EIC: Owner Information

DYNAMIN-ASSOCIATED EXERCISE INDUCED COLLAPSE IN LABRADOR RETRIEVERS

A disorder causing exercise intolerance and collapse (EIC, now known as dynamin-associated EIC; d-EIC) occurs in Labrador Retrievers and occasionally in other breeds.

Investigators from the Western College of Veterinary Medicine at the University of Saskatchewan (Taylor, Shmon), the College of Veterinary Medicine at the University of Minnesota (Patterson,Mickelson,Minor), and the Comparative Neuromuscular Laboratory at the School of Medicine - University of California (Shelton) have been researching this condition for more than 20 years.

This group identified the causative mutation and there is now a test available to determine if dogs are affected (homozygous for the DNM1 mutation), carriers (one copy of the mutation) or clear of the mutation. Only homozygous dogs (two copies of the DNM1 mutation) are symptomatic for dEIC.
Which Labrador retrievers get it?

Dynamin-associated exercise intolerance and collapse (d-EIC) is a common inherited disorder in Labrador Retrievers. Black, yellow and chocolate Labradors of both sexes are affected.  Signs first become apparent in young dogs - usually between 5 months and 3 years of age (average 14 months).

Affected dogs exhibiting symptoms of collapse are usually described as extremely fit, muscular, prime athletic specimens with an excitable temperament and lots of drive.

How common is it?

EIC is the most common reason for exercise/excitement induced collapse in Labrador retrievers that seem otherwise normal and healthy between collapse episodes. 

Current data from the first 45,000 Labradors tested at the University of MN (as of 10/2017) shows that nearly 40% of all Labradors tested have been carriers (with one copy of the mutation: E/N) and approximately 6% of dogs have been affected (with 2 copies: E/E) and susceptible to collapse. Some dogs have been tested because of collapse, but most tests have been performed to determine EIC status for breeding purposes.  Interestingly, the prevalence of carriers is not different between field trial /hunt test dogs and show dogs and pet dogs.

Most (>80%) affected Labradors (E/E: 2 copies of the mutation) experience at least one episode of collapse by the time they are 4 years of age. Many competitive field trial dogs are unable to continue training and competing at a high level but if trigger activities can be avoided, dogs with EIC live normal lives. A few genetically affected (E/E) dogs rarely or never exhibit collapse, perhaps because they do not engage in the required strenuous activity with extreme excitement that is required to produce collapse. DNA testing is the only way to know for certain whether a dog has EIC.

Other Breeds

The research laboratory at the University of Minnesota has tested  hundreds of samples from many of the other common retriever breeds including Golden Retrievers, Flat-Coated Retrievers, Chesapeake Bay Retrievers, Nova Scotia Duck Tolling Retrievers and Curly Coated Retrievers. So far, in retrievers, the mutation has only been found in Labradors, Curly coated retrievers (40% carriers, 18% affected) and in Chesapeake Bay Retrievers (17% carriers, 3% affected).

The laboratory has also tested normal and collapsing dogs from many other working and sporting breeds. The mutation has been identified in Boykin Spaniels (33% carriers, 7% affected), Old English Sheepdogs (30% carriers, 3% affected), and rarely in German Wirehaired Pointers,  Bouvier des Flanders, Pembroke Welsh Corgis and Cocker Spaniels.

Other Collapse Disorders

Many breeds of dogs have exercise intolerance syndromes that are not caused by the DNM1 genetic mutation that causes EIC.

Our research team has been investigating a disorder called Border Collie Collapse that affects Border collies, Australian Cattle dogs, Australian Kelpies, Australian Shepherds, Shetland sheepdogs, Bearded collies, and Collies. http://z.umn.edu/bordercolliecollapse

Description of Collapse

Dogs with d-EIC can tolerate mild to moderate exercise, but 5 to 20 minutes of strenuous exercise with excitement induces weakness and then collapse.  Some affected dogs collapse whenever they are exercised to this extent - other dogs only exhibit collapse sporadically.

