EIC (exercise-induced collapse)

EIC (exercise-induced collapse) is a recently recognised neuromuscular disorder of increasing significance in Labrador Retrievers, especially those dogs used for hunting and field trials. Recent research at the University of Minnesota has identified the gene responsible for the condition known as EIC. A mutation in the canine dynamin 1 (DNM1) gene is very likely to be fundamentally responsible for EIC. The syndrome of Exercise Induced Collapse (EIC) is manifested by muscle weakness, incoordination and life-threatening collapse after intense exercise. Five to fifteen minutes of strenuous exercise causes dogs suffering from this condition to develop a „wobbly“ gait, which soon progresses to nonpainful, flaccid paraparesis and a loss of control of the rear limbs. The episode may progress to all four limbs. Collapse episodes usually last for 5-10 minutes, and after 30 minutes there is often complete recovery, but episodes are occasionally fatal. The rectal temperature of dogs during an episode typically reaches 41.7°C (from a resting temperature of 39°C). The DNM1 mutation that affects the function of the dynamin 1 protein can be detected by a mutation-based direct DNA-test. We have designated the letters EIC to indicate the mutant form or EIC form of the DNM1 gene and N to indicate the normal form of this gene. EIC is inherited as an autosomal recessive trait. So there are three conditions a dog can be: it can be clear (genotype N/N or homozygous normal) meaning that it does not carry the mutation and will not develop EIC. Since it also cannot pass the mutation onto its offspring, it can be mated to any other dog. A dog which has one copy of the gene with the mutation and one copy without the mutation is called a carrier or heterozygous (genotype N/EIC); while it will not be affected by EIC, it can pass the mutation onto its offspring and should therefore only be mated to clear dogs. Dogs that develop EIC have two gene copies with the mutation (genotype EIC/EIC or homozygous affected); they will always pass the mutated gene onto their offspring and should also be mated only to clear dogs. By DNA testing, the responsible mutation can be shown directly. This method provides a test with a very high accuracy and can be done at any age. It offers the possibility to distinguish not only between affected and clear dogs, but also to identify clinically healthy carriers (N/EIC). This is an essential information for controlling the disease in the breed, as carriers are able to spread the disease in the population, but can not be identified by means of common laboratory diagnostic. The DNA test does not provide information about onset of clinical signs and the severity of disease symptoms. Approximately 96% of the N/EIC dogs have no signs of EIC or any type of collapse, while approximately 4% have been reported to show some signs of collapse or intolerance associated with exercise. The vast majority of these collapses can be attributed to other medical conditions, or their signs are not consistent with the classic signs of EIC that starts with wobbliness in the rear legs. Similarly, approximately 5% of all dogs with the N/N genotype are reported by owners to show some signs of an exercise-associated weakness or collapse. Again, this is likely due to other causes and is not classic EIC (e.g. CNM Myopathy). The discovery of the EIC gene and its mutation will provide breeders and veterinarians with a non-invasive test for diagnosis, and a selection method for designing matings that can limit the production of affected dogs.