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*Pauline*
17th February 2010, 12:21 PM
Muscular dystrophy in the Cavalier King Charles Spaniel. (http://www.rvc.ac.uk/Research/News/musculardystrophy.cfm)

A Duchenne Muscular Dystrophy Gene Hot Spot Mutation in Dystrophin-Deficient Cavalier King Charles Spaniels (http://www.plosone.org/article/info%3Adoi/10.1371/journal.pone.0008647).

Research News.

A Duchenne Muscular Dystrophy Gene Hot Spot Mutation in Dystrophin-Deficient Cavalier King Charles Spaniels is amenable to Exon 51 Skipping.

In new research published in PLoS ONE on 13th January 2010, veterinary scientists, including Dr Richard Piercy and Gemma Walmsley at the Comparative Neuromuscular Diseases Laboratory of the Royal Veterinary College, have characterized muscular dystrophy in the Cavalier King Charles Spaniel after an affected dog was referred to the Neurology and Neurosurgery Team at the Queen Mother Hospital for Animals.

Duchenne Muscular Dystrophy (DMD) is a painful, debilitating and fatal human genetic muscle disorder. The X-linked condition afflicts 1 in 3500 boys and results from inherited or spontaneous mutations in the dystrophin gene which encodes a structural muscle protein. The disease results in a progressive destruction of skeletal and heart muscles and affected boys are usually wheel-chair bound by their teens and death usually occurs in the twenties following respiratory or heart failure.

Dystrophinopathies are also the most common cause of muscular dystrophy in dogs and have a similarly severe phenotype to the analogous human condition. The precise genetic mutation has only been determined previously in a small number of breeds. Work performed at the Royal Veterinary College found that the underlying defect in Cavalier King Charles Spaniels is in the region of the dystrophin gene that is most commonly mutated in humans. Also, in collaboration with researchers at University College London and the University of California San Diego, we have characterized the disease in three dogs and demonstrated the feasibility of a therapeutic approach that is predicted to ameliorate the severity of disease in many human patients with DMD.

This research complements ongoing human clinical trials into genetic therapies for muscular dystrophy and has the potential to help dogs and boys afflicted with this devastating disorder.

Dr Richard Piercy is a Senior Lecturer in Equine Medicine and Neurology at the Royal Veterinary College. Gemma Walmsley is a PhD student working in the Comparative Neuromuscular Diseases Laboratory.

Tania
17th February 2010, 02:17 PM
Great article Pauline! I also found this. http://www.plosone.org/article/info:doi/10.1371/journal.pone.0008647

Can someone translate please!

Nicki
17th February 2010, 08:37 PM
There was some information about this posted last Summer by Karlin, obviously in advance of the full research being published

http://www.cavaliertalk.com/forums/showthread.php?31060-New-genetic-mutation-identified-muscular-dystrophy-in-CKCS&highlight=Muscular+Dystrophy

Tania
17th February 2010, 08:43 PM
Thank you Nicki that is a great help.

Eva
6th July 2011, 10:33 PM
A few months my sweet little CKCS puppy, Clinton, passed away from this disease, which is closely related to the Duchenne Muscular Dystrophy that affects humans. When I was trying to find out information, this thread was one of the first items that popped up in my search. Thank you ladies for posting the links to the research article - it was immensely helpful to me as I was struggling to gain an understanding of this disease.

Clinton was only 10 1/2 months when he passed away. He had always been quieter and a little slower to develop than his sister, who was his littermate, but we started seeing unusual symptoms when he was about four months old. It began as a reluctance to sit after walks, which developed into cries of pain and eventually a reluctance to even go for walks at all. We, my husband and I, went through a barrage of testing in an attempt to diagnose his issues. The initial diagnosis was panosteitis, which is a form of puppy growing pains that dogs eventually grow out of. Later testing revealed sky high liver levels, particularly his CK levels. After ruling out liver disease and spinal issues (he had an MRI), we thought we had arrived at a diagnosis: immune mediated myositis. Clinton passed away three days after we received that diagnosis. It was shocking, unexplainable and heartbreaking. Despite his issues, he was still a happy little puppy who liked to play with his sister and cuddle with us and did not look outwardly ill.

A necropsy was performed, and it stated that Clinton had Duchenne Muscular Dystrophy. The disease is so rare that it’s not even mentioned in veterinary textbooks according to one of our vets. As I mentioned before, I started to do a ton of internet research to get a handle on it. I had Clinton’s sister tested through the Royal Veterinary College to see if she was a carrier of the disease, which is caused by a gene mutation. The breeder had his mother tested. I just received the results a few days ago, and both dogs are carriers. I was waiting to write this post until I received confirmation of those results. My dog is spayed and the breeder is not going to breed her female again. Clinton and his sister were actually from her dog’s first litter. He was the only male. Without a long winded explanation of the genetics, females carry the disease while males are the ones who die from it. There are such things as manifesting carriers: females who exhibit mild symptoms of the disease.

