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Degenerative Myelopathy

Degenerative Myelopathy

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Test Overview:

Degenerative myelopathy is most commonly seen in the German Shepherd Dog, although other breeds are also predisposed, including the boxer, Cardigan and Pembroke Welsh Corgi, Siberian husky and the Rhodesian ridgeback. This disease is normally seen around middle age, and in general diagnosis can only be confirmed at post mortem examination. Breed surveys of some predisposed breeds indicate a fairly low occurrence rate, but most experts think this rate is actually much higher, due to the lack of post mortem follow up of the majority of suspected cases. Signs are due to the immune-mediated destruction of a part of the nerves in the spinal cord, leading to loss of these nerve fibres. The first sign is knuckling of the hind feet, and hind limb ataxia. Once the spinal cord damage progresses past this initial stage (termed proprioceptive deficits), the effectiveness (if any) of treatment is much diminished. Hence early diagnosis is vital. Following this initial stage, hind limb reflexes are affected, then weakness in the hind limbs develops, progressing to total paralysis. Once a dog shows these signs it will almost always respond poorly to therapy. Eventually destruction progresses from the middle of the spinal cord to the upper cord and brain stem, leading to forelimb weakness and eventually interference with the muscles of breathing, causing death. Most dogs are euthanased for humane reasons before this happens. Treatment is with specific supplements and drugs aimed at interfering with the immune destruction in the spinal cord, to slow further nerve damage. The effectiveness of this treatment is variable, but is only of benefit if started as early as possible. Once nerves are lost, they will not be replaced. Degenerative myelopathy cannot be cured. A DNA test is available for predisposed pure breeds to carry out screening of breeding animals.

Category:

Nervous system / Neurologic - Associated with the brain, spinal cord and nerves

Gene:

Superoxide dismutase 1 (SOD1) on chromosome 31

Variant Detected:

chr31:26540342 (canFam3): G>A

Severity:

Moderate. This disease can cause significant signs of discomfort and/or dysfunction in affected animals. It may involve relatively high treatment/management costs, and can sometimes reduce life expectancy.

Mode of Inheritance:

Autosomal Recessive with Incomplete Penetrance

Recommended Screening:

1. All breeding animals should have a DNA test prior to entering into a breeding program - eg at 1 year of age. 2. Neurologic examination of all animals at annual veterinary check-up from middle age (3-4 years) onwards. 3. Offer DNA testing to all owners of puppies if his parents have not been screened.

Research Citation(s):

Awano T, Johnson GS, Wade CM, Katz ML, Johnson GC, Taylor JF, Perloski M, Biagi T, Baranowska I, Long S, March PA, Olby NJ, Shelton GD, Khan S, O'Brien DP, Lindblad-Toh K, Coates JR. Genome-wide association analysis reveals a SOD1 mutation in canine degenerative myelopathy that resembles amyotrophic lateral sclerosis. Proc Natl Acad Sci U S A. 2009 Feb 24; 106(8):2794-9. [PubMed: 19188595] Coates JR, March PA, Oglesbee M, Ruaux CG, Olby NJ, Berghaus RD, O'Brien DP, Keating JH, Johnson GS, Williams DA. Clinical characterization of a familial degenerative myelopathy in Pembroke Welsh Corgi dogs. J Vet Intern Med. 2007 Nov-Dec; 21(6):1323-31. [PubMed: 18196743] Coates JR, Wininger FA. Canine degenerative myelopathy. Vet Clin North Am Small Anim Pract. 2010 Sep; 40(5):929-50. [PubMed: 20732599] Miller AD, Barber R, Porter BF, Peters RM, Kent M, Platt SR, Schatzberg SJ. Degenerative myelopathy in two Boxer dogs. Vet Pathol. 2009 Jul; 46(4):684-7. [PubMed: 19276068] Shaffer LG, Ramirez CJ, Sundin K, Carl C, Ballif BC (2015) Genetic screening and mutation identification in a rare canine breed, the Drentsche patrijshond. Vet Rec Case Rep. 3:e000185. Shaffer LG, Ramirez CJ, Sundin K, Connell LB, Ballif BC (2016) Genetic screening and mutation identification in a rare canine breed, the Cesky fousek. Vet Rec Case Rep. 4:e000346. Shelton GD, Johnson GC, O’Brien DP, Katz ML, Pesayco JP, Chang BJ, Mizisin AP, Coates JR. Degenerative myelopathy associated with a missense mutation in the superoxide dismutase 1 (SOD1) gene progresses to peripheral neuropathy in Pembroke Welsh Corgis and Boxers. J Neurol Sci. 2012 Jul 15;318(1-2):55-64. [PubMed: 22542607] Zeng R, Coates JR, Johnson GC, Hansen L, Awano T, Kolicheski A, Ivansson E, Perloski M, Lindblad-Toh K, O'Brien DP, Guo J, Katz ML, Johnson GS. Breed Distribution of SOD1 Alleles Previously Associated with Canine Degenerative Myelopathy. J Vet Intern Med. 2014 Feb 13. doi: 10.1111/jvim.12317. [PubMed: 24524809]

Associated Breed(s):

Alaskan Malamute, American Bulldog , American Bully , American Cocker Spaniel, American Eskimo Dog, American Hairless (Rat) Terrier, American Pit Bull Terrier, Australian Bulldog, Australian Cattle Dog, Australian Cobberdog, Australian Kelpie, Australian Labradoodle , Australian Shepherd, Australian Silky Terrier, Australian Terrier, Barbet, Beagle, Belgian Lakenois Shepherd, Belgian Malinois Shepherd, Belgian Tervueren Shepherd , Bernardoodle, Bernese Mountain Dog, Bichon Frise, Bloodhound, Boerboel, Border Collie, Borzoi, Boston Bulldog, Boxer , Boykin Spaniel, British Bulldog, Bullmastiff, Canaan Dog, Cane Corso Italiano, Cardigan Welsh Corgi, Catahoula, Cavador, Cavalier King Charles Spaniel, Cavoodle, Chesapeake Bay Retriever , Chinese Crested, Chow Chow, Collie Rough, Collie Smooth, Coton De Tulear, Curly Coated Retriever, Dutch Shepherd, English Springer Spaniel, English Toy Terrier, Finnish Lapphund, French Bulldog, German Pinscher, German Shepherd Dog, Glen of Imaal Terrier, Golden Retriever, Goldendoodle, Great Dane, Great Pyrenees, Groodle, Harlequin Pinscher, Irish Setter, Irish Wolfhound, Kerry Blue Terrier, King Charles Spaniel, Koolie , Labradoodle , Labradoodle Retrodoodle , Labrador Retriever, Landseer ECT, Maremma Sheepdog, Miniature Pinscher , Miniature Poodle, Mixed Breed, Moodle, Moyen Poodle, Norfolk Terrier , Norwich Terrier, Nova Scotia Duck Tolling Retriever , Old English Sheepdog , Patterdale Terrier, Pembroke Welsh Corgi, Pomeranian, Portuguese Water Dog, Pug, Puli, Rat Terrier, Rhodesian Ridgeback , Rottweiler , Saint Bernard , Scottish Terrier , Shetland Sheepdog, Shih tzu, Shortybull, Soft Coated Wheaten Terrier, Spoodle, Staffordshire Bull Terrier , Standard Poodle, Tenterfield Terrier , Tibetan Spaniel, Tibetan Terrier , Toy Poodle, Wallace Bulldog, Welsh Terrier , White Swiss Shepherd, Wire Fox Terrier,
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