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View Full Version : Penderis interview: EFS gene test coming in spring!



Karlin
4th February 2011, 10:58 PM
I enjoyed meeting neurologist Prof. Jacques Penderis today at the annual Irish veterinary conference in Dublin. Prof Penderis is based at the University of Glasgow and is the leading researcher into episodic falling syndrome (EFS), a neurological condition known only in Cavaliers. He very generously gave me about an hour of his time in advance of giving three different presentations spanning the afternoon of the first day of the conference. I also had permission to return and attend his final presentation on neurological conditions in Cavaliers, which was really interesting.

I am going to write all of this up in more detail, probably tomorrow, but I wanted to flag one of the very exciting highlights, which is the fact that his team will be producing a genetic test for episodic falling to be released within the coming months, probably around April. This was developed in partnership with the animal health trust (AHT) in the UK. This is a very exciting development! His research team announced it had pinpointed the gene responsible for EFS last November. It turns out the condition is caused by a simple recessive trait, which makes it much easier to exactly locate and also easier to address, as well as easier to create a genetic test. Basically, breeders will be able to test to see whether any dog carries the gene for EFS. By eliminating dogs with the gene–or at least initially breeding dogs with the gene to dogs without the gene iF a wider gene pool is needed, as is probably the case as he describes this as a 'widespread' condition, both internationally and within the breed generally–gradually the incidence will drop in the condition could be entirely eradicated.

He said the gene involves the brain, and this is definitely not a muscular disorder (he said one paper was published that erroneously stated this a while back, but it is clear this is not the case). he said the gene is a quite interesting one, and that it has not in the past been known to be involved with genetic conditions, and the discovery may be of help in human medicine. But he could not give me any detail because the results are not yet published.

He also noted that he would define episodic falling as a *common*, not a rare condition in the breed. He said the incidence of EFS would be much higher than of epilepsy, for example–he would consider cavaliers to be “moderately” affected by epilepsy. He also said the vast majority of cases are very mild, with many stabilizing by age 1. He said it is actually quite rare for cases to be severe or to require a dog to be euthanized.

We split the hour pretty much evenly between EFS and SM. Some of the key points that I found interesting during our discussion on SM was his observation that they see almost no other breed than cavaliers coming in with SM, and he thinks it is actually quite rare in other breeds, including the toy breeds/brachycephalic dogs. He says they do not even see it as an occasional incidental finding when doing MRIs on other breeds, whereas they would commonly find CM and often SM on any cavalier MRI. He said he is not sure why one center in the US has seen up to 40% of its SM caseload in other breeds, and wonders if this is due to a local problem in certain US populations of breeds. he noted yorkies are one breed they see with SM as well.

He also would be quite conservative on choosing whether to do surgery– he feels surgery is something to consider after medication fails, or in young severely affected dogs. He said he did not feel there was any outstanding evidence so far that surgery is a better choice than medications and notes existing studies are more about anecdotal evidence on whatever approach a given team is doing. (This is true–there has been no proper comparative study.) He also noted, however, that perhaps there were benefits to doing surgery when affected dogs were young, before their syrinxes have a chance to expand and cause damage.

He is quite convinced that the problem of SM and many of these other neurological issues lies in the shape of the cavalier skull; he said some "extreme" internal feature not yet identified that has been bred in which now sometimes causes serious problems inside the brain and the spine as a result, amd a high degree of CM/SM ( though he uses the terms Chiari malformation and syringohydromyelia himself). He emphasized (as have other researchers) that this has nothing to do with any obvious outward shape of an individual skull or head but has to do with the fact that the dog is generally in the brachycephalic category and that there is some *internal* element affected by this particular type of skull in this particular breed. he noted that there are neurological conditions known throughout the brachycephalic breeds.

He encouraged breeders to continue to scan and submit scans and DNA As the only way forward for addressing SM, which he described as a more serious and difficult problem than EFS. He said that it may be in future that the Cavalier will be pointed to as one of the healthier breeds because with breeder support, some of its genetic problems will have been identified and breeders will have the tools to breed away from these neurological issues.

He also noted that he felt it was beneficial that different researchers approach these health issues from different directions and with different ideas, including treatment ideas, because this is more beneficial in trying to understand and resolve the problem. in that sense, he indicated it would be quite counterproductive for every researcher to have a common agreement around these health issues. The fact that many people have had many ideas has helped already to eliminate some ideas and hone in on others.

Anyway those are some highlights. I attended his one hour presentation and took quite a few notes. He went through a number of neurological conditions that he said feature more predominantly in the breed than in many other breeds. when I get a chance to write up the presentation I will note all of those.

