Ataxia in BSDs – The Belgian Shepherd Health Project

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Ataxia in Belgian Shepherds

by Kate Hogan, Ph.D.

History of Ataxia in Belgian Shepherds

Ataxia has a long history in the Belgian Shepherd breed, particularly in the working bloodlines. After seeing a litter of Malinois with 3 affected puppies while visiting some of the most famous Malinois breeders of the 1980s, Volker Riedel wrote in a letter that he was told, “A good Malinois breeder either has a river behind the house or a rifle in the kennel.”¹ From that time until 2012, breeders would occasionally have litters with puppies that seemed to start regressing around 6 weeks of age and would inevitably die or be euthanized by four months. It was considered the price that you might have to pay to breed on certain lines. There is some debate about how open breeders were with this information at that time, but by 2012 or so, it was not openly discussed.

In May of 2012, Mareike Wollschläger, a German breeder, had a Malinois litter that began to suffer from ataxia. She did what seems obvious today but was still pretty new in 2012: she documented the progress of that litter on her website, including publishing very difficult to watch videos of puppies clearly suffering some serious neurological problems^{2, 3}. It is probably fair to say that the Belgian Shepherd community, as a whole, did not respond in a positive or supportive way. However, Mareike persisted, and because of her efforts we now know a great deal more about ataxia.

Fortunately, several individuals in the breed provided support to Mareike and leadership to help the breed move forward in a more positive way. These individuals, some of whom had also experienced the impact of ataxia, were able to combine resources and information, and provided pivotal information and samples to the University of Bern. Their efforts led directly to the identification of the mutations that cause what is today known as spongy degeneration with cerebellar ataxia forms 1 and 2 (SDCA1 and homozygous for either of the 2 mutations known to cause it.">SDCA2) and the development of tests for both mutations^4,5. Today, testing for SDCA1 and SDCA2 is becoming more common across the world and will likely be required soon in some countries.

Current Status

Today we know that there are at least 3 forms of ataxia – 2 that have been linked to specific genetic mutations of different proteins and at least 1 other form that has not yet been identified. Unfortunately, since these mutations have only recently been discovered (2016 or 2017), there is little information about the frequency of the mutation in the breed. Original publications indicated that it could be present in 15-20% of working line Malinois and Tervueren, but the sample size was quite small in both studies ^4,5.

Interestingly, the two forms of SDCA affect different proteins involved in regulating the resting membrane potential in cells of the cerebellum. What does that actually mean? In cells it is important to maintain a separation between the external environment around the cell and the internal environment within the cell. This is especially important for cells in nervous tissue, because that’s part of how they function – by the coordinated exchange of ions on the outside of the cell with those on the inside of the cell. When this happens in a very fast, coordinated manner it is called an action potential. But in order to fire another action potential, the cells must return to their normal resting state. There are a whole host of ion channels and transporters that are responsible for that process. For puppies carrying 2 copies of either SDCA mutation, proteins that play a crucial role in that process are critically damaged as a result of either mutation and don’t function properly. So, just as these puppies are starting to develop and form the normal cellular communication pathways that are essential for coordination, the cells in the cerebellum are increasingly unable to function normally and begin to die. The progression of the condition results in worsening symptoms and death by 2 – 4 months in all affected puppies.

Types of Ataxia

Spongy degeneration with cerebellar ataxia, type 1 (SDCA1)⁴:
- The first neurological symptoms begin to develop around 4 weeks. Affected puppies lag behind their littermates in developing motor skills and begin to lose coordination, especially in the hind limbs. Eventually, puppies lose the ability to coordinate their movements at all. A typical example of this would be inability to walk in the direction of the food bowl, sometimes even walking in the opposite direction.
- Caused by a single point mutation in the KCNJ10 gene which codes for an inward rectifying K⁺ channel found in the central nervous system (brain and spinal cord), eyes, ears and kidneys.
- The first scientific article regarding SDCA, type 1 was published in 2011 and concluded that it was inherited in an autosomal recessive manner⁶.
- Researchers at the University of Bern were able to identify a mutation that was causative for the condition and developed a test to detect that mutation by the end of 2016.
- Their results were published in February 2017.
- The SDCA1 mutation was also identified in 43 of 176 Malinois control dogs, 0 of 25 Groenendael control dogs, 0 of 2 Laekenois control dogs, 1 of 33 Tervueren control dogs (this particular dog was born in a litter of Malinois) and 0 of 486 control dogs of other breeds.
Spongy degeneration with cerebellar ataxia, type 2 (SDCA2)⁵:
- Very similar to SDCA1 with a few notable differences:
  - Age of onset of symptoms may be more variable, normally around 4 to 6 weeks
  - More likely to exhibit seizures
  - More likely to also include blindness, pacing and circling behaviors
- Caused by the insertion of a 227 base pair sequence into the ATP1B2 gene which codes for a beta-subunit of the Na⁺/K⁺-ATPase found in cerebellar and brain stem tissues.
- Researchers at the University of Bern also discovered the mutation associated with SDCA2. In their original research that led to the discovery of the mutation for SDCA1, there was another group of affected animals that did not have that mutation. Part of that group of puppies with ataxia would all have the same mutation that has come to be known as SDCA2.
- Their results were published in August 2017.
- The SDCA2 mutation was also identified in 38 of 199 Malinois control dogs, 1 of 24 Groenendael control dogs, 0 of 2 Laekenois control dogs, 7 of 28 Tervueren control dogs, and 0 of 503 control dogs of other breeds.

Considerations for Breeding

The frequency of SDCA1 and SDCA2 mutations in Belgian Shepherds is currently unknown. As more dogs are tested, it is likely that we will soon have better information about this.

The pattern of inheritance of both types of SDCA is known to be classical autosomal recessive, which requires that individuals inherit 2 copies of the mutation, 1 from each parent, to be affected⁶. All affected individuals are homozygous and will die young, normally between 2 and 4 months. Since both identified forms of the condition are lethal, there are no living dogs who are homozygous for either form of SDCA. However, we cannot be certain that all forms of ataxia will be the same in this regard. The modified Punnett Square diagram below illustrates the autosomal recessive inheritance pattern and what that means for both known forms of SDCA – SDCA1 and SDCA2. Affected puppies will die, or be euthanized, sometime between 2 and 4 months.

Modified Punnett Square for SDCA1 and SDCA2

	Normal Male	Carrier Male	Affected Male (dead)
Normal Female	100% Normal Puppies	50% Normal Puppies 50% Carrier Puppies	N/A
Carrier Female	50% Normal Puppies 50% Carrier Puppies	25% Normal Puppies 50% Carrier Puppies 25% Dead Puppies	N/A
Affected Female (dead)	N/A	N/A	N/A

While ataxia was originally found in dogs of working line descent, it has also been identified in show dogs with both working and show bloodlines in their pedigrees. It is possible that an intelligent approach to breeding could reduce the frequency of SDCA1 and/or SDCA2 in the breed. However, this should not be done at the expense of genetic diversity. It is important to balance the health of the breed with the health of the individuals.

The Belgian Shepherd Health Project considers the following items relevant to breeding decisions:

GOAL: Reduce the frequency of SDCA1 and SDCA2 mutations in the gene pool of Belgian Shepherds without adversely impacting genetic diversity. It may even be possible to eliminate SDCA1 and/or SDCA2 entirely with a measured approach.
All breeding dogs should be tested for both SDCA1 and SDCA2 before breeding.
Great care should be taken to avoid breeding carriers to each other, because 25% of the offspring will die, and two thirds of the surviving puppies will be carriers.
Exceptional dogs that are carriers should be evaluated carefully before breeding, with all the usual caveats associated with identifying dogs that are appropriate for breeding – the dog should be in excellent health, should be of excellent temperament and character, and should be of appropriate type for the breed. Individual breeders will have their own definition of exceptional based on the activities in which they participate, but it is likely that any such definition would also include an allowance for dogs with unusual or rare pedigrees.
- Example #1: A breeding of dogs that combines bloodlines that are not commonly found in modern pedigrees:
  - It would be in the best interest of the breed to consider breeding a daughter that is also a carrier.
  - It would be in the best interest of the breed to consider breeding a son that is also a carrier. However, the number of breedings of a male carrier should be limited.
- Example #2: A breeding of a popular stud dog to a female from bloodlines that are not commonly found in modern pedigrees:
  - It could be in the best interest of the breed to consider breeding a daughter that is also a carrier, though this is less beneficial than for a female from entirely novel bloodlines.
  - It is less likely that it would be in the best interest of the breed to consider breeding a son that is also a carrier, though if the number of breedings is limited, the impact would be similar to that of a daughter and might be acceptable.
- Example #3: A breeding of a popular stud dog to a female from bloodlines that are commonly found in modern pedigrees:
  - It is probably not in the best interest of the breed to consider breeding carrier offspring who have numerous siblings or half-siblings of popular bloodlines that are not carriers.
If there is a suitable alternative, carriers should not be bred, as 50% of their offspring will be carriers. Over time, this would result in an increased frequency of the mutation in the breed if their carrier offspring are also used in breeding. However, if testing of all the offspring is done and efforts are made to minimize the number of carrier offspring that will be used for future breeding, the impact of choosing to breed a carrier can be minimized.
Males have the potential to impact the breed more than females due simply to the number of offspring they might produce. This is frequently referred to as the “Popular Sire Effect”. However, a breeder might choose to use a carrier male for a very limited number of breedings, thereby minimizing the impact of the male on the overall frequency of the mutation while still ensuring the contribution of his genetics to the gene pool. In general, limiting the number of breedings for males is also a preferred strategy for promoting genetic diversity within any breed⁷.

