IVDD & CDDY: Disc Disease in Dogs with Dr. Casey Carl, DVM

Watch Dr. Casey Carl, DVM, the Associate Medical Director at Paw Print Genetics, discuss IVDD & CDDY as well as answer your questions about disc disease in dogs!

Transcription

Monica DeBosscher [0:01] My name is Monica, and I’m on the Partnerships & Legal Affairs team here at Good Dog. In case any of you are new to Good Dog, our mission is to build a better world for our dogs and the people who love them by advocating for dog breeders, educating the public, and promoting canine health and responsible dog ownership. We’re a secure online community created just for dog breeders. We have a Legal Resource Center with sample contracts, special discounts for breeders (including $100 off each year for screening tests), and software built just for breeders to manage waitlists and your applications and keep records of your dogs and litters. We’re also completely free for breeders, so if you aren’t yet a member of our community, we invite you to learn more about our mission and apply to join us at www.gooddog.com/join. Now we’ll pass it to Dr. Mikel Delgado, our Standards & Research lead. 

Dr. Mikel Delgado [0:52] Thank you, Monica. Everybody, welcome to our webinar today with Dr. Casey Carl. Hopefully you’ve seen some of his previous webinars here at Good Dog. He always has amazing presentations. I learn so much from him. If you’re not familiar with Dr. Carl, he is a veterinarian who graduated from Washington State University in Pullman, Washington. He is now the Associate Medical Director at Paw Print Genetics. He’s been there for about 8 years. Just a wealth of information about canine genetics—always with the goal of bettering our breeding practices and improving the health of our canine companions. Today he’s going to be talking about Chondrodystrophy and Intervertebral Disc Disease and the risks and the genetic tests involved with that, and he’ll answer lots of your questions. So, without further ado, thank you and welcome, Dr. Carl.

Dr. Casey Carl [1:45] Hello, everyone! Thank you so much for joining me today. It’s so exciting to be here. I love working with Good Dog, and I’m excited to talk about this topic today because it’s a very, very hot topic right now in the dog world. There are still quite a few things that we don’t know in terms of the mutation involved with Chondrodystrophy and increased risk. But we’ll talk about what we do know and a whole lot of strategies about how to work with this and those types of things. 

[2:20] Today we’ll start out and talk a little about the inheritance pattern for Chondrodystrophy. It is a dominant risk factor, and we’ll talk about what that means. We’ll talk both about Chondrodystrophy as well as Chondrodysplasia, which is another similar condition that we also know has a genetic mutation that you can test for. In many laboratories, both tests are actually run at the same time, and we can talk about why that is and why that might be important. We’ll go into Intervertebral Disc Disease and talk about the two major types that we experience in animal medicine (at least in canine medicine) and what we may need to think about: how they differ and which one’s associated with a specific Chondrodystrophy mutation. We’ll talk about breeding and how that relates to the Chondrodystrophy mutation. We’ll talk just briefly about IVDD prevention and treatment as well. And then we’ll have a question and answer period. I’m sure there’s going to be quite a few questions. My hope is that I answer most of those questions in the course of this talk, but I’m very happy to stick around and answer questions if people have them, because this is a very hot topic for people right now. 

[3:30] First, before we start to get too far into this, I wanted to make a quick correction. In my last Good Dog presentation, I said something at the end of the presentation. As a veterinary professional, sometimes you collect all this knowledge and you don’t even know where you get it all from. I like to go back and watch previous presentations. I’m a pretty harsh critic of myself. But I go back and listen to these and see what was said. I heard myself say this in the presentation, and I thought: Where do I know that from? I do this quite often because you hear these things but you don’t always know exactly where it comes from. It could be from a variety of different sources. At the end of the presentation, somebody had asked about iris color in dogs, whether that could increase the risk of cataracts. At the time, I had mentioned that blue-eyed or albino individuals may be at greater risk of cataracts in old age. Come to find out: I was wrong. At some point that was thought. It was actually a pretty big thing that I had heard in veterinary school from a variety of different people, though I don’t have any obvious publications to back that up at that time. But it’s probably not true that blue-eyed or albino individuals have a greater risk of cataracts. In fact, there’s been at least 5 studies that have now been seen with a correlation between cataracts and brown eyes, not blue eyes, in people. And there was recently, in 2014 (I guess it’s not completely recent anymore), a study in blue-eyed horses showing that they also had a lower cataract risk with blue eyes. I just wanted to make that clarification. As a reformed perfectionist, these kinds of things drive me crazy, so I’ve been thinking about this a lot since the last time we talked. However, there was one interesting thing going back through it—it does still seem true, and this is something that I also heard in veterinary school: blue-eyed individuals may be at a greater risk for certain types of ocular cancer. Depending upon the particular individual, there may be various increases in risk for that. 

[5:35] Moving forward, the inheritance pattern that we’re going to be talking about today for Chondrodystrophy specifically is a dominant risk factor. 

[5:47] What a dominant risk factor means is that a dog only needs to inherit one copy of the associated genetic mutation from a single parent in order to have an increased risk of that particular disease, which also tells us that therefore at least one of those parents will also be at an increased risk for the same disease. You’ll notice the picture here of a Cavalier King Charles. I put some pictures here of dogs that have a fairly high frequency of the Chondrodystrophy mutation. We’ll talk a little more about that in a little bit here. There are some breeds where the Chondrodystrophy mutation is not going to be easy to eliminate because of the high frequency that it’s in. We’ll talk a little about that in some of these breeds.

