We ear about a terrible disease, ten pups were affected in North America. The name in the breeder circle is Bandera's syndrom named neonatal ataxia by the veterinary doctors. Dr O'Brien from Missouri university, studies this disease and honnor us Cotons fanciers with his article.

If we choosed to publish it this month it isn't to afraid people who read us but overall to help the doctors who try to understand and find solutions to this disease. You can if you have any information (they will kept them strictly confidential) contact them. Adresses are at the end of the article.

You can too visit the website http://www.cvm.missouri.edu/ataxia/. Clicking on the picture you'll be able to watch at a video, take care, it's very hard to see.

Neonatal ataxia in Coton de Tulear dogs.

Signs of neonatal ataxia.     Ataxia refers to a lack of normal coordination of movements. Neonatal refers to the period of time immediately after birth. Thus the term neonatal ataxia means a lack of normal coordination which becomes evident soon after birth. In the breeder circles, the condition is called Bandera’s syndrome after the second puppy identified with the disease.     All affected pups showed similar clinical signs. They nursed well and grew adequately, but had difficulties from the time they become active enough to be able to clearly identify motor problems.Affected dogs are unable to stand and walk and might be generically referred to as ‘swimmers’. They move all four limbs, sometimes with good strength, but are unable to stand and walk.

Affected pups are unable to walk and fall sideto- side when attempting to move.

When attempting to move, they will frequently push themselves forward, but inevitable fall to one side or the other
where they may continue to paddle in an attempt to get up again. Another common sign is a tremor or bobbing of the head. This head tremor is most dramatic when the pup is trying hardest to hold the head steady as when they are trying to eat or sniff an object and is referred to as an intention tremor. There may also be a tremor or jerking of the eyes.
    There does not appear to be any real progression or improvement in the condition. Some pups seemed to adapt to their disability to some extent and function better, but they never gained the ability to walk. Other than the motor difficulties, affected pups appear to develop normally. The are bright and aware of their surroundings and learn quickly. Their appetite is good and they grow well as long as they can get to their food.
    Several pups which were euthanized had post-mortem exams performed. Thus far, no clear changes in the areas of the brain responsible for coordination have been found. This suggests that the problem is at the biochemical rather than the structural level. Extensive screening tests for biochemical abnormalities which might affect the brain have also yielded no clues thus far. Currently researchers who specialize in the anatomy of these coordination centers and the types of biochemical abnormalities which might affect them are continuing to look for clues to the underlying deficit in these dogs.

What other diseases might look similar?
As mentioned above, the affected pups would look like the generic class of ‘swimmer pups’. Most typical swimmer pups suffer from a combination of overnutrition and poor footing when they are developing. The obese pups simply don’t have the strength to keep their legs under them on a slick surface such as linoleum and laying on their stomachs all day long leads to malformation. Most of these classic swimmer pups improve well with diet and an improvement in the surface they have to walk on.
    The hereditary cerebellar ataxia (abiotrophies) cause similar (though usually not as severe) clinical signs. These diseases are characterized by a period of normal development followed by progressive loss of coordination. The Cotons with neonatal ataxia are affected from birth. Also, specific cells in the cerebellum (the main coordination center of the brain) are lost in the cerebellar ataxias whereas no cell loss has been identified in the Cotons.
    Most other congenital diseases affecting the brain such as hydrocephalus (water on the brain), liver shunts, or infections affect more than just coordination and affected dogs are dull, slow to learn, or show other signs such as seizures.

What evidence is there that this is a hereditary disease?     When presented with a single dog affected with a neurologic disease, the veterinarian must consider all the myriad of disease processes which can cause brain damage and the type of signs seen. When no clear cause is found, we consider a hereditary condition, but it isn’t until multiple affected dogs are identified that we can begin to answer the question of whether or not a condition is hereditary.

Neonatal ataxia fits an autosomal recessive mode of inheritance. Both males (squares) and females (circles) are affected (shaded symbols). Parents are normal but carry the defective gene.

    Hereditary disease can either be autosomal dominant, autosomal recessive or sex linked. In sex linked disease, only one sex (usually males) is routinely affected. In autosomal dominant disease, one parent is affected and an average of 50% of the offspring are affected. Most hereditary diseases in dogs are autosomal recessive. In autosomal recessive disease, both parents are carriers of the disease. They usually show no signs of the disease themselves, but an average of 25% of the offspring are affected with the condition when two carriers are mated.
    What is the evidence that neonatal ataxia is hereditary in the Coton de Tulears? First, extensive testing has failed to identify another cause for the disease. This included looking for liver shunts, toxin exposure, infectious diseases and dietary problems. Most environmental or infectious diseases do not affect only a small percentage of the litter. All the pups are in the same environment and exposed to the same chemicals or infectious agents, and thus are almost
equally likely to have problems.
    Ten affected pups from seven different breedings have been reported thus far. There were a total of 34 pups in those litters. This is very close to the 25% rate expected when dealing with an autosomal recessive trait. Also all the parents were normal as expected with a recessive condition, and males and females were equally affected. Thus all the evidence suggests we are dealing with an autosomal recessive disease.

    The next question is how extensive is the problem in the population. There are formulas for calculating gene frequencies in populations, but more data than is currently available would be necessary to do such calculations. We can estimate prevalence by looking at how many generations back we need to go to find a common ancestor in all affected dogs. If all affected dogs had a common ancestor on both sides of the pedigree only a few generations ago, then the mutation which causes the disease may have originated with that individual and not be very widely distributed. Unfortunately, going back multiple generations in the affected dogs, we cannot find a sole common ancestor to all affected dogs. This suggests that the mutation may be more widespread in the breed than originally thought. This is not uncommon with recessive traits where the disease can lay dormant for generations before popping up again when the right combination of parents occur.

Do we eliminate the carriers from the breeding population?
    When dealing with a common breed, such as Labrador Retrievers or German Shepherds, there is a large enough gene pool that carriers of a genetic disease could be eliminated from the breeding stock without diminishing the overall genetic diversity of the breed. When dealing with a relatively small breed such as the Coton de Tulears, this may not be the best strategy for the breed. If the gene is indeed widespread in the breed, many dogs would have to be eliminated from the breeding stock. This could create a serious bottleneck in the breed and decrease desirable genetic diversity. This can lead to an increase in other, unrelated genetic problems down the road as there are fewer lines to choose from when making breeding choices. It would be simply trading the devil you know for the devil you don’t. An alternative strategy is to continue to use carriers but ensure that two carriers are never knowingly bred together. This allows the desirable characteristics of the carrier (including the genetic diversity necessary for the future of the breed) to be maintained, while avoiding producing affected pups (breeding two carriers is necessary to produce affected pups). Any time a carrier is bred, 50% of the offspring will also be carriers. Without a DNA test for the condition, there is no way of knowing who is a
carrier other than by trial breeding. Thus a small percentage of affected pups is the price that will need to be paid to continue using carriers in the breeding program. The advantage is that the desirable traits of the carriers are not thrown out with the bath water. This approach requires honesty and courage on the part of the breed clubs to admit who has produced affected pups, and not shun those dogs that have if they have other characteristics desirable to the breed. One advantage of the neonatal ataxia over some other genetic diseases such as the abiotrophies or hip dysplasia, is that affected dogs can be clearly identified before they would be sold to a new owner.

What else might be done?
    The obvious answer to the whole problem is to develop a DNA test for the mutation responsible for the disease. Advances in the canine genome project have made this more of an attainable goal than it was even a few years ago, but there are still few of these tests readily available. In most dog diseases where gene testing is available, we have had a clear clue that tells us what human disease the canine disease is similar to. Then we can use the knowledge gained from the human genome project to look at whether the same gene is responsible for the canine disease. A good example of this is muscular dystrophy where affected dogs had changes in the muscle identical to those seen in affected children. It was then found that the same gene was responsible for the problem in Golden Retrievers and humans. This (and the fact that there is a large gene pool in the Golden Retrievers) made it easy to deal with that problem. We are still a ways from being able to take a disease such as neonatal ataxia where we have few clues to the underlying gene responsible, and find a marker to aid us in clearing the gene responsible from the breed. That day is coming, but meanwhile what is necessary is further study of affected dogs to gain clues to the cause and gathering the pedigree information and DNA samples that will allow us to track the gene when those tools become available to us.

How can you help?
    If you have a litter with a pup you believe might be affected, please contact one of us. We can help you in determining whether or not this is the problem in your pup. We will also ask for pedigree information and DNA samples for future use in tracking the gene responsible. Any information provided to us will be kept strictly confidential.

For further information, visit http://www.cvm.missouri.edu