Though knowledge of both SDCA1 and SDCA2 is becoming more widespread among breeders of Belgians, it is not commonly known outside of the breed. So, it might be wise to inform your veterinarian of the status of your dog, particularly if you decide to breed him or her. And, if you end up with a litter of puppies that appear to suffer from any form of ataxia, be prepared to educate your veterinarian about the condition. In that situation, it might be wise to print out some of the primary literature referenced in this article to give to your veterinarian.

Leading Academic Resource

If you believe that you have a litter with ataxia, the best thing to do is to test all the puppies as soon as possible, particularly if the parents have not been tested. If you already know that there is no possibility that the puppies are affected by either SDCA1 or SDCA2, meaning that at least 1 parent is not a carrier for each mutation, we encourage you to contact the Institute of Genetics at the University of Bern, where both SDCA1 and SDCA2 were identified. They can give you detailed instructions on how to proceed if you wish to help advance the scientific research into currently unidentified forms of ataxia. The director of the Institute of Genetics is Professor Dr. Tosso Leeb. His email address is: tosso.leeb@vetsuisse.unibe.ch

Belgian Shepherd Health Project Involvement

We are very lucky to have genetic tests available to help us detect both SDCA1 and SDCA2. However, little else is known about either condition. While it is reassuring that we have not heard of any health issues commonly found in carriers, an absence of evidence is not the same as evidence of absence. Given the unexpected complexity of ataxia, multiple genetic causes, and the timeline over which all of this has been discovered, we believe it is important for both breeders and owners to fully understand whatever the true implications of SDCA1 and SDCA2 in heterozygous carriers might be. It is important to know whether those dogs experience the same good health as the general Belgian Shepherd population, or if either SDCA1 or SDCA2 carriers experience certain health issues more often than other Belgian Shepherds.

We propose to follow dogs that have been identified as carriers over the course of their lives using annual (or semi-annual) surveys to evaluate their overall health and compare their results to Belgian Shepherds with similar pedigrees that do not carry SDCA1 or SDCA2. As for all studies of these types, we begin with a working hypothesis, called the null hypothesis:

Null Hypothesis: There is no difference in the risk of health issues between Belgian Shepherds that are carriers of SDCA1 or SDCA2, and those that are not.

The null hypothesis is the natural starting point for an investigation into any condition. It assumes that there are no significant differences between the groups. That’s how we’ll begin our project, with the assumption that there are no significant differences between normal dogs and dogs that are carriers for either SDCA1 or SDCA2. We’ll look at overall health, comparing the SDCA1 or SDCA2 carriers to normal dogs of similar ages and bloodlines. As long as there is no evidence to the contrary, we would conclude that carriers of either SDCA1 or SDCA2 are equally healthy to normal Belgian Shepherds.

Closing Remarks

There are a few things that we would like to emphasize in closing. If you are surprised to find that you own a carrier of either SDCA1 or SDCA2 following testing, there is no reason to panic. There is no evidence that suggests that these dogs suffer from any ill effects as a result of being carriers for either SDCA1 or SDCA2. It may impact your breeding decisions, but it is unlikely to impact the life of your dog.

Finally, we want to reiterate that these conditions are not well known or recognized outside of the breed. If you find yourself in need of veterinary assistance as a result of what you believe to be ataxia, we encourage you to be prepared to provide basic information about the condition to your veterinarian. Alternatively, contact Dr. Tosso Leeb at the Institute of Genetics, University of Bern.

We hope that you have found this article to be useful. We anticipate providing updates as additional information becomes available.

Glossary

Ataxia/ataxia: Is a disease of the nervous system that results in cerebellar degeneration and death in Belgian Shepherds. Symptoms typically begin at around 4 – 6 weeks of age and include a progressive loss of coordination.

Autosomal recessive/autosomal recessive: One way in which genetic traits can be passed from parents to offspring. Traits inherited in an autosomal recessive manner require that the offspring receive a copy of the defective gene from both parents to develop the condition.

Heterozygous/Heterozygote/heterozygous/heterozygous: A dog (or any animal) that has copies of 2 different forms of a particular gene, having inherited a different form from each parent.

