Canine Epileptoid Cramping Syndrome (CECS) and Shaking Puppy Syndrome (SPS)
Various reports on social media have raised the profile of two neurological problems in the Border Terrier. What follows are comments to aid those who may either have a dog with one of these problems or may be worried about the future health of the breed. If you wish to help find solutions to either of these issues then it would be best to work through the Breed Clubs and in particular myself as Breed Health Co-ordinator as it is important we speak to the research community and veterinary profession through one channel. Fund raising is going on but at this time please be aware this is not with the sanction of any breed club. Funding is frankly not the issue at this moment in time.
As Breed Health Co-ordinator I discussed the CECS problem with two groups. A major step forward has been achieved in searching for the genetic markers for CECS by the Breed Clubs' supporting the sequencing of the Border Terrier genome at the AHT. This alongside genome sequencing for around 75 other breeds will provide a useful platform for locating mutations related to neurological function. However this is a step forward but not yet a solution. We will need to agree the top three conditions in our breed and this is in progress. Once this work is completed we can expect progress towards identifying any genetic mutations of health significance.
There are four steps towards good research into inherited illnesses.
1. Accurate diagnosis of an affected dog’s condition. This is best achieved in the first instance by seeking the opinion of a suitable qualified specialist. In the case of CECS and SPS this would be a recognised neurologist.
2. Report the diagnosis to the breed health co-ordinator. Health survey forms are available on the various Club websites and completion of one of these forms along with full information about your dog’s condition should be forwarded to me (firstname.lastname@example.org).
3. Establish a single route to the research community. Using the breed clubs' Breed Health Co-ordinator is the recommended method for achieving the buy in of the research and veterinary community. It also keeps the breed engaged as a whole.
4. Sample collection from individual dogs is an important part of the process at a later stage. We will use the AHT for this as they are the KC's centre for genetic research. Further information will follow when and how these samples should be collected and forwarded.
It is important to understand that the genetic research requires careful co-ordination if we are to make useful progress. Involving a wide range of individuals without an agreed plan is unlikely to be efficient in producing results and is most likely to create competition and confusion among the research community. Hence the request that these things should be routed through me as Breed Health Co-ordinator.
This condition was first recognised in mainland Europe and America. It is likely the close breeding of a limited number of British lines brought this condition to the fore. Once discovered abroad the condition started to be reported in the UK. At the outset it was argued to be a gastric or muscle cramp but we have now come to accept the neurological origins of CECS. It is highly likely this condition has been present in the breed for a very long time but became increasingly prevalent in closely bred lines developed in the 1980s.
Neurological seizures have a prevalence of around 4-5% in borders. This is confirmed by our own breed survey in the UK and the breed surveys carried out by the Kennel Club in 2000 and 2015. Seizures are reported in dogs from around 4-5 years of age. Deaths linked to seizures are reported across a broad age range from 5 through to 15 years with a median age in excess of 10 years. CECS was reported specifically on the 2015 KC survey at a prevalence rate of 1.6%.
One of the challenges in dealing with CECS has been the development of specific diagnostic advice and the situation remains that there is no reliable confirmatory diagnostic test. We are therefore relying upon expert diagnosis based on symptomology alone. Typically CECS is characterised by abnormal behaviour (anxiousness, distracted attitude, lip licking) leading to a seizure type episode where the dog appears to remain conscious of its surroundings. The seizure appears in many cases to be associated with muscle spasm, loss of balance and occasionally gastric noise and probably discomfort. Once recovered dogs appear entirely normal.
These symptoms have been recorded and various video clips are available on-line. There is considered to be some similarity between CECS and Scottie Cramp and other similar cramping syndromes in a number of other terrier breeds.
A genetic predisposition has been conjectured for some time but despite various international teams promising 'progress soon' - in fact nothing has been forthcoming. This is quite possibly because of a lack of any co-ordinated effort between the various research groups and the lack of reliable diagnosis. This is reflected by the low number of scientific publications on this specific condition.
In the interim, further work is planned to investigate a correlation with diet related factors (gluten sensitivity) which may also aid the search for a diagnostic test and identification of genetic mutations. However given the range of non-specific symptoms and the disorganised way in which many dogs have been diagnosed as suffering from CECS there is every possibility that we are dealing with a number of mutations rather than single gene defect. The prospect of finding a suitable gene test remans an ambitious end point which will be difficult to achieve without carefully co-ordinated research.
Shaking Puppy Syndrome
SPS has been recently reported but even less is published on this condition in Border Terriers. It is a recognised condition in the Weimaraner breed where it is linked to a lack of myelin around nerve pathways. Puppies tend to improve as they mature. This is related to a known gene mutation in Weimaraners and a test exists to identify affected, carriers and clear dogs.