[6:25] Just as a reminder, exactly how this dominant inheritance works… If you’ve seen any of my lectures in the past, I’ve shared these Punnett Squares. We have a situation here where we have one dog that has 1 copy of the genetic risk factor of a dominant risk factor here. In this case, we could say that dog has 1 copy of that Chondrodystrophy mutation here in Chromosome 12. We’ll dive into this a lot more. I just wanted to get a general understanding here before we dive into it deeper. And then there’s a dog here that does not have a copy of that particular genetic mutation, and it has 2 normal copies of the gene. We’ve denoted the normal copies of the gene by the capital A here, and then the dominant risk factor here by this D. We use our Punnett Square and pull in these particular copies of the gene. This helps us determine what we may expect from the offspring from this pairing. If we use a chart, pull in all of our different chromosomes from each dog, we find that roughly half the dogs overall (if we were to perform this breeding) would end up developing or being at an increased risk for this particular condition. The nice part, though, is that we do have about 50% of them that are going to be clear, which potentially we could use for future breeding if we wanted to eliminate that mutation. We’re going to go into this a little bit further in a bit, but I just wanted to remind people how this works. Another way to think about this as well is if a dog has 2 versions of the gene (it’s got a normal copy of the gene and it’s got a copy of the gene that’s got a mutation in it), it is going to give either one or the other to either one of the offspring. In this particular case, that would be a 50% chance for every offspring. That ends up working out to be about 50% of the overall litter as well that would have 1 copy. 

[8:19] First we’ll discuss a little bit about Chondrodystrophy and Chondrodysplasia and what these are. Basically, they are two genetic conditions that are associated with a change in the way that the bones grow and the cartilage surfaces mature on these bones. It decreases the length of the long bones or the growth of the long bones, causing them to be shorter. These two known genetic mutations are associated with what we refer to as a semi-dominant shortened limb in dogs. Semi-dominant is a little bit different than dominant. Semi-dominant means that if they inherit 1 copy (this is specifically only talking about the shortening of the limbs, not the IVDD risk), for each additional copy of these 2 mutations that you get, you’re actually going to have a greater decrease in leg length. Since we have two different locations that we’re looking at, and at each location in the genome we actually have 2 versions of that (1 from mom and 1 from dad), there’s 4 total copies of these mutations that we could get. As you progress from no copies of it up to 4 copies of it, you’re going to get a progressively shorter leg length. In addition to that, the Chondrodysplasia mutation, which is not associated with the IVDD, tends to have a greater impact on decreasing leg length than perhaps the Chondrodystrophy does. I’ll go into that a little bit more later, but I do talk to people that have dogs with just a single copy of the Chondrodystrophy mutation, and they often will say, “My dog doesn’t look any shorter than any other dogs.” In some cases, that may be true. They may not show a significant amount with just a single copy of that Chondrodystrophy, whereas it’s a lot more common with a Chondrodysplasia mutation that you will notice it. What has happened with this is that there’s a very particular location of a gene called the FGF4 gene. That’s located on Chromosome 18 in dogs. It’s been duplicated. It has been erroneously inserted into two different areas of the genome where it shouldn’t be located. One of those areas is in Chromosome 12. That is the location that’s responsible for what we refer to as Chondrodystrophy and also increasing that risk of IVDD. And then the same copied region has also been inserted into a different location in the same chromosome as FGF4 is actually located, in Chromosome 18. That is actually what’s responsible for what we refer to as the Chondrodysplasia.

[10:55] Here we have three different breeds, all with some level of limb-shortening. Over the years, breeders have identified dogs that have slightly shorter legs. They must have liked the way that those dogs appeared. Shorter legs were selected for many, many generations, due to these dogs’ appearance—without an understanding that maybe there could be a disease component to this. These three particular dogs are kind of interesting because they represent a different distribution of each of those mutations. We’ll talk about that here a little bit more in just a moment. 

[11:30] First of all, as we said earlier, an insertion in Chromosome 18 is associated with the cause of shortened limbs, which is semi-dominant, and that is referred to as Chondrodysplasia (CDPA). That semi-dominance is essentially an additive effect for every single copy of the mutation that you get. The same is true for the shortened limbs associated with Chromosome 12. Those have that similar effect on leg length. The one in Chromosome 12, again, is associated with the shortened limbs known as Chondrodystrophy (CDDY). It’s also associated with an increased risk of a particular type of intervertebral disc disease known as Type I. We’ll go into that here in a little bit as well, talking about the difference between Type I and Type II, which is another form that we commonly see in dogs. As I mentioned earlier, look at those three dogs that I showed earlier. Dachshunds are an example of a breed that has both the CFA12 and the CFA18 mutation. In fact, most Dachshunds (also most Corgis and a variety of other breeds that have incredibly extreme limb shortening) tend to have 2 copies of both of these mutations. Occasionally, we’ll see a dog that maybe has only 1 copy of 1 of them of something, but the vast majority of Dachshunds, Corgis, and those types of breeds have two copies of both of these, which give them their incredibly short stature. A lot of times, I’ll have people call me and say, “My dog has Chondrodystrophy mutation, but he’s not that short. He doesn’t look like a Dachshund.” This is the reason why. There’s actually more to the story. In addition to these 2 genetic mutations, there’s probably other unknown mutations, too, that also play a role in shortening legs in dogs. But these are the 2 major ones that we know now and can actually test for. Because of the fact that this Dachshund has the Chromosome 12 mutation, it predisposes the Dachshund to IVDD. They’ve always been the major breed, at least historically, that’s been looked at for back problems. It’s just been discussed a lot in the breed. But they’re definitely not alone in IVDD problems. 

[13:35] Here we have a Beagle! It also has slightly shorter limbs, but Beagles actually only ever seem to carry the Chromosome 12 (the Chondrodystrophy) mutation. For that reason, they too are predisposed to IVDD. They don’t need that Chromosome 18 mutation to be at a greater risk of IVDD. Because they don’t have that Chromosome 18 mutation, they also aren’t quite as short as some of the Dachshunds that we see. Lastly, we have the Norwich Terrier here, which is an interesting situation because this dog only carries the CFA18 mutation. A lot of Terriers carry this Chondrodysplasia mutation. There’s a lot of short-legged Terriers out there that carry this. Some do carry the Chondrodystrophy or CFA12 mutation as well. But a good portion of them carry the CFA18. Interestingly, the Norwich Terrier is not in a group of dogs that seem to be predisposed to IVDD. This is an example of a breed that doesn’t seem to have that increased risk, despite the fact that they have shorter legs. There are many other breeds out there like that. 