As I said, Clinton’s symptoms began very early. If you have a puppy who is exhibiting signs of poor mobility or pain after exercise, I urge you to discuss muscular dystrophy as a possible diagnosis with your vet. Apparently some of the symptoms can include dysphagia (difficulty in swallowing) and macroglossia (enlarged tongue). Clinton had mild symptoms of dysphagia, particularly when drinking water. While not always associated with muscular dystrophy, extremely high CK levels are a big warning sign. Dr. Diane Shelton, one of the contributing authors of the CKCS study and one of the leading experts in the field of neuromuscular diseases published this article - Why the serum creatine kinase (CK) activity should not be ignored! (http://vetneuromuscular.ucsd.edu/cases/2010/Aug2010.html) - explaining her thoughts on the subject.

One of the U.S. researchers involved in the study told one of my vets that there is a “pocket” of this disease in CKCS in Santa Rosa. She also said that the disease is more prevalent than we think. I urge anyone who has experienced this disease or who has knowledge of it to share their insight. That way we can help build knowledge and exposure and hopefully get a better idea of just how prevalent it is among CKCS.

***UPDATE***
I spoke with a researcher who studies the disease in Golden Retrievers, and he said that Clinton's death at 10 1/2 months was unusual. Based on his experience with Golden Retrievers, dogs with the disease can often live to middle age and some even longer than that. As with humans with the disease, it progresses differently from individual to individual. Also, he said the biggest concern for female carriers is heart disease. He recommended that I have an EKG done for my female puppy who is a carrier, ideally one that would measure her heart rhythms for a few hours to detect arrhythmias.

mommytoClaire
7th July 2011, 12:51 AM
Oh, I am so sorry to hear about Clinton. Another gosh darn disease to worry about with our beloved Cavaliers. I am so sad.

Eva
7th July 2011, 10:12 PM
Thanks Cindy. I know, just another thing to worry about. I'm going to do my best to spread the word about the disease here in the states. I hope as awareness grows, so will accurate diagnosing of the disease.

Desrae
8th July 2011, 12:32 AM
Thank you Pauline for posting this!
Eva, I'm so sorry about you losing Clinton. It is good news that his breeder has stopped breeding from his parents, a very responsible breeder!
And Cindy, you're right about that, another disease to worry about.

Eva
18th August 2011, 06:11 PM
After Clinton passed away, I was searching for a way to get his sister and mother tested for the mutation. I contacted Vetnostic Laboratories, which has a test for the Golden Retriever version of this disease. They did not have a test, but committed to creating one. The test has now been created and they need samples to validate it. Please read below:

‘VetNostic Laboratories is currently looking for approximately 50 Cavalier King Charles Spaniel DNA samples to validate our CKCS-MD test. Collection is performed using a cheek swab kit which consists of three swabs per dog. A self addressed, postage paid, return envelope will be provided. Once we receive the swabs it will take approximately one week to obtain the results. Testing is free and result certificates will be provided.

The test is based on the mutation discovered by Walmsley et al.

To obtain a collection kit along with instructions, please email Rob Mason rmason@mdlab.com or call 877-255-9208’

Karlin
18th August 2011, 07:32 PM
Good for you for encouraging this! I will pass the info along. It would be good to let the ACKCSC and CKCSC know about this too.

RodRussell
18th August 2011, 08:01 PM
Good for you for encouraging this! I will pass the info along. It would be good to let the ACKCSC and CKCSC know about this too.

Yes, I guess it's time to add another page to the cavalierhealth.org website, too.

RodRussell
19th August 2011, 02:55 AM
Yes, I guess it's time to add another page to the cavalierhealth.org website, too.

What do you know? I found it! http://cavalierhealth.org/muscular_dystrophy.htm

Karlin
19th August 2011, 12:47 PM
:lol: I find that happens to me a lot too–I forget that I've already added things in!

Cathy T
19th August 2011, 04:31 PM
I've requested the swab kit and will be submitting Shelby's DNA. Hope it helps research.

anniemac
25th August 2011, 04:08 PM
I was a little late sending the email but heard back from Rob Mason. He said they have received 50 but would accept one more in an effort to identify as many carriers as they can.

*He told me only females can be carriers
*Males can be affected by MD but symptoms usually appear before age 1.

Since Elton is 4 and is not a female, he is not of use. He said if I had a female he would be happy to send a kit.

I am so sorry to hear about Clinton but thankful for what you have done to hopefully help cavaliers in the future :l*v: