Philippa Cheetham, MBChB, MRCS, MD, FRCS: Hello and thank you for joining this NeurologyLive® CureConnections® on “Spinal Muscular Atrophy: Physician and Patient Management.” Spinal muscular atrophy describes a group of disorders that are associated with spinal motor neuron loss. The age when symptoms begin correlates with the degree to which motor function is affected. Recent therapeutic advances have led to exciting treatment options for patients, which we’ll be talking about today.
I am your host, Dr Philippa Cheetham, an attending physician at Mt Sinai Hospital in New York and today I am joined by Dr Crystal Proud, a board-certified pediatric neuromuscular neurologist at the Children’s Hospital of the King’s Daughters in Norfolk, Virginia. And also with me today is Sebastian Mills, who is going to share the details of his journey with spinal muscular atrophy and subsequent treatment with novel therapies. Thank you so much for joining us today. Welcome, Dr Proud, welcome, Sebastian, welcome to CureConnections®. Thank you so much for joining us today.
Crystal, we hear so much in the media about common diseases, cancer, heart disease, prevention, and educating patients about lifestyle issues. And yet, today, we’re talking about a disease that doesn’t get much attention. Many people have not even heard of this disease, spinal muscular atrophy. Can you tell us a little bit about this disease, how common it is, who’s affected by it?
Crystal Proud, MD: Certainly. So, spinal muscular atrophy is a condition that leads to a deterioration of the motor nerves throughout the body. And it is actually something that impacts about 1 in 10,000 children that are born. The carrier frequency is actually reasonably high, so 1 in 40 to 1 in 60 individuals are carriers of this disease. And it’s autosomal recessive, meaning that it takes to partners who are carriers to have a child that could be impacted by this diagnosis.
Philippa Cheetham, MBChB, MRCS, MD, FRCS: And so, this is a neurological disease?
Crystal Proud, MD: It is.
Philippa Cheetham, MBChB, MRCS, MD, FRCS: And in the title “spinal muscular atrophy,” we know it’s a medical term that means loss of. So, this is a diagnosis that affects the spine and the muscles. Can you elaborate a little bit more on how these patients present?
Crystal Proud, MD: Certainly. So, it impacts the motor nerves which sit in the spine. They sit in the front area of the spine. They send out projections to the muscles. And so, 1 body says I’m going to make a movement in my arm, the brain tells his anterior horn cells that are sitting in the spinal cord send that signal out through that nerve and move the muscle. In the patients that have SMA [spinal muscular atrophy], the health of that motor nerves it in spinal column deteriorates over time. In the reason for that is because these patients have a missing or mutated gene called the SMN1 gene and that gene is responsible for making the protein throughout the body that keeps these motor nerves healthy.
Philippa Cheetham, MBChB, MRCS, MD, FRCS: Now you’ve already mentioned that this is a genetic disease. It’s an inherited disease. And yet, 1 in 10,000, it’s not very rare but it’s also not a common disease. Is this something that can be routinely screened for? Is this something that families may be aware that it runs in the families? I mean, how we start evaluating, identifying these cases early on?
Crystal Proud, MD: That’s a really great question. So with some of the newer data that we have available about early treatment, which we’ll talk about more, we know that there is advantage to diagnosing and treating earlier. And so, many states are moving towards doing what’s called “uniform newborn screening.” So, every child that would be born in a particular state would be screened, evaluating whether or not they were impacted genetically by this diagnosis of SMA.
The states that do not have that up and running just yet would have children that would present throughout either infancy up into later childhood with things like weakness, loss of motor function over time, or failure to meet those expected motor milestones that we would typically see in childhood.
Philippa Cheetham, MBChB, MRCS, MD, FRCS: Right and you’ve already mentioned that this is a neurological disease. And there are many rare neurological diseases that primary care doctors may not see so commonly. Obviously, you’re a specialist working in this field who has seen these kinds of patients all day, every day. But, I would expect that some of the initial presentations are quite vague. And I guess a lot of patients present quite late after some of the warning signs that may be obvious to an expert like you may get missed by community pediatric doctors or primary care doctors. Is that what happens often?
Crystal Proud, MD: That’s incredibly true. The journey to diagnosis can be very long for some of our patients. I think that most people when going to medical school, hear about spinal muscular atrophy, they hear about the typical infant presentation, which is usually around the age of 3 to 6 months and infants comes in, is a floppy baby of 4 years had control, a weak cry, does not reach the ability to roll over or to sit up.
And those babies, I think, are a little bit more recognizable but still sometimes go unrecognized or recognized too late. It’s not uncommon for them to be sent to physical therapists and say “Well, let’s see if we can’t build that strength,” and probably the most appropriate thing would be to see the physical therapist to work on straight, but also see a neuromuscular specialist or a neurologist to be able to proceed with finding out why am I not meeting those milestones.
Philippa Cheetham, MBChB, MRCS, MD, FRCS: Right, right, and of course, there’s a huge spectrum in children’s development, even in normal spectrum, and I guess not all parents have children that behave the same, especially if it’s a first born. These early delayed milestones may not be so obvious to somebody that’s had other children as well.
Crystal Proud, MD: Exactly, so that’s where we rely on not only the lack of expected progression but loss. So many of the children that we see, no matter their age, will have lost the ability to do something or we’ll be having more trouble doing something that used to not be so hard. And there should be true red flags to be evaluated by a neurologist. I had a 9-month-old little girl who used to be able to crawl and was having more difficulty and began to actually lose the ability to crawl and then was becoming more unsteady with her sitting. That backtracking, that regression really should indicate that there is something greater that needs to be evaluated there.
Philippa Cheetham, MBChB, MRCS, MD, FRCS: And I guess for many parents where they’re comparing development with other children, for some there may be a sense of denial that my child is actually doing OK but it may not be as obvious to other people who see that there’s quite a lack you come across that sometimes, that parents are in denial that their child is not meeting the milestones that they should be?
Crystal Proud, MD: Absolutely. I think that there is a great optimism and hope. And we certainly perpetuate that in the clinic. But we also need to identify when there is a problem so that we can now intervene with a treatment. And so really, I consider this a true neurologic emergency. If this is on my list of possibilities—if this diagnosis is in my differential, I need to send testing quickly because treatment is going to need to be urgent.