[14:42] We’ll get into it now with Intervertebral Disc Disease and exactly what it is. We can talk a little bit about the specific types as well. By the way, this is my dog, Spike, here. You’ve probably seen this picture before. I had it in some other presentations. This is him in Montana on the boat. He loves the sunshine. It’s his favorite place to be. It’s one of the few places where he actually minds his Ps and Qs. He’s a naughty boy. 

[15:09] So the role IVDD plays is important to understand as we talk about this disorder. Please excuse my poor art up here. I created this little diagram to try to make it a little bit easier to visualize what we’re talking about. Obviously we have a dog here. Each of these white rectangles represents the vertebrae that are going down along the spine and very exaggerated room between the vertebrae so we can see what’s going on. Each of these blue little ovals here that I added represents an intervertebral discs that lie here, just underneath the spinal cord and have several functions. But these intervertebral discs play a really important role in attaching all of the vertebrae together. It increases the skeletal stability in these dogs. It also provides for movement in all directions, including rotational movement of the spine and all the things that are necessary for dogs to be able to move around and do the things that they do. It plays a really important role in shock absorption. If a dog is to jump from a higher location, a lot of that force is transmitted to the spine. These intervertebral discs play an important role in trying to decrease that amount of shock going to the body. It also protects the spinal cord as well. There are two main layers to the intervertebral discs that we talk about. A distinction between these two is important when we’re talking about this disease because there are slightly different roles that each of these layers play in the two different types of intervertebral disc disease. The first (or outer) layer that we’re going to talk about here is known as the Annulus Fibrosus. This is a very tough fibrocartilage layer that forms the outside boundary of that and plays an important role in keeping that disc in shape. And then there’s also an internal portion of the disc that is a gelatinous or jelly-like center to that, which is actually a remnant to a developmental tissue. It has a very high level of what we refer to as Glycosaminoglycans (GAGs). This has a very high water content. I’ve heard of this gelatinous substance referred to as pressurized fluid. This Nucleus Pulposus plays a really important role in IVDD because a chance in the Nucleus Pulposus underlies some of the disease that we see. 

[17:43] First we can talk a bit here about Type II IVDD. This is a type of IVDD that’s most commonly associated with larger breed dogs and is related to age-related changes in dogs. Like all dogs, humans also do have this type of IVDD where, over the long-haul, we get a lot of wear and tear on joints, including the intervertebral discs in our spine. They become less flexible and more able to be damaged over time. That can end up resulting in these age-related changes that can result in this form of IVDD. It’s typically more common in dogs greater than 6 years of age. Obviously not every dog develops this. There probably are other genetic factors that play a role in how likely a dog may be to develop IVDD at all. But based upon a lot of the things they’ve done in their life and all of this other history, these dogs may end up showing these signs. It’s also associated with something we refer to as disc protrusion, or more of a bulging of the disc rather than a rupture of the disc. We’ll talk about that difference in Type I here. But this protrusion or bulging is an outer layer (that Annulus Fibrosus layer) into the spinal cord. The Nucleus Pulposus (or the inner version of that disc) does not rupture through and actually damage the spinal cord. Instead, it’s a general bulging of the disc that ends up occurring. Sometimes that can be due to the Nucleus Pulposus actually infiltrating some of the layers of the outer Annulus Fibrosus, but it doesn’t break through completely. It simply bulges, applying pressure to the spinal cord. Quite often these cases are chronic, and they quite often have recurring flare-ups that we see. I had a dog with this, and every few months or so she would have a flare-up where one of those discs would protrude a little bit more and up resulting in some inflammation. There was a period of time where we had to nurse her back into health again. There’s pain associated with it. There can be neurological dysfunctions. Sometimes that dysfunction can get a little more significant as the dog ages, after it’s had multiple of these events of protrusion. And there can be weakness in the hind end of these dogs, beyond the point of where that disc protrusion occurs, from there to the tail. In these cases, surgery is rarely indicated. There are situations where dogs can have surgery if they’ve had ongoing issues with this, and they think it will really improve the quality of life. There can be some surgeries that are done to this. But in general, it tends to be less frequent that we expect to see it in this type of old age range. This, again, can happen in any dog. It’s not necessarily associated with any specific genetic mutation that we know of or can test for at this time. But it’s something we see in a lot of old dogs. I saw a lot of old dogs with back pain in practice. If you just palpate along that spine in many dogs over 6, you will get some reaction in certain areas of the spine. 

[20:55] I blew up the diagram a little bit. I wanted to show what we’re talking about with this. Essentially what happens is we’re going to get that bulging. The Annulus Fibrosus, as I mentioned, is not broken. But it simply bulges and applies that pressure to the spinal cord there, causing some damage. Again, because of the fact that it doesn’t have more of an actual explosive rupture, these tend to be (in general) less severe in terms of the clinical signs than those dogs with the Type I IVDD. 

[21:25] Type I is the one we are really here to talk about more than anything. This is the one that is associated with the CFA12 insertion or that Chondrodystrophy mutation, as it’s often referred to. Dogs that have this mutation—they begin a process of intervertebral disc degeneration earlier than a year of age. There’s been evidence that suggests that these intervertebral discs are starting to undergo a process of change very early. It’s also known as Chondroid Metaplasia, where that inner Nucleus Pulposus that we talked about earlier is actually substituted with collagen. There’s a tissue substitution that goes on there that makes these discs over time be less pliable and less able to perform all of their jobs effectively than they once did. In addition to that, there’s also calcification that occurs in these discs as well. Both of these are signs of this condition occurring. There’s even been some studies looking at calcification in discs as well. Both of these are signs of this condition occurring. There’s even been some studies looking at calcification of discs as potentially an early precursor or prognostic indicator for IVDD. It does appear that dogs that show calcification in their discs do have an increased risk of potentially having that disc rupture at some point. It is something that sometimes can be looked at, but not all dogs will show obvious calcification on radiographs, though it is something that is commonly seen. This type of IVDD tends to occur in younger dogs. It can occur at any age, but the most common age that we would expect to see this is 3-7 years of age. Most of these disc ruptures with Type I also occur in what we refer to as the thoracolumbar region, or the region of the spine that is above the thorax or the abdomen—that area there is very common for these particular disc herniations to occur. They can occur in other areas as well. As we mentioned earlier, we talked about protrusion of that disc (or that bulging of that disc into the spinal cord) but when we’re talking about Type I IVDD, we’re talking about something that is often referred to as extrusion. It’s the extrusion of that Nucleus Propulsus or that center portion of the disc; it actually ruptures through the Annulus Fibrosus into the spinal canal. That can end up resulting in a variety of different problems. Severe acute pain is obviously one of them. There’s some very significant neurological dysfunctions due to spinal cord bleeding. Over a period of time, there can also be significant death of those nerve cells or neurons over the spinal cord, also resulting in additional problems. Weakness and paralysis are very common. We’ll talk in a little bit about how we treat these cases and things that we’re looking for—something referred to as deep pain is a really important prognostic indicator that veterinarians are looking for in these dogs. With this type, surgery is often indicated because of the fact that a fairly small percentage of dogs with this type of extrusion end up getting back to full health without this type of intervention. There are several ways to be able to correct these, but we’ll talk about that a little bit more here.

[24:49] Here we have the diagram again, this time showing a little bit more of what we would see for a Type I type of disc herniation, where that NP is actually going to break through that AF layer. This is often a very violent type of herniation, under a lot of pressure. That increased pressure can cause a lot of damage to that spinal cord—much more significant, typically, than we would see with the Type II, thus leading to the more severe clinical signs that we see. Again, this is all associated with that Chondrodystrophy or CFA12 mutation. 

[25:24] One of the biggest questions that I get asked when we get this result back—first of all, there’s always a little bit of shock and confusion for people that have never done this testing before, to get this back and see the results. In actuality, this mutation is fixed in some breeds in the sense that nearly every single dog of that breed type has 2 copies of the mutation. In those cases, we’re not likely to be able to actually eliminate that mutation from those breeds. Really the only way that would be possible is in situations where outcrossings to other breeds were performed to try to get in some dogs that have fewer copies of that mutation. In those breeds, unfortunately, it’s just going to be something that is not going to be able to be eliminated. 

[26:10] When we do have a situation where there are breeds that have fewer than 2 copies of it, we have an opportunity. We have an opportunity to try to eliminate the Chondrodystrophy mutation from the breed and thus lower our IVDD risks. But there are a couple of things that we have to really keep in mind. One (which is potentially the most important) is the potential loss of genetic diversity that can occur if we happen to remove every dog with this genetic mutation from breeding. We’ll talk about that in a moment and why that’s such an important consideration and why we really have to be cognizant of this, or else it’s going to cause a lot more problems for the breed down the road. The other thing is meeting breed standard leg length. There is some speculation that perhaps eliminating this mutation will increase leg length in dogs, specifically that Chondrodystrophy mutation I’m talking about here. Really eliminating either the Chondrodystrophy or Chondrodysplasia mutation might increase that leg length significantly enough to perhaps push a dog outside of a breed standard size. We’ll talk about that a little bit more here in a moment. It’s more theoretical at this point than actual in what I’ve seen. But I would not be surprised if there are some breeds that this may end up being an issue for, if they tried to eliminate this mutation. 

[27:28] First we’ll take a look at genetic diversity and why this is so important. We’ll talk a little bit about why this is so important, and we’ll talk about why eliminating every dog with the Chondrodystrophy mutation (especially in breeds where it’s found in high frequency) would be very unwise over the long term. Here I’ve set up this little diagram. On this left side here, we have a bunch of different individual dogs. They’re all different colors, indicating the genetic diversity that they have within them. At some point, this is a diagram representing something referred to as a genetic bottleneck. Genetic bottlenecks can occur at any time that a population is limited to some degree. In the case here, when we’re talking about Chondrodystrophy, we would exclude certain dogs from breeding because they have a specific genetic mutation. Well, it’s very similar to the effect that we would see in a population that, say, had a very severe infectious disease that may kill a large percentage of the population, leaving behind much fewer individuals to be able to carry on the genetics from that population going forward. In this case, you can see on the left here that we have all of these colors, representing that unique genetic diversity. But all these dogs now have been found to have a specific genetic mutation. We are going to eliminate all of these dogs from breeding, leaving a minimal amount of genetic diversity left behind. As we move forward, the population of that breed is repopulated. Only this minimal number of dogs has a small amount of genetic diversity compared to what the population previously had. In and of itself, that may not be terrible, but there’s a lot of consequences that come as a result of that. You end up getting a much less genetically diverse population, which means that all of the dogs are actually more closely related. When you have a dog that’s more closely related, not only does the new population share a lot of similar genetics that make them dogs, but they’re going to share half the possibility of sharing a lot of the same disease-associated recessive mutations, so mutations that cause disease that we may not even have a genetic test for. There may be something there. You may not see that very commonly in the population because it’s at a very low frequency in the population before the elimination of all this diversity. It’s possible that when we limit that genetic diversity, this may be found at a lot higher frequency. So, for example, I’ve placed these stars on dogs that are carrying an unknown recessive genetic disease mutation here. Most of those dogs have been eliminated, but the mutation still exists in the new population. And as they repopulate that particular breed with this new population, that specific mutation that previously was found only in rare dogs is now going to be found in perhaps a lot more of the dogs in that population, thus increasing the risk for that particular disease. We’ve solved our problem. Let’s say in this case, it is Chondrodystrophy. We’ve eliminated the Chondrodystrophy, but low and behold! A new disease pops up that we didn’t even know was circulating in the population because it was in such low frequency that the likelihood of getting two dogs together to produce affected offsprings was so unlikely then, whereas it is now more likely. In addition to that, it’s been well-documented that low genetic diversity within a population—not only does it increase the risk of recessive disease like we talked about here but it also ends up resulting in lower fertility rates, shortened lifespans in dogs, decreased litter sizes, and just a general decrease in overall health quality for a particular population. Anything we can do to maintain this genetic diversity is going to be really, really important over the long-haul for these breed clubs, especially in situations where a specific genetic mutation is found in high frequency, where we wouldn’t want to eliminate all of those dogs from breeding. 

[31:28] When we’re thinking about breeding strategies, we have to take into account the frequency of each mutation. Again, slow removal of this insertion would be preferable, over the long-haul, rather than eliminating every dog with the mutation for breeding. It would be preferable to maintain that high level of genetic diversity that we would really like to maintain. One way of doing that would be to keep these dogs in the gene pool if they have 1 or 2 copies of that Chondrodystrophy mutation and breed them back to clear dogs, if at all possible. That will decrease the number of copies in the offspring to some degree. For example, if you had a dog that only had 1 copy (and we will go into this a little bit more in a moment) and bred it to a clear dog (as we showed earlier), about 50% of those dogs would be clear. If you chose one of those dogs for future breeding prospects, then you could eliminate that. You didn’t have to eliminate all the genetic diversity that went along with that in that process. In some cases, you could even breed a dog with 2 copies of the mutation to a clear dog. In that circumstance, all of the puppies will be carriers of a single copy of the mutation, and they would still all be at risk for Chondrodystrophy, but doing that one more time and breeding one of those dogs back to another clear dog—in that second generation, you will start getting clear dogs again. It seems kind of counterintuitive to many people that we would think about doing this because we are going to produce some dogs that are going to technically be at-risk for the disease. Over the long-haul, it is going to be a much better practice in these breeds that have the high frequency of the mutation. Now, there are some breeds out there that have the Chondrodystrophy mutation at very, very low frequency. You could make an argument, in those cases, that maybe you don’t breed dogs with 2 copies of the mutation, and instead only breed dogs with 1 copy back to clear dogs. But a good portion of the dogs out there that have this mutation have it in fairly high frequency. This approach may be a better approach. If, for some reason, you can’t find a clear dog (you can find dogs that have only a single copy of the mutation) then another potential way to address this might be to breed 2 carriers, though it is less ideal in many circumstances to do that. About 25% of the dogs would be normal and have no copies of the mutation. You would get about 50% that would have 1 copy. They would still be at risk. And 25% would get 2 copies. Again, they would be at risk. One factor to consider, though, is that dogs with either 1 or 2 copies are believed (at least at this point) to have the same risk of developing IVDD. So having 2 copies (at least with the data we’ve seen so far) doesn’t appear to increase the overall risk of them actually developing the IVDD. We could potentially use this to our advantage to try to get at least some clear puppies that we could breed to move forward. 

[34:26] Again, we’re going to use these Punnett Squares. This is actually the same thing that we looked at in the first Punnett Square with just the Chondrodystrophy or CFA12 mutation being inserted in there, rather than the generic disease that we talked about earlier. If we followed the same process and extrapolate all of this out, we find that if we were to breed a dog with 1 copy of the Chondrodystrophy mutation to a clear dog, roughly about 50% of that litter would be clear. If we wanted to eliminate this, then we would pull a dog from that breeding from those clear dogs to use for future breeding. If we did this with a dog that had 2 copies of the Chondrodystrophy mutation and did the same thing, we would find that all of the puppies would end up having 1 copy of the mutation associated with IVDD. It would be all at-risk in that first generation. Again, taking one of those dogs and breeding it to a clear dog after this, in that next generation you would start seeing some clear puppies. 

[35:30] Here again is the situation where we have 2 dogs that each have 1 copy of Chondrodystrophy. Breeding them together would end up resulting in the breakdown here. Essentially, you’re going to get about half of the number of clear dogs that you would have gotten had you bred a dog with 1 copy to a clear dog. As we mentioned earlier, breeding a dog with 1 copy to a clear dog would end up resulting in about 50% of the litter being clear. In this case, if you’re breeding 2 carriers together, that drops down to about 25% of the litter, and 75% of the litter has at least 1 copy of the Chondrodystrophy mutation. Therefore, about 75% of the litter in this case would be at an increased risk for the IVDD. In some ways, this may even be preferable to breeding a dog with 2 copies to a clear dog because of the fact that you at least get some clear dogs from this pairing. 

[36:26] We also mentioned that we have to take into account leg length in dogs. There is at least a theoretical risk of dogs not meeting the breed standard length if we remove this Chondrodystrophy mutation. I will say that this is theoretical, but it is a possible concern for some breeds. I will say that I’ve been working with a lot of people now, over the last year or two with this. As of yet, I have not had a single client tell me that they have eliminated this mutation and the dogs now are beyond the breed standard size for their breed. I do think that it is possible that I will eventually hear this from someone, but up to this point I have not. Various breeds may be slightly different in how this can end up affecting them, in terms of their overall leg length, due to a variety of different factors (probably other genetic factors and things). It’s something to keep in mind. One proposed solution for that, though, has been found in breeds like these Poodles. Mini and Toy Poodles actually are known to carry the other mutation, the CFA18 mutation or the Chondrodysplasia mutation. The reason that this Chondrodysplasia mutation has also been included in a lot of the testing for Chondrodystrophy is that this mutation can actually be used again to shorten up the legs in dogs whose legs got too long when the Chondrodystrophy mutation was eliminated. You can actually breed dogs with the CFA18 mutation back into the gene pool and decrease that leg length again without increasing the risk of IVDD. It’s another way to get that slightly shorter limb—without having that additional worry about the IVDD. However, this is only going to work in some breeds. Not every breed carries the CFA18 mutation. But this is one that we see in a somewhat lower frequency in Poodles and can potentially be used in the Mini and Toy Poodles in order to do that, if necessary.

[38:17] We don’t have a lot of information on a breed-specific basis related to the Chondrodystrophy mutation and the increase in risk for IVDD. There are a lot of studies out there looking at the overall risk of IVDD in a variety of breeds, but they either don’t look at the mutation involved or they didn’t do an analysis to see if the Chondrodystrophy mutation may actually be playing a role. They may not make a distinction between the Type I and Type II IVDD. They may just say IVDD as a whole. There’s not a lot of data out there currently, really looking at the increase in risk just from this mutation alone. There are many other variables that are associated with IVDD. There are probably many other genetic variables that are out there that can increase risk and environmental variables as well that can increase risk. (We’ll talk about a couple of things that might play a role in that in just a minute.) There are very few statistics currently available, as I mentioned. One statistic that has been found: Dachshunds are a good example of a breed that always inherits the Chondrodystrophy mutation. A lot of people want to know: How likely is my dog to develop this disease? We don’t have that number for individual breeds. It’s going to vary significantly from breed to breed, depending upon all of these other factors. In Dachshunds—a breed that pretty reliably inherits 2 copies of the Chondrodystrophy mutation—they’ve been documented to show IVDD clinical signs, about 19-24%. They inherit 2 copies of the mutation. It’s hard to say if this will be similar in other breeds. In fact, we really don’t think it probably would be. But it just gives us an indication here, if nothing else, that not every dog that inherits the Chondrodystrophy mutation will develop disease, by any means. There have been a couple of breeds that have been looked at, 3 major breeds, in terms of the overall increase in IVDD risk due to the Chondrodystrophy mutation. This is in comparison to other dogs from the breed that don’t carry the mutation. In the Chihuahua there were 60 dogs looked at in one study. Chihuahuas that had the Chondrodystrophy mutation were about 5.5x more likely to develop the disease than dogs without the mutation. A small group of Bichon Frise (39) were looked at, and they were found to be about 10x more likely to develop IVDD when they had the mutation versus when they didn’t. Shih Tzu had about the same increase in risk: 52 Shih Tzus looked at and about 10x more likely. They did a larger number of mixed breed dogs in the same study and found that in the mixed breed dogs, they had about a 15x greater risk of developing IVDD, compared to other mixed breed dogs that didn’t have this mutation. Unfortunately, at this time, that is about it as far as the data out there that I’ve seen associated with the mutation. Maybe there’s something I’m missing, but for the most part, I think this is about all we’ve seen. 

[41:23] After people get the results back, one of the other things that they ask me about is, “What can I do? Can I prevent this from happening in these dogs? Can I try to make sure that my dogs don’t develop this?” There are some things that will definitely help. There’s nothing that’s going to be 100% preventative. One major factor is daily moderate intensity exercise. A lot of people have asked me, “My dog has the Chondrodystrophy mutation. Can I still allow them to perform in agility and do those kinds of things?” I would say, for the most part, yes! In fact, it may actually increase their chances of preventing IVDD. One of the proposed theories is that perhaps these dogs have much stronger back musculature that’s supporting that spine and preventing very significant movements of the spine that could result in disc herniation that might occur in dogs with weaker back muscles. They don’t support that as well. Another thing that’s frequently talked about in this is preventing animals from jumping up and down from high beds or high chairs or other high locations. In many circumstances, it’s been recommended to use either ramps or stairs to very high locations for these dogs, to try to prevent all that force from being sent down the spine when they jump off such a high location. However, there has been at least one study that showed that stair climbing in and of itself may be beneficial. In the past when I had worked with other veterinarians, many of them mentioned, “Don’t let the dogs go on stairs or anything.” That may be important for dogs that have a very significant rupture. In early stages of disease, you wouldn’t want them going up and down the stairs. But stair climbing in and of itself can actually be really beneficial to preventing IVDD before they show clinical signs. It may, again, be related to that strength and back muscle. A couple of caveats there are that I definitely think it’s important that these stairs are not slippery, especially in dogs that already have some compromise in the hind end or dogs that are kind of wild, like this dog might be here, taking a leap down the stairs. No stair jumping. There are some dogs that I’ve seen that absolutely terrify me, where they’ll leap 3 or 4 or 5 stairs to different locations. That is equivalent to jumping off a bed or a high sofa and would be concerning. For dogs that are just going to go from stair to stair, I actually think there may be some long-term benefit to doing that, to keep those muscles strong. Maintaining an ideal weight has also been discussed, though I will say in one study, they didn’t seem to find a strong correlation with weight even though the found a correlation with the exercise quantity. It stands to reason that if you exercise your dog, they may be more likely to maintain that ideal weight a little easier. If we’re decreasing the amount of weight or force that is projected onto that spine, that would most likely be beneficial in most cases. One study also showed that IVDD is less common in dogs that are neutered or spayed after 12 months of age. There was a slight difference in that with males and females. Males seem to have up to 2x greater risk of developing IVDD if they’d been neutered prior to 12 months of age. Females had about a 1.5x greater risk of developing IVDD if they were spayed prior to 12 months of age. I cannot find any evidence that any supplements are shown to be helpful for prevention. In fact, in one study, it was actually shown that dogs that had been taking glucosamine or chondroitin supplements were at an increased risk to develop IVDD. That is a little bit misleading because it’s possible that they could have been given those supplements because they already had some problems. This was from a survey that was taken. At this point, there haven’t been supplements that have been shown to prevent or decrease the overall risk. 