Typically the rear limbs become weak and unable to support weight and dogs will continue to run while dragging their back legs. Dogs develop a wide-based, long, loose stride rather than the short, stiff strides typically associated with muscle weakness.   In some dogs the rear limb collapse progresses gradually to forelimb weakness and occasionally to a total inability to move. Muscles of the rear limbs are relatively flaccid during collapse and there is loss of the patellar reflex during collapse and for a short time during recovery.  Some dogs appear to have a loss of balance and may fall over, particularly as they recover from collapse. Dogs are not painful or stiff during the collapse or upon recovery.  A few dogs have died during or immediately after an episode of exercise-induced collapse – the reason for their death has not been determined but failure to ventilate adequately and hyperthermia have been considered most likely – post mortem evaluation is normal.

Dogs worsen after exercise.   It is common for the symptoms to worsen for 3 to 5 minutes even after exercise has been terminated.  A few affected dogs have died during exercise or while resting immediately after an episode of exercise-induced collapse.  An affected dog's exercise should ALWAYS be stopped immediately at the first hint of incoordination or wobbliness.  . 

Veterinary Evaluation. Nervous system, cardiovascular and musculoskeletal examinations are unremarkable at rest in dogs with EIC as is routine blood analysis at rest and even during an episode of collapse. These dogs do not experience heart rhythm abnormalities, low blood sugar, electrolyte disturbances or respiratory difficulty during collapse.  Body temperature is remarkably elevated during collapse (average 107.1F [41.7C], many up to 108F [42.2C]), and carbon dioxide levels in their blood are very low due to extreme panting to blow off heat, but the high temperatures and degree of hyperventilation are  not different from those measured in normal Labradors without EIC who perform the same exercise.

Recovery from collapse.  Most dogs recover from EIC-collapse quickly and are normal within 5 to 25 minutes with no residual pain, weakness or stiffness. Recovery is gradual rather than instantaneous – they do not just “snap out of it”. Massage of the muscles or palpation of the joints or spine during recovery does not cause discomfort.
Factors Contributing to Collapse on a Given Day

Ambient Temperature.  Hot weather does not seem to be necessary to induce collapse, but if the temperature is very warm, collapse is more likely. Affected dogs are less likely to collapse in cold weather or while swimming, but dogs have exhibited collapse while breaking ice retrieving waterfowl in frigid temperatures and dogs have drowned when experiencing EIC -related collapse in the water.

Excitement.   Dogs that exhibit the symptoms of EIC are most likely to have intense, excitable personalities, and it is very apparent that their level of excitement plays a role in inducing the collapse.  Dogs with EIC are most likely to collapse when engaging in activities that they find very exciting or stressful. This can include retrieving or chasing live birds, participation in field trials with live birds, training drills with electric collar pressure and quartering for upland game

Type of Exercise.  Routine exercise like jogging or hiking is not very likely to induce an episode in dogs with EIC.  Activities with continuous intense exercise, particularly if accompanied by a high level of excitement or anxiety most commonly cause collapse.  Activities commonly implicated include pheasant hunting, repetitive "happy retrieves", repetition of difficult retrieves especially where the dog is having trouble finding a bird or is receiving or anticipating electric collar correction, and excitedly running alongside an all-terrain vehicle.

Body Temperature. Body temperature is normal at rest in dogs with EIC and is dramatically increased during collapse (often >41.5 C, >107.6F).  Temperatures are not different from those seen in unaffected Labrador Retrievers doing the same type and amount of exercise.  Dogs lose body heat through panting, so all dogs with these dramatic elevations in body temperature will pant hard in an attempt to cool off.  Although the elevated temperature after exercise may play a role in EIC related collapse (making dogs more dependent on dynamin1 function – see below), and may even contribute to the death of some affected dogs, inability to properly regulate temperature is not the underlying problem in dogs with EIC.

Diagnosis of EIC

Until October of 2008, EIC could only be diagnosed by systematically ruling out all other disorders causing exercise intolerance and collapse and by observing characteristic clinical features, history and laboratory test results in affected dogs. Even today, any Labrador retriever with exercise intolerance should always have a complete veterinary evaluation to rule-out

Even though EIC is the most common reason for exercise/excitement induced collapse in Labrador retrievers that seem otherwise normal and healthy between collapse episodes, there are many other reasons for Labrador retrievers to collapse.

If a Labrador has episodes of collapse or exercise intolerance they should be fully evaluated by a veterinarian for a number of treatable metabolic, cardiac and neurologic disorders including low blood sugar, low blood cortisol, electrolyte abnormalities, heart failure, cardiac arrhythmias, pulmonary hypertension, respiratory disorders, cauda equina syndrome, muscle disorders and epilepsy.

If the dog has collapse episodes typical of EIC that are always associated with strenuous exercise, and the dog is completely normal between episodes of collapse and is determined to be genetically affected (homozygous E/E), then EIC may be the reason for their collapse. If they have other symptoms, have collapse episodes that are not typical for EIC or that occur unassociated with exercise or if they test genetically EIC clear or as an EIC carrier then EIC is not the reason for their collapse – full veterinary evaluation is warranted.

Genetic (DNA) testing can now be easily performed to confirm a suspected diagnosis of EIC. 

GENETICS

In 2007 the genetic mutation responsible for susceptibility to d-EIC was identified. This is a mutation in the gene for dynamin-1 (DNM1), a protein expressed only in the brain and spinal cord where it plays a key role in repackaging synaptic vesicles containing neurotransmitters. DNM1 is not required during low level neurological stimulation, but when a heightened stimulus creates a heavy load on release of CNS neurotransmitters (as with intense exercise, a high level of excitement or perhaps increased body temperature), DNM1 is essential for sustained synaptic transmission in the brain and spinal cord. Dogs with 2 copies of the d-EIC mutation (EE) are susceptible to collapse in those conditions.Testing

DNA testing for the genetic mutation causing EIC susceptibility can now be performed. This is a reliable test for the actual mutation (not linkage) so results are definitive and accurate — determining with certainty whether a dog has one copy of the mutation (E/N: carrier), two copies of the mutation (E/E: affected) or no copies of the mutation (N/N: clear).

Instructions for collecting and submitting samples for testing, sample shipping and the necessary forms are available on the website of the Veterinary Diagnostic Laboratory at the University of Minnesota. In addition to testing blood samples, cheek swabs can be submitted by veterinarians from adult dogs or weaned puppies, and litters of newborn puppies can be tested by sending in dewclaws. Frozen stored semen can also be tested from deceased sires.

TESTING

DNA testing for the genetic mutation causing EIC susceptibility can now be performed. This is a reliable test for the actual mutation (not linkage) so results are definitive and accurate - determining with certainty whether a dog has one copy of the mutation (E/N: carrier), 2 copies of the mutation (E/E: affected) or no copies of the mutation (N/N: clear). Instructions for collecting and submitting samples for testing, sample shipping and the necessary forms are available on the website of the Veterinary Diagnostic Laboratory at the University of Minnesota. In addition to testing blood samples, cheek swabs can be submitted by veterinarians from adult dogs or weaned puppies, and litters of newborn puppies can be tested by sending in dewclaws. Frozen stored semen can also be tested from deceased sires.

http://www.vdl.umn.edu/services-and-fees/canine-neuromuscular/canine-exercise-induced-collapse-eic/index.htm

Owners of potential breeding dogs should be encouraged to obtain OFA (http://www.offa.org/search.html) certification to document their test results and make them available to others who might be interested in breeding to their dogs.  If a dog does not have their EIC result listed on OFA, you should ask the owner to provide you with a copy of the laboratory result they obtained.

WHAT IS THE IMPACT OF THE MUTATION?

Most (>83%) affected Labradors (EE) experience at least one episode of collapse by the time they are 4 years of age.  Most competitive dogs are unable to continue training and competing at a high level. If trigger activities can be avoided, dogs with d-EIC live normal lives. 

A few EE dogs never exhibit collapse, perhaps because they do not engage in the required strenuous activity with extreme excitement as required to produce collapse. DNA testing is the only way to know for certain whether a dog has dEIC.  Dogs that are carriers for the dynamin-1 mutation are clinically normal and have no exercise intolerance.

It is important that owners of dogs with EIC be made aware that the dog's exercise should be stopped at the first hint of incoordination or wobbliness as some affected dogs have died during collapse when their owners allowed or encouraged continuing exercise.  Not all of the EIC deaths have occurred in dogs rated as severely affected based on their historical number of episodes of collapse or the amount of activity required to induce previous episodes of collapse.

TREATMENT

The best treatment consists of avoiding known trigger activities and activities that involve intensive exercise in conjunction with extreme excitement especially in hot weather.  A few d-EIC affected male dogs have experienced improvement after neutering - with an improved ability to tolerate intensive exercise without collapse.  Early in our evaluation of dogs with dEIC, Phenobarbital treatment may have resulted in similar improvement in some dogs. Our impression is that improvement with both of these treatments may have simply been a result of a decrease in the general excitement level of the dog.

COLLAPSING LABRADORS THAT DO NOT HAVE EIC

Occasionally we hear about dogs experiencing recurrent episodes of incoordination or collapse with exercise that are not EIC affected – they are either EIC carriers (E/N) or EIC clear (N/N).  In many cases there are abnormal physical findings detected at rest (heart murmurs, muscle atrophy, pain, etc.) helping to distinguish these dogs from dogs with EIC-related collapse.  In others the collapse episodes are subtly different from EIC-related collapse. For example, the age of onset may be older, the episodes may be more sudden in onset (not progressive as exercise continues), the episodes may be very brief (1-2 minutes instead of 10 or 15 minutes), the episodes may involve all 4 legs at once (instead of rear legs first), muscle tone may be increased (instead of decreased), mentation may be abnormal (instead of normal), systemic signs may be evident (unlike EIC), or affected dogs may seem painful during an episode (unlike EIC). The episodes of exercise intolerance in these dogs can be attributed to a number of different disorders including joint pain, heart failure, pulmonary hypertension, anemia, heart rhythm disturbances, laryngeal paralysis, lung disease, low blood sugar,  low blood cortisol, cauda equina syndrome, myasthenia gravis, and muscle disease.

It appears that one of the most common disorders causing episodes of exercise intolerance or collapse after exercise that can be confused with EIC in Labrador retrievers is an atypical seizure disorder.

Atypical Seizures / Paroxysmal Dyskinesia. An episodic movement disorder that may be a form of focal motor seizure has been recognized in Labrador Retrievers.  We have been collecting questionnaires and DNA samples from collapsing Labradors for 6 years now and we believe this is a common disorder in the breed.  This disorder has been called atypical epilepsy, paroxysmal dyskinesia or episodic dyskinesia. We believe that most Labrador retrievers presenting with these episodes have idiopathic epilepsy.  The episodes in some dogs are most likely to occur upon waking or being startled, but in many dogs episodes seem to be triggered by exercise, excitement or hyperventilation, leading to confusion with EIC.  Signs are different, however, from typical EIC episodes. Some dogs simply stagger and look dazed or confused for a few seconds or minutes and then recover, without ever falling over.  Others have a 2 to 5 minute episode (occasionally longer) where they appear anxious and are unable to stand erect and walk but are able to crawl to their desired location. Some dogs seem to have a severe loss of balance during episodes.  Affected dogs maintain consciousness and can obey commands during episodes. Some dogs have a dramatic decrease in their episode frequency when treated with chronic oral anticonvulsant therapy and some affected dogs develop more classical generalized tonic-clonic (loss of consciousness, falling to their side, paddling) seizures later in life.

Heat exhaustion / Heat stroke. Before we were able to test for and diagnose EIC, there were many who felt that EIC collapse episodes were simply a manifestation of recurrent heat exhaustion or heat stroke.  The collapse episodes we see in dogs with EIC are, however, very different from collapse episodes associated with heat stroke.  Heat stroke severe enough to cause collapse in a dog is life-threatening. Recovery, if it does occur, is slow and prolonged (hours to days) even with intensive treatment. Many affected dogs progress to kidney failure and death.  Laboratory evaluation reveals a dramatic increase in the muscle enzyme CK. Mentation changes that are severe, progressive and persistent (for hours to days) occur in 80% of dogs collapsed due to heat stroke. Significant blood vessel wall injury leads to blood clots forming within blood vessels, disseminated intravascular coagulation (DIC), low blood platelets and damage to multiple organs.  In contrast, dogs with EIC-related collapse show no laboratory abnormalities and they recover quickly - happy and running around within 5 to 25 minutes.  Besides the severity of collapse episodes, the recurrent nature of EIC-related collapse and the fact that collapse can occur even on days with moderate or cool ambient temperatures helps to distinguish EIC from heat-related illness.

IMPORTANT EIC FACTS

1.  EIC is the most common reason for exercise and excitement induced collapse or wobbly gait in Labrador retrievers that seem otherwise normal and healthy.

2.  Most dogs with EIC exhibit a characteristic pattern of collapse starting with rear limb weakness. They may continue to walk or run while dragging their back legs.  EIC collapse progressively worsens as the dog continues to exercise and may even continue to worsen for a few minutes after exercise is halted.

3. All exercising Labrador retrievers will have high body temperatures after strenuous activity.  It is not unusual for both EIC affected dogs and EIC unaffected dogs to have temperatures greater than 107 F (41.7C) after 10 minutes of retrieving.

3. EIC-related collapse is not painful and typically resolves after 5-25 minutes of rest.

4. A severe episode of EIC collapse can be fatal.

5. Most (>80%) dogs that have EIC are observed to collapse at least once before the age of 3 years.  A few genetically affected dogs never collapse – probably because they never experience the right mix of exercise and excitement.

6. Activities involving continuous intense exercise with excitement or stress are most likely to trigger episodes of EIC-related collapse.

6. The only way to know for certain whether or not a dog has EIC is through DNA testing.

7.  A mutation in the gene for dynamin-1 (DNM1) causes susceptibility to EIC.  EIC is an autosomal recessive inherited trait, meaning that to be affected (and susceptible to collapse) a dog must have two copies of the mutant gene – one inherited from each parent. 

8. DNA testing for the DNM1 mutation can be performed on cheek swabs, blood, or puppy dewclaws. Results will determine whether a dog has EIC (2 copies of the mutation: E/E), is a carrier of EIC (1 copy of the mutation: E/N), or is clear of the mutation (N/N). 

9. Results from EIC testing can easily be posted on the Orthopedic Foundation for Animals website (www.offa.org) along with hip, elbow, eye and CNM certifications, making the results available to breeders evaluating the suitability of listed dogs for breeding purposes.

Scientific References:

A canine dynamin 1 mutation is highly associated with the syndrome of exercise-induced collapse.
Patterson EE, Minor KM, Tchernatynskaia AV, Taylor SM, Shelton GD, Ekenstedt KJ, Mickelson JR.
Nature Genetics 2008; 40(10): 1235-1239

Exercise Induced Collapse of Labrador Retrievers: Survey results and preliminary investigation of heritability.
Taylor SM, Shmon CL, Shelton GD, Patterson EE, Minor K, Mickelson JR.
Journal of the American Animal Hospital Association, November 2008; 44: 295-301

Exercise-induced Weakness/Collapse in Labrador Retrievers
Taylor SM.
In LP Tilley and FW Smith (eds), 2016, Blackwell's Five Minute Veterinary Consult: Canine and Feline (6th edition). 472-3.

Evaluations of Labrador Retrievers with Exercise Induced Collapse, including response to a standardized strenuous exercise protocol.
Taylor SM, Shmon CL, Adams VJ, Mickelson JR, Patterson EE, Shelton GD.
Journal of the American Animal Hospital Association, January 2009.

Exercise intolerance in retrievers.
Cosford KL, Taylor SM.
Veterinary Medicine, February 2010; Vol 105 No 2:64-75.

Presence and impact of the exercise-induced collapse associated DNM1 mutation in Labrador retrievers and other breeds.
Minor, K.M., Patterson, E.E., Keating, M.K., Gross, S.D., Ekenstedt, K.J., Taylor, S.M., Mickelson, J.R., 2011.
The Veterinary Journal. doi:10.1016/j.tvjl.2011.06.022.

Relationship between dynamin 1 mutation status and characteristics of recurrent episodes of exercise-induced collapse in Labrador Retrievers.
Furrow, E, Minor, K.M., Taylor, S.M., Mickelson, J.R., Patterson, E.E., 2013.
J AM Vet Med Assoc, No. 6, March 15, 2013: 786-791.

Dynamin-Associated Exercise Induced Collapse in Labrador Retrievers.
Taylor SM.
In Cote, E. Clinical Veterinary Advisor Dogs and Cats, 4th edition, Elsevier, 2017.

Updated December 2017