Exercise Induced Collapse (EIC)
Written by Dr. Emily Morgan BSc, DMV
Exercise Induced Collapse (EIC) is a genetic neuromuscular disease of dogs seen in retriever breeds (Labrador, Chesapeake Bay, Curly-Coated Retrievers) as well as several other breeds such as the Old English Sheepdog and Welsh Corgi Pembroke. As the name suggests, the disease involves physical collapse precipitated by exercise.
Clinical signs of EIC
Episodes (symptoms) of EIC first appear when a young dog enters heavy training, usually between 5 months to 1 year of age. Normal exercise does not stimulate an episode, whereas 15 to 20 minutes of intense exercise and excitement will. Signs of an episode include limb weakness (particularly of the hindlimbs), ataxia and collapse. Pain is not a feature and dogs remain mentally alert during episodes. Following an episode, dogs in most cases return to normal physical status, usually within 60 minutes. Occasionally, episodes of EIC can be fatal.
Susceptibility and Transmission
EIC is a recessive genetic disease, meaning that an individual with two copies of the mutated gene (M/M) is at risk of developing symptoms. Furthermore, the disease is autosomal, meaning that either sex can be affected.
Both parents of an affected animal must be carriers (M/N); they each have one copy of the mutation. EIC is said to have variable penetrance as not all individuals with two copies of the mutated gene (M/M) present episodes of collapse. However, this may be due to the fact that some of these dogs have not experienced exercise or excitement that is intense enough to trigger an episode.
Genetic profile of EIC
The mutation that is the cause of EIC is a simple substitution of one DNA letter (base) for another. Specifically, at position 767 of the DNM1 gene, a G is replaced by a T. The DNM1 gene codes for the Dynamin-1 protein, and when the gene is mutated, a non-functional Dynamin-1 protein is produced. The Dynamin-1 protein plays an important role at the neuromuscular junction where it is involved in the transmission of nerve signals to the muscles. The Dynamin-1 protein is required for the recycling of neurotransmitter molecules via endocytosis (recovery) of the synaptic vesicles that contain the neurotransmitter.
In dogs that are homozygous mutant (M/M), with a defective Dynamin-1 protein, normal activity and even mild exercise will not present a problem. However, strenuous exercise in these dogs results in a situation of over demand but under supply of neurotransmitter and a failure of nerve signal transmission to the muscles. This precipitates the physical collapse seen in EIC.
Individuals that are homozygous for the mutant allele (M/M) are at risk of developing EIC, depending on the level of exercise. Individuals that are heterozygous (M/N, carrier) do not present increased risk of collapse. This in turn suggests that having one good copy of the DNM1 gene is sufficient to supply enough functional Dynamin-1 protein to prevent collapse during moderate to intense exercise. If carrier animals are used for reproduction, the mutated version of the DNM1 gene can be passed on to future generations.
Preventative Genetic Testing Available
DNA testing is available to detect the mutation responsible for EIC. This is accomplished by DNA recovery, usually from a buccal swab or a blood sample, followed by amplification and sequencing of the mutation site.
Dogs that experience episodes of collapse following exercise can be tested to identify homozygous mutant individuals (M/M) and to diagnose a predisposition to EIC. Individuals with breeding potential can be screened to detect carrier (M/N) animals and to identify clear (N/N) animals. A carrier animal (M/N) with otherwise good genetics is still useful in breeding programs if it is bred to a clear (N/N) animal. In a clear (N/N) by carrier (M/N) mating, on average half of the puppies born will be N/N (clear) for EIC and half will be M/N carriers. Importantly, no puppies will be M/M double mutant at risk of the disease. This method of breeding will reduce the prevalence of EIC within the susceptible breeds.
Mutation frequencies
Samples for EIC testing received by Labgenvet come from both veterinary clinics and from breeders. The DNA profiles for N/N (clear), M/N (carrier) and M/M (double mutant, at risk) samples received are given, as well as the overall percentages of these cases, as follows:
These results can be further broken down for specific breeds:
Limited testing in several additional breeds (Belgian Shepherd, Gordon Setter, English Cocker Spaniel, Boykin Spaniel) have to date provided N/N (clear) results.
References:
- Furrow E, Minor KM, Taylor SM et al. (2013) Relationship between dynamin 1 mutation status and characteristics of recurrent episodes of exercise-induced collapse in Labrador Retrievers. J Am Vet Med Assoc. 15;242(6):786-91. [pubmed/23445289]
- Minor KM, Patterson EE, Keating MK et al. (2011) Presence and impact of the exercise-induced collapse associated DNM1 mutation in Labrador retrievers and other breeds. Vet J. 189(2):214-9. [pubmed/21782486]
- Patterson EE et al. (2008) A canine DNM1 mutation is highly associated with the syndrome of exercise-induced collapse. Nature Genetics 40(10) :1235. [pubmed/18806795]