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Positive Homozygous for PDK4/DCM1

6K views 18 replies 10 participants last post by  Q734 
#1 ·
Well, sh*t. Finally sent off the swabs for the DCM1 and DCM2 test at NCSU. Silas is positive homozygous (both genes affected) for PDK4 and, thankfully, negative for DCM2. According to the results, about 40 percent of dogs who are positive for DCM1 will develop DCM -- not quite as high as the percent of dogs who develop DCM if they test positive for DCM2 or anywhere near as high as dogs who test positive for both.

I know it doesn't really mean anything. It's not a death sentence; it just means I'll have to be more vigilant in his testing/monitoring. I'd almost rather NOT know this, tbh. Now it's just going to be this dark cloud hanging over us, this worry I'll have forever. Not that DCM wasn't ALWAYS a worry. But now I'll just be waiting for the train to hit.

UGH.
 
#2 ·
Honestly this is just information to have on hand. All Doberman owners need to do echoes and holters regularly, regardless of the results of this gene test. If you had gotten a negative/ negative you may have a false sense of security.

We all need to test at least yearly and try to catch the disease early, no matter where our dogs came from.
 
#3 · (Edited)
Now I’m confused. You say your dog has a 40% chance of developing DCM--which is less than the number quoted for all dobes.

Does the number of 40% mean 40% more likely than dogs without a homozygous PDK4? Or does the 58% number quoted below include dobes who are both occult and overt DCM (dogs tested who showed subclinical signs of arrhythmias plus dogs diagnosed with DCM?) while the 40% number means dogs that will develop clinical DCM?

According to studies done (see below), the incidence of DCM is closer to 50-60 %, which are more or less the numbers I have heard.


From two different sources: (Journal of Veterinary Medicine, and The Universities Federation for Animal Welfare UK)

Prevalence of Dilated Cardiomyopathy in Doberman Pinschers in Various Age Groups - Wess - 2010 - Journal of Veterinary Internal Medicine - Wiley Online Library

"DCM prevalence in various age groups was as follows: age group 1 (1 to <2 years) 3.3%, age group 2 (2 to <4 years) 9.9%, age group 3 (4 to <6 years) 12.5%, age group 4 (6 to <8 years) 43.6%, and age group 5 (>8 years) 44.1%. The cumulative prevalence of Doberman Pinscher cardiomyopathy was 58.2%. There was an equal sex distribution, but male dogs showed earlier echocardiographic changes than did female dogs, which had significantly more VPCs."


https://www.ufaw.org.uk/dogs/doberman-pinscher-dilated-cardiomyopathy

"It has recently been found that the overall prevalence of dilated cardiomyopathy in Dobermans in Europe is greater than 50%”.

 
#4 ·
From NCSU:

* Negative Result for both DCM1 and DCM2:The absence of both mutations in a Doberman indicates that the risk of developing DCM is low. It is still possible for a dog to develop heart disease. However, a negative result for both DCM1 and DCM2 indicates that a dog does not have either mutation known to cause DCM.

* Positive result for NCSU DCM1 only: About 40% of dogs with this mutation will develop DCM. Dogs that are positive for only DCM1 will not necessarily develop significant heart disease. Breeding recommendations: Dogs positive for DCM1 should NEVER be bred to a dog that is positive for NCSU DCM 2 since this will lead to dogs that are highest risk of developing DCM. Dogs that are positive homozygous for DCM1 should ideally not be bred.

* Positive Result for NCSU DCM2 only: About 50% of dogs with this mutation will develop DCM. Dogs that are positive for only DCM2 will not necessarily develop significant heart disease. Breeding recommendations: Dogs are positive for DCM2 should NEVER be bred to a dog that is positive for NCSU DCM1 (PDK4) since this will lead to dogs that are highest risk of developing DCM. Dogs that are positive homozygous for DCM2 should ideally not be bred.

* Positive result for both NCSU DCM1 and NCSU DCM2: Dogs that positive for BOTH DCM1 & DCM2 are at a very HIGH risk of developing DCM and should be carefully monitored by your veterinarian for signs of disease. Annual evaluation by a cardiologist with an echocardiogram and Holter monitor after 3 years of age is recommended. Breeding recommendations: Dogs that are positive for both DCM1 & DCM2 are at the HIGHEST risk of developing DCM and should ideally not be bred since they can pass both traits on. They should never be bred to a dog that is positive for either test.
 
#5 · (Edited)
So, NCSU is testing for two genes: DCM1/PDK4 and DCM2. Dogs who only have the DCM1 gene (like Silas) have a 40 percent chance of developing DCM. Dogs who have the DCM2 gene have a 50% chance of developing the disease. Dogs who have BOTH genes have a much higher chance of developing DCM. And dogs who have neither marker have a very low chance of developing DCM (but the fact that those dogs could still develop DCM means there are probably other, still unidentified genes that can cause DCM). So you have dogs with a very low chance of developing the disease and dogs with a very high chance of developing the disease, and everything in between, based on which of these two genes the dog has.