Homozygous/Homozygote/homozygous/homozygote: A dog (or any animal) that has 2 copies of an identical form of a particular gene, having inherited the same form from each parent.

Mutation/mutation: A permanent alteration of the DNA sequence that makes up a gene, such that the sequence differs from what is found in most individuals.

Null Hypothesis/null hypothesis: The null hypothesis is a statistical concept that presumes there is no difference between groups. It is frequently used as a starting point to begin gathering evidence to either prove or disprove that the groups are identical with respect to the attributes being studied.

Punnett Square/Punnett square: A tool used in genetics to predict the outcome of a particular breeding. It traditionally uses genotype but can be modified to show phenotype.

Volker Riedel: An influential German breeder and judge, with particular focus on modern, working line Malinois and IPO in the German DMC club.

Referenced Sources

1. Riedel, V., 2013. Ataxie beim belg. Schäferhund, eine alte Geschichte, DMC article 26.04.2013 http://www.mechelaar.de/verein/news-detail/article/ataxie-beim-belg-schaeferhund-eine-alte-geschichte/

2. SDCA1-affected puppy videos from Marieke Wollschläger

3. Marieke Wollschläger Litter “C” Website http://www.malinois-unter-schwarzer-flagge.de/html/c-wurf.html

4. Mauri, N., Kleither, M., Leschnik, M., Högler, S., Dietschi, E., Wiedmer, M., Dietrich, J., Henke, D., Steffen, F., Schuller, S., Gurtner, C., Stokar-Regenscheit, N., O’Toole, D., Bilzer, T., Herden, C., Oevermann, A., Jagannathan, V., and Leeb, T. A Missense Variant in KCNJ10 in Belgian Shepherd Dogs Affect by Spongy Degeneration with Cerebellar Ataxia (SDCA1). G3: Genes, Genomes, Genetics 2017 Feb 9;7(2):663-669. Doi: 10.1534/g3.116.038455. http://www.g3journal.org/content/7/2/663

5. Mauri, N., Kleither, M., Dietschi, E., Leschnik, M., Högler, S., Wiedmer, M., Dietrich, J., Henke, D., Steffen, F., Schuller, S., Gurtner, C., Stokar-Regenscheit, N., O’Toole, D., Bilzer, T., Herden, C., Oevermann, A., Jagannathan, V., and Leeb, T. A SINE Insertion in ATP1B2 in Belgian Shepherd Dogs Affect by Spongy Degeneration with Cerebellar Ataxia (SDCA2). G3: Genes, Genomes, Genetics 2017 Aug 1;7(8):2729-2737. Doi: 10.1534/g3.117.043018. http://www.g3journal.org/content/7/8/2729

6. Kleiter, M., Högler, S., Kneissl, S., Url, A., and Leschnik, M. Spongy degeneration with cerebellar ataxia in Malinois puppies: a hereditary autosomal recessive disorder? J Vet Intern Med. 2011 May-Jun;25(3):490-6. doi: 10.1111/j.1939-1676.2011.0720.x. https://onlinelibrary.wiley.com/doi/full/10.1111/j.1939-1676.2011.0720.x

7. Beuchat, C. The Pox of Popular Sires. Blogsite: The Institute of Canine Biology 2013 Dec. 5 https://www.instituteofcaninebiology.org/blog/the-pox-of-popular-sires

Additional Resources

1. Avonwolf Malinois Website, story of SDCA2 puppy: https://avonwolf.co.uk/litters/d-litter/

2. Cachin, M and Vandevelde, M Congenital Tremor with Spongy Degeneration of the Central Nervous System in Two Puppies. J Vet Intern Med. 1991; 5:87-90. http://www.malinois-unter-schwarzer-flagge.de/spongydegenerationJVIM1991.pdf

3. Institute of Genetics, University of Bern: http://www.genetics.unibe.ch/research/documents_dogs/cerebellar_ataxia_in_the_belgian_shepherd/index_eng.html

4. KCHBO List of Tested Dogs: http://www.kchbo.com/soubory/veterina/SDCA1_list.pdf

5. Finnish List of Tested Dogs: https://kayttobelgi.info/ataksia.php

6. List of laboratories that are currently capable of testing for both SDCA1 and SDCA2, to the best of our knowledge:

a. Animalabs
b. Embark
c. Genomia
d. Laboklin
e. Vetgen

The views and opinions expressed in this educational/informational media product, including articles, analyses, and slide shows, are the informed opinion of the author(s) and do not necessarily reflect the official policy or opinion of their employer(s), or any other organization, agency, or company. Assumptions made in any data analysis are not reflective of any position other than the author(s). Please keep in mind the constant availability of new data means that views and opinions are always subject to change, revision or rethinking.