Correcting the Confusion around Degenerative Myelopathy
Brenda Bonnett, BSc, DVM, PhD, Veterinary Science Officer, International Partnership for Dogs
Jerold Bell, DVM, Adjunct Professor of Genetics Department of Clinical Sciences Cummings School of Veterinary Medicine Tufts University, USA, Chairman, Hereditary Disease Committee, World Small Animal Veterinary Association (WSAVA), and IPFD friend and collaborator has written the definitive paper on Degenerative Myelopathy (DM), DEGENERATIVE MYELOPATHY-DIAGNOSIS AND INHERITANCE.
This information is needed and must be disseminated widely – to veterinarians, breeders, kennel and breed clubs, and owners to counteract many areas of misunderstanding and confusion about this diagnosis and about genetic testing for it. This paper brings together the evaluation of the best evidence, consultation with experts and researchers, and an understanding of the issues in both veterinary practice and the world of breeders. We encourage all to read and share this paper, to try to revise/reverse some of the problems that have arisen due to confusion and over-reaction about the condition and testing.
In a nutshell
These are the key excerpts from the paper [bold highlights and some additional comments from IPFD]:
“Degenerative myelopathy (DM) is a specific, infrequently encountered, fatal inherited disorder of slowly progressive spinal cord degeneration in dogs.” … “The biggest issue with DM is misdiagnosing it in a dog affected with another treatable or non-fatal disease.” … [Detailed information on clinical presentation, diagnosis, and treatment are available in the article .]
1. Occurrence: “It presents most commonly [although still not a ‘common’ condition] in German Shepherd Dogs and Boxers. It is sporadically seen in Pembroke Welsh Corgis, Cardigan Welsh Corgis, Bernese Mountain Dogs, Rhodesian Ridgebacks, Borzoi and Chesapeake Bay Retrievers. It is rarely diagnosed in other breeds or mixed-breed dogs.”
2. Genetic Testing:
a. “If a genetic test for the sod1 variant is not homozygous “at risk” this rules out DM as a differential. However, a homozygous “at risk” result is NOT diagnostic and should NOT be used to confirm a diagnosis of DM.”
b. “The high rate of sod1 DM genetic testing has put the term degenerative myelopathy into common conversation. This has caused great confusion” … “as well as damage to breed gene pools from inappropriate selection against the sod1 variant.“
c. “The mode of inheritance of DM has always been considered to be complex – involving more than one gene pair.” … “Canine DM is an animal model for human amyotrophic lateral sclerosis (ALS; Lou Gehrig’s disease). In ALS over 25 identified genetic mutations cause disease liability;” This means that although it is believed that “almost all” [but NOT all] dogs must have the sod1 gene in order to experience the condition, the sod1 gene is not enough on its own to cause disease, and, most importantly: “The frequency of the sod1 variant is over 20-90% in more than 30 breeds, although no dogs in most of these breeds have ever been confirmed with DM.”
“There are many disorders affecting the spinal cord that can be classified as degenerative (progressive) myelopathies (spinal cord diseases).” And even these are relatively rare conditions. If the sod1 gene was that important on its own, veterinarians would be “diagnosing hundreds of thousands of DM affected dogs every year, as opposed to the infrequent diagnoses that are observed”.
d. “It is obvious that even in breeds with pathological confirmation of clinical disease; the variant frequency is exponentially higher than the frequency of clinically affected dogs, and the homozygous state has low penetrance and is poorly predictive of clinical disease.” [See table in article] In simple terms - there will be many (mostly) false positives if the results of the sod1 test are believed to indicate DM.
Given the relative uncommonness of this disease, and its generally late onset, breeders must be cautious about prioritizing control of this condition over other diseases and health concerns which are more common, or important in all breeds. Yes, this is a devastating disease for dogs and owners, but it is not appropriate to implement breed-wide control measures like eliminating sod1 homozygous dogs from breeding. “The greatest issue with the misuse of sod1 genetic test results (both in breeds with and without confirmation of affected DM dogs) is where breeders are devastating their gene pool diversity by selecting against the sod1 variant.” Simply put: excessive use of this test will negatively impact the overall health and genetic diversity of the breed.
“While the sod1 variant is the most frequent DNA variant identified in dogs, clinical degenerative myelopathy needs to be put back in the RARE and INFREQUENTLY DIAGNOSED category where it belongs.” One of the reasons for this is that the test was made widely available and sometimes promoted by genetic testing services, in spite of its limited effectiveness or relevance for most breeds.
It will require a concerted effort by kennel and breed clubs to reverse the trends in ‘popularity’ of widespread use of genetic testing for sod1, and the focus on DM. But this effort must be made for the overall health and welfare of breeds. Genetic testing services are called upon to help improve messaging about this test. Veterinarians and genetic counsellors must also participate. The infographic referenced below may help. It is available for anyone to use/ translate, etc. Let us know if we can assist ( email@example.com ).
See the article: DEGENERATIVE MYELOPATHY-DIAGNOSIS AND INHERITANCE
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