That 58% number, which I've also seen before, is an average of all Dobes. It doesn't look at whether those dogs have the DCM1 or the DCM2 gene, or both, or neither. This NCSU test breaks down the percentages into categories (DCM1 present, DCM2 present, both present, neither present). The other studies are an average of all those categories. So it may be true that 58% of all Dobes will develop DCM, but only 40 percent of Dobes with the DCM1 gene will develop DCM. Both figures can be true.

I think one other thing to note is that, if I remember correctly, those 50+ numbers were studies of European Dobes. I think it's been suggested by some studies that frequency may be higher in European Dobes.

And, remember too, a dog can have the genes that cause DCM but, for whatever reason, those genes don't get "switched on." Which is why some dogs can have both genes and still never develop DCM. And we don't know what switches those genes on or keeps them turned off. We just know a dog with both genes is much more likely to develop DCM.
 
#6 ·
I personally question the percentages because I have had person experience with 4 dogs - 3 are prior to any testing for PDK4 or the new "DCM2" - First bitch dropped dead at 7 1/2 - necropsy showed a viral infection around the lining of her heart which caused a rupture. 2nd dog 2 years old dropped dead at a dog show while on the grooming table - necropsy showed aneurysm of the brain. 3rd dog died at 5 - had been outside for a run came in jumped up on the couch laid down the then jumped straight up in the air and screamed - necropsy showed a lesion in the lung. Last was PDK4 negative holter good 6 months prior dropped dead at 7 1/2 necropsy showed cardio failure. So one out of 4 does make me question the percentages of actual cardio.

When Dr. Meurs announced the new DCM2 test she said dogs could be negative for both and still die of cardio yet she felt they had found all the mutant genes - I think we have to remember that 3 things cause or contribute to cardio - genetics, viral or bacterial and environmental stressors. There are no guarantees and we have seen plenty of examples of dogs that test **** live past 10. My question is does it mean that the ones that live past 10 have far more valuable strong heart genes that override the negative and should we eliminate those genes. How do we balance that and make sense of it all??
 
#8 ·
I strongly question those percentages, as I don't think we've come close to identifying all the gene mutations responsible for the development of DCM. I'm frankly surprised they are giving predictions about the development of the disease, as the last I'd heard they were strongly cautioning that these were only *one* component of many in a very complex disease. In humans, more than 50 gene mutations have been identified as linked to the development of DCM, so I hardly think that the identification of 2 mutations is predictive, at this point, of any kind of statistical probability of disease development.
 
#10 ·
Never regret Silaspup. It stinks your boy got a double dose of this gene, but what you're reading here is some healthy skepticism of the actual role the genes play in predicting DCM in a particular dog. In a study in Germany, they found the PDK4 gene to be of no value at all in predicting DCM in the European cohort of the breed, and in fact found the same mutation in something like 84 different breeds, majority of which don't have DCM as an issue.

So, I guess what it points out is how little we, or even the scientists studying the disease really know as cold hard facts. There are ongoing studies here and in Europe, so with ANY luck at all, some of these dedicated researchers will find some hard evidence of contributory genes to the problem. Meanwhile, with your guy, you just need to do what you would do anyway, test him annually or more often, if he were mine, I'd probably also do the blood tests for cardiac enzymes, these seem to be a very early indicator of something going wrong and then proper follow up can be done. They're also not as expensive to do, and the dog doesn't have to wear a vest for 24 hours<G>

Meanwhile love your dog, he doesn't know that there's anything potentially wrong, and lives life to the fullest every day. Enjoy that life journey with him, hopefully for many many healthy years!!
 
#11 ·
Why does it "stink"?
I happen to know a handful of dogs that their breeders/owners have publicly stated are homozygous for BOTH pdk4 and DCM2 genes. And guess what? All are well over 10 years of age. One just celebrated his 13th birthday and was showing in veterans.

What has been most disappointing about both of these tests is that it focuses on two genes out of a possible 50+ genes. There's no telling how many and in what combinations will produce cardio. For now, its best to just accept that the benefit of these tests is solely to promote additional research.
 
#12 ·
To be perfectly honest, I wouldn't lose any sleep over your results.

Dr. Muers' study seems primarily geared to sell diagnostic testing kits, like so many things veterinary researchers do. I have yet to see any meaningful follow-up, what is being done with the substantially larger sample size which has opened-up since the PDK4 "DCM" test has been commercially available? It's not like it was a slam-dunk, 100% conclusive genetic test, follow-up is definitely warranted to continuously validate the original conclusions. Failure to follow-up is bad science.

I still haven't seen any peer-reviewed papers published in support of the newer DCM2 test. Dr. Muers claims in that video that the dogs who test positive are at SUCH HIGH RISK THEY SHOULD NOT BE BRED!!!1!one!! Nothing in that video, which is the only information provided regarding the implications of the test, has actual data or rationale supporting that conclusion. What it is looking at? What was the sample size? This reeks of bad science.

I'm getting rather irritated at Muers and NCSU. If they're going to be making such strongly-worded recommendations, it's irresponsible and unethical for them to fail to put the rationale for such statements out there, such that folks are able to make educated decisions. They've had plenty of time to publish, and ideally would've done so before offering testing kits publicly.

I'm a huge fan of genetic diagnostic research and testing, but it's worthless garbage if misunderstood and misapplied.
 
#13 · (Edited)
To add to kalorics points, no one can validate the results for DCM2 as the location of the gene wasn't released. So Wess et al in Germany can't check the European population, nor can any of the labs working on health and longevity research for any breed validate the findings. I don't want to DISMISS it out of hand, but then again, it's really hard to jump on board when no one knows what it is they're testing, was it a sample of 50 dogs? 75? or was it closer to 100? No one knows. And the smaller the sample size, quite often the more skewed the results can be. After talking to some geneticists, their magic number seems to be one thousand for validating a finding. With that in mind, I'd love to see some follow up on the tested population of dogs. I'd also really like to see these labs use testing protocol that validates the breed before issuing results. The technology is out there, and it would take some of the dishonest submissions out of the equation(oh the stories you hear LOL!!)I truly hate seeing owners like Silaspup put through all the stress and worry, when it might be for naught
 
#14 ·
I have no faith in these markers, from this source.
And unless I'm given a compelling reason otherwise as of this writing refuse to do those tests on my guy out of protest and in honor of a friend who had to watch her PDK4 neg girl die in front of her TWICE. People are using these results as selling points for puppies and making breeding decisions on them when in fact these tests as they are *now* in the hands of the wrong people, could well be doing damage to the breed.
Just no.
Silas I would not sweat these gene markers.
 
#15 ·
Why does it "stink"?

Because the results, whether they're actually causative or not, cause a great deal of worry and stress in the owner of the dog. All of us can say a lot of things, don't worry, the research is still lacking etc, but it doesn't change how the owner feels one whit. A homozygous test result still strikes fear into the owners heart. So yeah, it stinks:frown3:
 
#16 ·
Thanks to those of you who offered empathy and, especially, to those of you who offered your reasons for distrusting the test. It's hard for me to piece things together when I hear owners saying they don't put stock in the test, but don't list reasons, and then I've got my cardiologist telling me it's a pretty darn good test. (Maybe he has access to information the rest of us don't. Or maybe he doesn't.)
 
#19 ·
Your dog's cardiologist said these gene tests were "pretty darn good"? :2surprise:

sigh.... You know I'm beginning to think more & more cardiology is an art form. I personally had a heart attack going on 2 years ago, no damage thankfully I was dehydrated & didn't know it but it was scary as hell. Woke up feeling great (can't say that very often) , thought I'd mow the yard on a gorgeous day, then felt like crap the rest of the day. (thought I'd somehow heatstroked myself altho it was only 70's outside)

One thing I was told in follow up is that tropinon levels can be elevated for a number of reasons besides heart damage: stress & infection can also raise levels. Oh & my electrolytes were off. It is frighteningly easy to become dehydrated.

So follow up appts where say I had an incident of "lightning" in my chest I'm told things like "well your ekg is good it's not your heart". No one but my gp seems to be able to offer any sort of explanation how I had a HA with only 40% blockage in 2 arteries other than "you must have had a spasm for just long enough".

Anyway I'm on my 2nd cardiologist and just tired of never getting solid answers for anything so I've become suspicious of that field. Seems unless something is GLARINGLY APPARENT RIGHT THEN AND THERE they can't give explanations or any solution.

So I concur w/the above that echos & holters and pedigree history carry more weight than these new "markers". I will never ever buy a dog based on these dcm gene tests until they start making sense with outcomes.
Real damage is being done RIGHT NOW w/these tests IMO.
 
#17 ·
Reasons?
I know of more than a few dogs that have tested negative for both genes and either succumbed to DCM or are currently living with CHF.

There is no science on earth that can explain that OTHER than there are simply more than two genes that cause DCM. And because of that it's hard to put much faith in a test that can't really tell me anything other than dogs who test negative MAY get DCM and dogs who test pos het MAY get DCM and dogs who test pos **** MAY get DCM.

Unfortunately for us, these tests are not as black and white as, say, a vwd DNA test. Where there can only be the 3 possibilities: clear, carrier, affected. I put more stock in Holter/echo and NTproBNP than I do in DCM1/DCM2 testing at this time.
 
#18 ·
We feel your pain. We have just lost our Leila to DCM. be thankful you did the test, and be diligent with your echo's and holters. Get yourself a good cardiologist and when the time comes, get Silas on meds. Hopefully all will turn out well. Leila showed nothing until it was far to late.
Our thoughts and prayers are with you and Silas.
 
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