On-line videos suggest the uncoordinated tremors in Weimaraners is similar to that seen in Border Terriers as puppies but the Borders appear to be older. There is speculation that this is the same problem as CECS but this is as yet unconfirmed. In my view we would be very fortunate to find this syndrome has the same genetic basis as CECS as a single solution would resolve both conditions.
Regrettably this condition remains as a discussion on social media and has not been reported in any detail to me as Breed Health Co-ordinator and so no estimates of prevalence can be made.
If the breed wishes to make progress with inherited conditions it is important we develop the discipline to report emerging conditions to the Breed Health Co-ordinator. The system for doing this has been in place for at least 25 years. Furthermore it is important to realise that mutations are a fact of life and pedigree breeding has a tendency to amplify the emergence of autosomal recessive conditions, yet rapid action can limit this if the gene mutation can be identified. Complex inheritance is more difficult to over-come and it is possible this is the case with CECS.
Central reporting is the only way forward unless we are to degenerate into a ‘blame culture’ approach which is entirely destructive and rarely produces the best result.
I will state for the record that the system of reporting we currently have in place is confidential and effective but it relies on owners to use it and requires the breed to promote its value.
Prof Steve Dean BVetMed, MRCVS, DVR
Border Terrier Health Co-ordinator
Further comments on Shaking Puppy Syndrome (SPS) June 2016
by the Border Terrier Breed Health Co-ordinator
As a follow up to earlier comments on SPS, I understand much has been said on social media and what follows is intended to provide Border Terrier owners with further advice and guidance on progress to date.
It would appear some people are claiming to hold significant amounts of data on litters where SPS has arisen. If this is correct, this is important information which needs to be made available to those with experience in identifying emerging inherited diseases. Furthermore those experts need to be engaged in the research and funded correctly or the progress will stall or fail.
Until this data is made widely available little can be done and I once again urge anybody who has direct information to release it without further delay. It is impossible for either myself as Breed Health Co-ordinator or the breed clubs themselves, to make statements regarding SPS if the condition is not being properly reported. As BHC I have received a few snippets through third party reports of affected litters but despite asking for further information this has not been forthcoming.
What do we know at this stage?
A published Case Study from the Ohio State University, Columbus reports upon four cases of tremors in young Border Terrier puppies. The information on these pups was reported by researchers and clinicians from Missouri and the Norwegian Veterinary School in Oslo. There is much useful and detailed pathology in the paper, as this work has been entirely based on post-mortem examinations of euthanased pups.
In summary the report suggests this is the first recorded appearance of a degenerative spongiform change of myelin in white matter of the brain, principally in the cerebellum, brainstem and spinal cord and to a lesser extent in the thalamus and cerebral hemispheres. This provides the descriptive term Spongiform Leuco-Encephalo-Myelopathy (now being shortened to the acronym SLEM). Myelin provides insulation around nerve fibres and any serious defect in the formation of the myelin sheath is likely to lead to poor transmission of nerve impulses and therefore neurological symptoms.
The symptoms reported include uncontrolled tremors and incoordination of hind limb movements which was consistent with the areas of the spinal cord that were affected. The pups were around three to four weeks of age when presented for euthanasia and the tremors were first noted when the pups started to walk. The Scandinavian pups were reported as becoming progressively worse over time.
The authors note the similarities and differences between this condition and other myelin sheath degenerations in other types of dog where perhaps the most well known is the shaking puppy condition in the Weimaraner. However it would appear pathologically the sites of the brain most affected and the microscopic appearance of this myelin degeneration in Border Terriers is unique.
As a common male ancestor was found in all four pups (bearing in mind one was from a US breeder, two were presented at Uppsala in Sweden and the fourth at the Oslo Vet School) a genetic mutation is considered possible. The US pup was male and the others were female.
As this condition has some similarities with a human condition (Canavan’s disease), which is known to be an autosomal recessive gene mutation, the authors speculate how this might be a single gene autosomal recessive mutation leading to defective myelin production.
The Case Report was accepted for publication in late 2011 and therefore it is likely these pups were first presented in either 2010 or the early part of 2011.
There is much in this report that requires further work but of course the first question is the likelihood that the cases of SPS being seen in the UK are the same condition. Given the circumstances and the fact that the common ancestor was born in 1975 we can only hope that this is so. Of course other congenital myelin defects are reported in other breeds and this raises the possibility of another mutation. However the working assumption that we are dealing with the same inherited condition in the UK is valid for the time being, especially as the common ancestor from 1975 is likely to be a British dog although this is not stated.
Further work is apparently underway
Why has this condition taken so long to surface here in the UK? The fact that the common ancestor was born in 1975 does not in fact mean this was the first time the mutation occurred as this could have happened even further back in history. If we are fortunate enough to have a single mutation identified and it proves to be autosomal recessive, then we will have the basis for a useful gene test to assist us in dealing with this neurological condition. Until then we have to rely on more traditional methods.
Currently the hypothesis proposed suggests a single recessive gene defect. To produce affected pups requires that both parents will be carriers of the mutation. Their mating will theoretically produce 25% clinically affected pups; 50% carriers; and 25% clear. The carriers and the clear pups will be clinically unaffected. In addition both parents although carriers, will be clinically normal too.
This is consistent with the Ohio Case Report as littermates of the affected pups were clinically normal as were the parents. It would be very helpful to know how many litters are known for certain to have been affected in the UK along with their pedigrees and how many pups in each were clinically affected.
The distribution of carriers from the original source of the mutation would not have been known at that time, but further pedigree analysis might reveal how extensive the spread of the mutation may be within our breed in the UK. It is quite possible that the original mutation pre-dates the identified source of the problem in the Ohio report but even if this proves incorrect there is a very real chance of being able to control further spread of the mutation if pedigree analysis can be completed quite soon.
Clinically affected animals will have arisen as a result of in-breeding as this would bring together male and female carriers several generations onwards from the original source of the mutation. Specific advice can be generated for a breeder who is unfortunate enough to have a dog or bitch that proves to be a carrier and this does not necessarily mean that either or both must be removed from the gene pool. Sadly this a mistake many have made in other breeds in the past thus creating a significant reduction in the available gene pool and a greater risk from in-breeding as a result.
One aspect of this condition which can be viewed as encouraging is the onset of clinical signs of SLEM at around three weeks of age. This allows any action to be entirely in the breeder’s hands and avoids new puppy owners buying pups that develop the problem. Healthy litter-mates can be sold with breeding endorsements which can be removed in cases where a suitable breeding strategy can be identified.
However, before any of this can be achieved breeders need to be able to recognise the symptoms. The onset of tremors in pups as they commence to walk is a primary feature. Tremors predominantly affect the hindquarters but also the head and fore-quarters too. The tremors cease when the puppy sleeps.
Eliminate other conditions
There are other conditions that may cause pups to shake or suffer tremors and these will need to be recognised to eliminate other causes. Infection or inflammation of the cerebellum, congenital defects in the development of the cerebellum and neonatal cerebellar ataxia are all possible alternative causes but these will all have a variety of differentiating clinical signs.
Finally we need to record the litters and collect the pedigree data. This is relatively easy to achieve and the Health Co-ordinator is the logical focal point for data collection.
It is not too late to provide information about past litters as described above.
Keep calm and promote co-operation
The common sense approach is to remain calm and not seek to apportion blame. I doubt anybody intended to breed a litter with affected pups, and as both parents would be healthy there would be little evidence to help a breeder anticipate trouble. If the information is supplied we can arrange to assist the breed in future selection of breeding pairs to try and control the spread of this condition.
I would also recommend we resist speaking in riddles about any perceived historical sires that could be the source. I have had at least three suggested to me but these all post date the 1975 source mentioned in the Ohio report. So they may be carriers but they are probably not the root of the problem.
What is needed is more co-operation and informed, constructive advice and can we please cease the ‘disgusted of Stoke Poges’ type of on-line media formats.
How we find a solution to the challenges of social media is certainly not an issue for your Breed Health Co-ordinator, but it would be good if, as breed supporters, we could cease the cloak and dagger approach and deal in defensible facts that are made widely available.
In the interim the AKC Canine Health Foundation has granted some money to Missouri Vet School to conduct a search for the gene or genes involved and I will provide further updates on this work when information becomes available.
Finally I understand there has been some criticism that the Border Terrier breed clubs have supported the ‘give a dog a genome’ project, describing this as a historical venture. Well the source of the SLEM problem is historical and unravelling these historical factors will aid us in finding a potential solution. However the AHT genome project is about the future not the past, and readers will be interested to know that sequencing the entire genome of an affected dog is part of the genetic programme at Missouri. So the genome project is likely to be a significant part of the solution for breeding borders without SLEM as a risk.
If you wish to contact me I can be reached on 01628 782787 or email@example.com. I have been collecting confidential information for a very long time and I can assure you that I will keep personal details entirely confidential and will not seek to embarrass or offend anybody.
Prof Steve Dean BVetMed, MRCVS, DVR
Border Terrier Breed Health Co-ordinator
June 6, 2016