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Veterinarian Technician July 2013 (Vol 34, No 7)

Degenerative Myelopathy in Pedigreed Dogs

by Jessica Erace, LVT

    The Pembroke Welsh corgi is one of several breeds that the American Kennel Club and the Orthopedic Foundation for Animals recommend testing for degenerative myelopathy.

    Many genetic tests are available for dogs and cats in the United States. Most of the tests are for dogs and were largely developed to facilitate inherited disease screening for breeders. Some tests are of interest to companion animal practitioners as a means of diagnosing otherwise occult disease or to rule out (or in) certain diseases. This article focuses on the DNA test for canine degenerative myelopathy.

    The Condition

    Degenerative myelopathy (DM; previously known as chronic degenerative radiculomyopathy) is a fatal, progressive spinal-cord disease affecting middle-aged and older dogs. Histopathic findings include noninflammatory degeneration of the white matter of the spinal cord, often beginning in the thoracic spine. The onset is usually at 7 years of age or older. Early DM is often described as having an insidious onset, as the first clinical signs include nonpainful weakness in the hind end and mild ataxia, making it easy to attribute to age-related orthopedic disease. Proprioceptive deficits soon appear, however, helping to distinguish DM from some other age-related orthopedic diseases.

    Dogs with DM develop increasing weakness that progresses to flaccid tetraparesis within 3 years. For some dogs, the progression is much faster; dogs are often euthanized for humane reasons within a year of diagnosis.1 There is no known treatment for DM, and no treatments given to delay the disease and ameliorate clinical signs have shown widespread success. Affected dogs remain mentally normal while becoming increasingly physically disabled. Though DM is not physically painful, it is a heartbreaking disease that can take a great emotional toll on the caretakers of affected dogs.

    The Genetics

    DM is best known as a disease of Welsh corgis and German shepherds. The strong breed association with DM facilitated genetic research. In 2009, researchers at the veterinary school at the University of Missouri discovered a mutation in the superoxide dismutase-1 (SOD1) gene associated with the development of DM.1 A similar mutation in SOD1 is associated with the development of familial amyotrophic lateral sclerosis (ALS; Lou Gehrig disease) in humans.

    The initial published paper showed the SOD1 mutation to be present in five breeds1; based on further testing, the American Kennel Club and the Orthopedic Foundation for Animals (OFA) recommend the following breeds be tested for DM: American Eskimo dog, Bernese mountain dog, borzoi, boxer, Chesapeake Bay retriever, German shepherd, golden retriever, Great Pyrenees, Kerry blue terrier, Lancashire heeler, poodle, pug, Rhodesian ridgeback, Shetland sheepdog, soft-coated wheaten terrier, Welsh corgi (both Cardigan and Pembroke, though it is found more commonly in Pembrokes), and wire fox terrier.2 The SOD1 mutation associated with DM has been shown to be the same in all tested breeds, making the test useful for any dog suspected of having DM.

    The Test

    The DNA test for the SOD1 mutation is available from several companies. The OFA offers the test using an FTA Card system (Whatman): the client rubs the inside of the dog’s mouth with a sponge-tipped applicator and presses it onto an FTA card, which is designed to trap and preserve nucleic acids for DNA testing. Other companies use the more conventional buccal swab system.

    Test results may be reported as “clear” (homozygous negative, or normal/normal), “carrier” (heterozygous, or normal/mutant), or “at risk” (homozygous positive, or mutant/mutant). OFA results may be notated as N/N, N/A, or A/A, with N indicating normal and A indicating affected. Homozygous-positive dogs are, unfortunately, extremely likely to develop the disease within their lifetime. Heterozygous dogs and homozygous-negative dogs will not develop familial DM, but the breeding of carrier (heterozygous) dogs should be carefully considered. In some breeds, such as the Pembroke Welsh corgi, the mutation may be so prevalent (only 10% of 1756 dogs have tested “clear” according to the OFA at the time of this writing) that the exclusion of carrier dogs from the breeding pool may be detrimental to the breed. Generally speaking, unaffected carrier animals with any known disadvantageous mutation should be considered extraordinary specimens of their breed to qualify for breeding, as they will create more carriers even if bred to a normal/normal dog.

    It is important to note that homozygous-positive dogs, like any dog, can also have other types of neurologic disease (e.g., disk extrusion, spinal tumor). Therefore, even when a dog is known to be homozygous affected for the DM mutation, diagnostics should be performed to rule out a treatable condition.

    1. Awano T, Johnson GS, Wade CM, et al. 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;106(8):2794-2799.

    2. The Orthopedic Foundation for Animals. Testing information and statistics on affected breeds. http://www.offa.org/stats.html. Accessed February 2013.

    References »

    NEXT: Equine Essentials: Blood Pressure Management in Equine Anesthesia

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