Margaret C
4th February 2011, 11:33 PM
A really interesting interview. Thank you Karlin.

Nicki
5th February 2011, 11:26 AM
That is absolutely fantastic news Karlin about EFS!!! b*n*n*b*n*n*b*n*n*


I'm so thrilled, it sounds really hopeful that it will be "easy" to breed away from it, as long as genetic tests are carried out. I do hope that the Cavalier clubs will be proactive with this and hopefully arrange testing - I'm not sure what would be required - I suspect that it may just need the mouth swabs? so it could be done at the championship shows?

Anyway I'm getting ahead of things here, just SO excited about it!!


It's really good that his research may also help people - this has happened with SM too 8-)


It's sad that he thinks SM is such a common problem in Cavaliers - although we've had many other issues, we have been very fortunate to avoid this particular one so far, although many of our dogs have not come to us until after 1 year of age.


It was really kind of him to give you an whole hour - that's a long time for someone who is incredibly busy and must have a lot of requests for his time and shows that he holds you in high respect.


He also noted that he felt it was beneficial that different researchers approach these health issues from different directions and with different ideas

I really admire him for this comment - and it is so true - I know there have been ideas put forward which have been found to be incorrect, but this is how we learn and move forward.


I look forward to reading the full notes - no pressure Karlin :lol:

Bet
5th February 2011, 01:54 PM
That is absolutely fantastic news Karlin about EFS!!! b*n*n*b*n*n*b*n*n*


I'm so thrilled, it sounds really hopeful that it will be "easy" to breed away from it, as long as genetic tests are carried out. I do hope that the Cavalier clubs will be proactive with this and hopefully arrange testing - I'm not sure what would be required - I suspect that it may just need the mouth swabs? so it could be done at the championship shows?

Anyway I'm getting ahead of things here, just SO excited about it!!


It's really good that his research may also help people - this has happened with SM too 8-)


It's sad that he thinks SM is such a common problem in Cavaliers - although we've had many other issues, we have been very fortunate to avoid this particular one so far, although many of our dogs have not come to us until after 1 year of age.


It was really kind of him to give you an whole hour - that's a long time for someone who is incredibly busy and must have a lot of requests for his time and shows that he holds you in high respect.


He also noted that he felt it was beneficial that different researchers approach these health issues from different directions and with different ideas

I really admire him for this comment - and it is so true - I know there have been ideas put forward which have been found to be incorrect, but this is how we learn and move forward.


I look forward to reading the full notes - no pressure Karlin :lol:

PENDERIS INTERVIEW : EFS GENE TEST COMING IN SPRING

Can I also join in to Thank Karlin for all the Information she has Posted.

This Gene Information should now give the Impetous for any-one wanting to buy a Cavalier ,only buy from a Cavalier Breeder who is prepared to give Publicly for all to see , that they are Health Testing their Cavaliers ,and following the Breeding Guidelines for SM and MVD, and not hiding behide the Well Used Phrase of some Cavalier Breeders, I only use this Information for MY Benefit .

Why are those Cavalier Breeders so Scared to come out in the Open and say what the Health Results are for their Cavalier Breeding Stock?

Bet

Nicki
5th February 2011, 04:08 PM
Barbara Reese asked me to post the following:

I am absolutely ecstatic about this, as you can probably guess. I knew this was happening but couldn't say as they wanted to publish first . Do admit to feeling a bit vindicated after all the years I have spent being told to keep my mouth shut because of the complete denial in the breed.

EF is a lot more prevalent than anyone thinks. A great many of them are so mildly affected that their owners probably wouldn't notice and most of the more severe cases are/have been misdiagnosed as epilepsy. It is in every line just the same as SM but some lines (particularly wholecolours) are worse than others. Being a single recessive it can lie dormant for many generations and then hit out of the blue. Over the last ten years there have been more and more carriers and more affected dogs reported. Hardly a week goes by that I don't have someone contact me for help and I am seriously not exaggerating.:(

There are many movement disorders and though Scottie Cramp is very similar , as far as I am aware, it is not exactly the same.

The very interesting thing about this gene is that it has been found to be connected to the brain. It has long been thought that EF was a muscular condition but this has been found to not be the case. I have long thought that EF and SM may be connected in some way ( though the experts don't agree with me). There are so many similar symptoms and I have quite a lot of dogs reported that are definitely showing symptoms of both. I just wonder how a breed with such a small genepool can sustain two neurological diseases over such a long period of time. Maybe this gene could help with SM, who knows.

The important part now is for breeders to use this test and identify carriers, even if you have never seen a case in your own lines you may be very surprised at what you find.