[45:27] In terms of treatment for IVDD, it’s all based upon the severity of things. In chronic cases or these cases or these cases that tend to be more likely to be the Type II IVDD (or in less severe clinical signs), it’s possible that medical management may be a reasonable option for you. Cage rest and reduced activity is an important piece of that. Cage rest, though, may not be absolutely necessary in these chronic cases. Many scientists that have studied IVDD (both in humans and dogs) have switched their thinking on this to some degree. While it is really important to keep these dogs on cage rest in the acute/severe phases of having a disc rupture, in some cases it may be more beneficial to actually get them out and participating in low impact activity (just to walk around the neighborhood, making sure they’re staying on a leash and not off-leash and running around during those times). Stay in motion and prevent any further muscle atrophy from occurring and those types of things. The mainstays of medical management are going to be pain medications, narcotics and anti-inflammatories. Muscle relaxers can be really helpful. It’s something that’s not prescribed (in my opinion) nearly enough in these dogs. I found, when I was in practice, that it can make a huge difference in the overall pain relief for these dogs. Quite often they have very significant muscle spasms associated with their disc ruptures.This can really make them feel a lot better. Over the long haul in these chronic cases, there’s also some drugs. Even in acute cases, people are using these as well—drugs that are referred to as neuromodulating drugs. One that comes to mind that is particularly common and often used in veterinary medicine is Gabapentin. Maybe some of you out there are also on Gabapentin or a similar drug for neurological pain or chronic pain. It’s something that sometimes is used in these dogs. Surgical management is definitely another component to treating IVDD as well. It tends to be reserved more for severe cases of IVDD but the main goal is to decompress the spinal cord and to remove the diseased disc material that’s causing the problem. Herniations, though, can occur at other sites after surgical correction has been performed at one location. You may get another disc rupture at a different location. It definitely happens, and that can be very defeating to owners, obviously, when that happens. In these cases of surgical management, cage rest and medications are incredibly important in both keeping that dog comfortable and to also play a role in that dog getting well. It can take weeks for these dogs to get fully back on their feet and feeling 100% and so this is all going to be an important part of that. The recovery rate can be anywhere from, say, 50-95% in these cases, as long as the dogs have not lost their deep pain sensation, as we talked about earlier. There is a particular test that veterinarians will do (physical exam findings) that can tell them whether it appears this dog has lost that deep pain. If they haven’t, then depending upon the severity, otherwise there’s about a 50-95% recovery rate. Sadly, too, definitely not a treatment but one of the outcomes quite often with IVDD (unfortunately) is euthanasia. It can occur for a variety of different reasons. One major reason is that loss of deep pain that comes from very severe spinal damage that can actually end up resulting in nerve cell death from a process known as myelomalacia, where the spinal cord will actually lose neurons in that pathway as they die. As I mentioned, that loss of deep pain sensation, less than 30% of dogs walk again if they’ve lost that (without surgery). It still is a pretty guarded prognosis after surgery as well. Sometimes people will decide they don’t want to put their dogs through that and may decide to opt for euthanaia due to quality of life, rather than pursuing a surgical intervention. Financial constraints are always a major role in that, because euthanasia obviously (sadly) is cheaper than surgeries. The surgeries for IVDD can be very expensive, and some people may not be able to afford those procedures. 

[50:00] That comes to the end of what I had prepared to talk about. I will keep these references up here. These are the people that have done a lot of this work, and I’ve taken a lot of their information for this presentation here. I’ll leave this up for a couple of minutes, if there’s anything there that you want to take a look at. Some of these are freely available on the internet. Other ones, you need to pay a fee to have access to. But some of these things are out there and accessible. In a couple of minutes here, after I’ve answered a couple of questions, I’ll switch slides because I’ve got some additional things on the next slide that you may want to see. There may be a discount code for testing, if you’re interested in trying to get any of this testing at Paw Print Genetics.

Dr. Mikel Delgado [50:40] Great! Thank you so much, Dr. Carl. We are going to answer some questions! We got quite a few during your presentation, and people have been sending questions ahead of time, so we will do our best to answer them. Some of the questions are very similar. A lot of people want to know if their dog has one of the variants or if they’re a carrier, how do they decide if that dog should be bred? I think you addressed it to an extent, but if you could…

Dr. Casey Carl [51:15] If they have 1 copy of the mutation or even 2 copies of the mutation, if they are good breeding prospects otherwise, I think it would be best practice (as I mentioned) in most breeds, especially those breeds that have a relatively high frequency of this mutation, to keep them in the gene pool and breed them to clear dogs if at all possible. That’s going to be a much better approach. Keep that genetic diversity high in the breed. Again, prevent all of those other potential problems we could have in the long-haul when we lose that genetic diversity.

Dr. Mikel Delgado [51:44] Someone wants to know if there are symptoms to watch for, such as a lower than usual tail carriage, that could be indicative of early stage disc disease.

Dr. Casey Carl [51:53] There can be, especially in the cases of the Type II. Quite often with the Type I cases, you may get a little bit of a hint prior to a full-blown disc rupture there from time to time that maybe that dog is showing some signs of some back pain, but it’s not terribly uncommon for a dog to just have that major rupture as the very first clinical sign that we see in that dog, and them just go down acutely having issues. Dogs with the Type II variety—there are a host of things you can see. They can be anything from being incredibly nebulous, like a dog just going off food and just not acting right because they’re in significant pain. Dogs have a hunch in their back, showing that maybe they’re in pain. Maybe not getting around as easily as they once did. Just overall not seeming quite right. Sometimes it’s not incredibly obvious until somebody gets in there and really palpates along the spine and determines that they have some pain. It’s pretty hard to ignore the major ruptures. They’re going to be very obvious. But sometimes it is a little more tricky with the chronic ongoing things to know exactly how much pain your dog might be in at a given time. Sometimes they will be pain-free, and other times they may have some pain. Sometimes dogs are pretty stoic, depending upon the breed. My little guy at home—he stubs his toe, and it’s all over. But there are many breeds out there that are very tough and would not let you know too much about how they’re feeling. Sometimes it is a little bit tricky. But if you notice a significant change in behavior (maybe they go off food for a while, those kinds of things), it would be a potential concern—especially in these breeds that are known to be at risk. It might be something for the doctor to focus on when you take them into the veterinarian. 

Dr. Mikel Delgado [53:35] There’s a couple of questions about screening. What’s the best screening tool to decide if you should use a dog in your breeding program? It sounds like you give them some good parameters for keeping the genetic diversity in the program. Someone else also asks: Can X-rays be taken and correctly evaluated for higher risk dogs with IVDD, especially in Dachshunds?

Dr. Casey Carl [53:56] Dachshunds are one of the breeds where there has been some work at looking at X-rays or radiographs and looking for that calcification in the disc. It has been known that dogs that do have those calcifications in the discs do have an increased risk for IVDD. By no means is it a slam-dunk diagnosis. There are going to be many, many dogs that have calcified discs and never end up actually having a full-blown disc rupture that causes them significant problems. There’s nothing that is an absolute. I have heard of some people using radiographs as a guide for them and going to see if maybe the dogs have calcification as they do, maybe making different decisions. I guess somebody could definitely make an argument for that. But overall there’s no big foolproof methods of screening these dogs, unfortunately, to know they’re absolutely not going to produce an IVDD dog or they’re not going to develop it at some point themselves. There’s just nothing that can tell us that, unfortunately. 

