gives us information in terms of what we expect from a motor standpoint with these patients. The confusing thing and the piece that we miss, if we’re just saying, “This patient is a sitter, or this patient is a walker,” is the genetic piece. The copy numbers of SMN2, for me, end up being another very important part of that classification. If we have, for instance, a patient who has, going off the old classification, type 1 SMA, the most severe phenotype, and they are a 2-copy patient, I know a little about what I would expect. The issue, as we will discuss, with some of the treatments is that those patients with 2 copy numbers may now be sitting or actually even walking. I think this is an area that is so confusing in terms of being great about classification. We need more words to describe the patients, rather than fewer words.
John Brandsema, MD: I would completely agree with that. We are starting to think of patients as nonsitters, sitters, and walkers with SMA, but these are fluid categories. Somebody may have been conceptualized as a nonsitter-for-life, initially, but now on treatment is becoming a sitter or walker as you’re saying. That phenotype is so different than somebody who initially achieved walking and then was stable for a long time in the natural history of the disease. The different manifestations of how they experience their SMA are so unique to each individual person, depending on how severe their symptoms were when they first presented, how soon they were able to get treatment, and what their response to treatment was like. When we think of some of our classical areas where we tend to need to support our patients, of course, we are always trying to optimize function with our physical and occupational therapy colleagues and orthopedic colleagues. As we get into more of the severe types of SMA, we tend to see respiratory involvement: this is the swallowing impairment, the need for feeding supplementation, and the breathing issues that can often be life-threatening for patients with the severe forms of SMA.
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Transcript Edited for Clarity