Grateful thanks must go to everybody who has contributed to this research and made this possible but especially to Christa Krey in New Zealand who never gave up and through her test mating program proved that this was hereditary and was also a recessive gene.
Barbara

Nicki
5th February 2011, 04:18 PM
Barbara has worked incredibly hard and has been campaigning for this research for 30 years!! :thnku::thnku::thnku:

It is a tribute to her that we are now in this wonderful position where there is the opportunity to rid the breed of one of the horrible conditions which causes so much distress both to our beloved companions and their guardians.

Wagtails
5th February 2011, 04:19 PM
Thanks for posting Barbara's response, Nicki. She was SOooo helpful to me when my Megan was first diagnosed with SM (I mistakenly thought it might be EFS at first and contacted her via her excellent website).

Hoping to get to South Wales soon, Barbara, so will make contact when I know when :thmbsup:

molly
5th February 2011, 09:13 PM
Thanks so much for this exciting news! I have an EFS girl and this is very welcome info for any effected cavalier and for future breeding.

sarahangel
5th February 2011, 09:22 PM
Thank you so much for this excellent information . I have one dog here that I believe has a very mild form of EFS only bought on by extreme icey conditons underfoot. If we can use a dna test, we may not have to exclude all carriers from breeding and further reduce the gene pool.

RodRussell
5th February 2011, 10:35 PM
This is terrific news. Also surprising about its commonality and the early resolution for most cases.

Karlin, did Dr. Penderis discuss these findings in his talk at VICAS conference?

Dr. Penderis, Barbara Reese, Dorothie Hellman, Chrsita Krey, and Tina Whittaker have kept this issue alive for the past several years. They deserve great credit for this discovery.

This recent discovery of EFS as being associated with the brain adds another piece to a weird possible puzzle. Could it be that SM, EFS, low blood platelets (thrombocytopenia), giant platelets (macrothrombocytopenia), and early-onset MVD all could be linked in the CKCS? In 1997, Drs. Jens Häggström and Clarence Kvart of Sweden suggested in a 1997 article that thromboembolic events in the cerebral circulation of blood may be involved in EFS. In 2010, Dr. Mark Oyama suggested that there may be a link between cavaliers' giant platelets (carriers of serotonin -- the brain food for good naturedness) and the breed's high incidence of mitral valve disease. Now we have Barbara Reese suggesting a possible link between EFS and SM. Since Dr. Penderis' talk at the veterinary conference this weekend combined EFS and SM, I wonder if he thinks there may be a connection. It probably is far too early to even think about such a thing, but who would have thought that the brain food -- seratonin -- which gives cavaliers their marvelous temperament would be carried by giant blood platelets and planted on mitral valve flaps, thereby inducing the valve's deterioration?

sunshinekisses
6th February 2011, 01:37 AM
This is great news...a big thank you to all the dedicated people that won't give up on the cavalier breed. :D

Bet
6th February 2011, 10:34 AM
This is terrific news. Also surprising about its commonality and the early resolution for most cases.

Karlin, did Dr. Penderis discuss these findings in his talk at VICAS conference?

Dr. Penderis, Barbara Reese, Dorothie Hellman, Chrsita Krey, and Tina Whittaker have kept this issue alive for the past several years. They deserve great credit for this discovery.

This recent discovery of EFS as being associated with the brain adds another piece to a weird possible puzzle. Could it be that SM, EFS, low blood platelets (thrombocytopenia), giant platelets (macrothrombocytopenia), and early-onset MVD all could be linked in the CKCS? In 1997, Drs. Jens Häggström and Clarence Kvart of Sweden suggested in a 1997 article that thromboembolic events in the cerebral circulation of blood may be involved in EFS. In 2010, Dr. Mark Oyama suggested that there may be a link between cavaliers' giant platelets (carriers of serotonin -- the brain food for good naturedness) and the breed's high incidence of mitral valve disease. Now we have Barbara Reese suggesting a possible link between EFS and SM. Since Dr. Penderis' talk at the veterinary conference this weekend combined EFS and SM, I wonder if he thinks there may be a connection. It probably is far too early to even think about such a thing, but who would have thought that the brain food -- seratonin -- which gives cavaliers their marvelous temperament would be carried by giant blood platelets and planted on mitral valve flaps, thereby inducing the valve's deterioration?


PENDERIS INTERVIEW : EFS GENE TEST COMING IN SPRING!


Could I add another Thought.

When our Becky ,B/T developed Epilepsy ,I collected around 40 pedigrees of Cavaliers aslo suffering from Epilepsy , I 'd seen some Cavalier Pedigrees of Cavaliers with EFS , they were very Similar.

Could the EFS Gene be in the same Location maybe as where the Epilepsy Gene could be?

Also maybe now that the EFS Gene has been found, the Few Cavalier Breeder Vociferous Doubters about the Cavaliers' Health Problems of SM and MVD will have to Accept that the only way for our Cavalier Breed to Survive, is by finding the Genes for both those Two Conditions.

Bet

Karlin
6th February 2011, 12:23 PM
Hi Bet -- it definitely is not the same gene, and EFS is completely unrelated to epilepsy, according to Prof Penderis.

A genetic test for CM/SM is I think critical for the survival of the breed. I have heard experts describe the situation for the breed as being 'on the brink' now, because of how widespread SM and MVD now are -- both create so much suffering and are really unacceptable as a 'norm' for any animal. Without careful breeding based on careful testing and following protocols and full honesty about whether dogs are affected or not, I cannot see a very long future for cavaliers.

I am watching my own lovely Lucy in what are surely her final weeks or months now, with such a severe murmur on both sides of her heart that she shakes when at rest. She is still full of personality and otherwise in great form -- this is a dog that should easily live many more years IF we didn't have the hideous scourge of MVD in the breed. I have another with a grade 3 murmur by age 6, three with SM, two deaf or nearly deaf by middle age, three with PSOM. What kind of "normal" life is this for these dogs? :(

Bet
6th February 2011, 01:33 PM
Hi Bet -- it definitely is not the same gene, and EFS is completely unrelated to epilepsy, according to Prof Penderis.

A genetic test for CM/SM is I think critical for the survival of the breed. I have heard experts describe the situation for the breed as being 'on the brink' now, because of how widespread SM and MVD now are -- both create so much suffering and are really unacceptable as a 'norm' for any animal. Without careful breeding based on careful testing and following protocols and full honesty about whether dogs are affected or not, I cannot see a very long future for cavaliers.

I am watching my own lovely Lucy in what are surely her final weeks or months now, with such a severe murmur on both sides of her heart that she shakes when at rest. She is still full of personality and otherwise in great form -- this is a dog that should easily live many more years IF we didn't have the hideous scourge of MVD in the breed. I have another with a grade 3 murmur by age 6, three with SM, two deaf or nearly deaf by middle age, three with PSOM. What kind of "normal" life is this for these dogs? :(

Karlin,

Can I say I know what you are going through with Lucy.

For some Cavalier Breeders to be Claiming that they are Proud of Their Professionalism in how they have Bred Cavaliers , I really don't know what Planet they are living in.

How has the Breed reached the State it's in to-day, many of those so-called Breeders have a Lot to Answer for.
If that is what is called Professionalism ,I have another name for it.

As you mention the only way for the Breed to be Salvaged ,is for all those Cavalier Breeders who are on Committees ,stop trying to Influence the other Cavalier Breeders who are trying their Best to save our Cavaliers and let them move on with the Researchers to find the Genes for SM and MVD ,and at the Moment ,most importantly follow what the Researchers are telling them ,follow the Cavalier Breeding Protocols.

I just wonder when the Cavalier Pedigrees were so Similar for EFS and Epilepsy is this a Result of the In-Breeding that has been carried out within our Breed.

Bet

Margaret C
6th February 2011, 03:22 PM
Dr. Penderis, Barbara Reese, Dorothie Hellman, Chrsita Krey, and Tina Whittaker have kept this issue alive for the past several years. They deserve great credit for this discovery.



Congratulations and my sincerest thanks to them all.

Margaret C
6th February 2011, 03:48 PM
A genetic test for CM/SM is I think critical for the survival of the breed. I have heard experts describe the situation for the breed as being 'on the brink' now, because of how widespread SM and MVD now are -- both create so much suffering and are really unacceptable as a 'norm' for any animal. Without careful breeding based on careful testing and following protocols and full honesty about whether dogs are affected or not, I cannot see a very long future for cavaliers.



Unfortunately true, so how frustrating that influential breeders, with their "Apres moi le Deluge" mentality, are still trying to prevent publication of MRI results.

They do not care who gets hurt, dogs or owners, as long as there will be no way that anyone can prove they are breeding irresponsibly.

The sad thing is that there is an enormous demand for puppies from breeders that follow the health protocols. It would actually be good business sense to breed ethically.

emmastewartliberty
6th February 2011, 06:05 PM
Thank you for this Karlin. Basically Nikki summed up everything brilliantly that I wanted to say in her first reply to this thread.Plus just to say I'm so sad to hear that you and your little one are having tough times - thinking of you.

Desrae
6th February 2011, 09:48 PM
Oh wow, that really is great news, it gives hope for us, for our furry friends and the cavalier breed.