Dr. Mikel Delgado [55:00] The dog who does develop it, would that change your recommendations as far as breeding? 

Dr. Casey Carl [55:05] That’s a good question. It could. There is some evidence to suggest in Dachshunds that perhaps over the years, Dachshunds had been selected for a decrease in IVDD risk because it was so well-documented in the breed that this was a potential problem. People decreased the breeding of dogs that had known back issues. I think that there’s something to be said for that, because it is possible that over the long-haul, you may be changing their genetic factors that also contribute to IVDD. Even though a breed may have the Chondrodystrophy mutation within their lines, if we stopped breeding dogs that were actually affected, then that might help in the overall incidence of this. The catch is that many of these dogs don’t develop IVDD until 3-7 years of age, when they were already bred. By that time, you may not actually know, at that 2 years of age or when you’re doing breedings that this dog will develop it in the future. That’s very tricky, and nearly impossible to predict. It’s not as easy to do that. Let’s say your dog had its first disc herniation at 2 or 3, and you hadn’t bred that dog yet—I could probably make an argument where maybe it’s better not to breed that dog because you know it seems to be at a greater risk, obviously. 

Dr. Mikel Delgado [56:35] Someone wants to know: Why are we testing Standard Poodles for IVDD? Does it come from breeders mixing Standards with Mini Poodles?

Dr. Casey Carl [56:42] There are very Standards that actually carry this. A small amount do. My suspicion—and there have been some Standard Poodles that have been documented with this at a very low frequency—is that maybe some of the data that’s out there on Standard Poodles is actually in Moyens because Moyen Poodles (which are the medium-sized Poodles, for those of you that may not know) were originally supposed to be down-sized Standards. My assumption is maybe if they didn’t have Moyen Poodles to select—like, if an owner was selecting a breed for their particular dog when doing the testing, they may have selected Standard Poodles. We at Paw Print Genetics have added this particular test to all breeds originally, just as an additional test for all breeds. But we are actually going to be making some transitions. I think we are going to be limiting the number of breeds now that we’ve collected more data. There are just some breeds that this doesn’t seem to be a factor in at all, and we’re probably going to eliminate this mutation in those breeds here in the near future. I’m actually putting together a list right now of the breeds that we’ve seen this in, from both the publications as well as in our own laboratory. We’re going to try to make a more specific effort to try to target those breeds as opposed to putting the test on every single breed. It was mostly due just out of a lack of knowledge as to which breeds could potentially be a concern. 

Dr. Mikel Delgado [58:11] We’ve got just a minute or two left. Is there any information or research on how many dogs with 2 copies of the IVDD mutation will become symptomatic? You said that stats are lacking.

Dr. Casey Carl [58:21] As I mentioned, there’s currently very little data to help us with that. It does appear, again, that whether they have 1 or 2 copies, the risk seems to be the same. In individual breeds looking at the risk associated with just the CFA12 mutation right now—not great risk calculations for specific breeds. Overall, as I said, it’s somewhere between 5-15x greater risk in the very small number of breeds that have been looked at, including mixed-breed dogs. Overall, that is an increase in risk. If a dog without the mutation has, say, only a 0.1% chance of developing IVDD, by having the mutation, their overall increase in incidence may not actually go up that much. It may only go up to 0.5%, even still less than 1%, let’s say. You may have other breeds without the mutation. They may already be at a more substantial risk, say a 5% risk of developing IVDD without the mutation. They may end up having a 25% risk if they have the mutation. Over time, I’m hopeful that more data is going to come out on this, and that we’re going to have a better understanding of it. We know it multiplies their risk. The dogs that don’t have the mutation—whatever their risk is is an important factor to consider. In most cases, we don’t have that yet. 

Dr. Mikel Delgado [59:51] Great. I want to respect your time and our audience’s time. Thank you for being here, for a fantastic presentation, and for answering all of our questions. It sounds like you have one slide you’d like to review?

Dr. Casey Carl [1:00:06] I just wanted to get this out there. This is the Good Dog coupon code that we have there, that GDOG21, all one word, all caps. You can put it on there. It’ll give you 40% off any order. If you happen to order a full disease panel for any dog, it’ll get 50% off of the testing for that particular dog. I also have my contact information here as well. Please feel free to send me an email if you have any questions, or even give me a call at that phone line there during our business hours. I’d be very happy to chat with you on the phone. I do that all the time and really enjoy getting to know our clients and learning about their programs. Also, I’m on Facebook. This is my work Facebook page. I won’t blast you with a whole bunch of advertising or anything. I do occasionally send out information about our sales that we have going on, but I’m not going to hit you with a whole bunch of things. More than anything, I just want to be a resource out there. It’s another way to reach me. You can just send me messages through Facebook if you’d like. I answer a lot of messages on there to a lot of our clients. A few of our clients are still on Facebook. Happy to help there! Big thank you to Good Dog, as always. A class act. Just a great group of people to work with. I couldn’t be more thrilled to work with them. I love what you guys are doing for dogs. I love that the standards are being elevated for dog breeding. Thank you to all of you listening today. It definitely shows that you are in that group, caring enough to sit here and listen to me babble on for an hour. You’re definitely in that club. Thank you so much! Please don’t hesitate to reach out if you have questions. I’m happy to help.

Dr. Mikel Delgado [1:01:31] Who can turn down that offer to get their question answered?! 

Monica DeBosscher [1:01:38] Thank you so much, Dr. Carl! Thanks everyone, again, for joining us. Just a reminder to keep a lookout for an email from Good Dog. It’ll have the recording of today’s webinar. If you aren’t yet a member of our community, we’d love to have you join us, so please visit www.gooddog.com/join so you can stay up to date on all of our future webinars like this one!