Chinese Beagle Syndrome Revisited
(Article Published in the March 2005 Show Beagle Quarterly) -reprinted with permission

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A CASE STUDY

First, the dam of the litter, which produced this puppy, had whelped 2 large litters prior to this one.   Sires were different for all 3 breedings.   All of the animals in question (dam and 3 sires) are the products of the traditional show foundation stock present in virtually all of our pedigrees.   A huge majority of the ancestors are finished show champions in all the relevant pedigrees.   The dam has 2 litter sisters (also finished), which were used for breeding multiple litters from various sires.   The sire has been used a good bit.   This CBS puppy is the only one produced by the dam out of 22 puppies, and as far as can be determined, the only one produced by the sire out of many more puppies.   The dam did produce one puppy in a previous litter which, in hindsight, has some characteristics of dwarfism – not severe, and in fact the puppy was shown a bit and pointed, although not finished – but there were a short neck and legs for the rest of the dog, and a tendency of feet to turn out.

The current CBS puppy was the smallest in the litter, and was “different” from about the time they started to walk.   Her head and eyes were different than the other puppies’ and when she walked she had a sort of rolling gait in the back, and a tendency to hop rather than run.   However, nothing about her was so alarming as to raise grave concerns except a heart murmur.   That was no longer heard at 8 weeks and she was placed in a pet home that had been waiting for her for a long time.   By the time she was about 11 weeks old, her legs were much stiffer and she was decidedly up on her toes.   At this writing she is 6  months old and is badly misshapen both front and rear (see pictures).   She is unable to flex normally in the rear to sit, just as described in the Musladin/Leuke article.    But progression of the condition seems to have stopped – she has not gotten any worse in the last 30 days.    She does not evidence any pain at all, plays, eats well, and is very smart and responsive.   Her people adore her and declined a replacement.  She does not have much lung capacity and gets winded easily but otherwise appears fine.   Hopefully she will live a long and otherwise healthy life.

One of the litter sisters appears to possibly be very mildly affected.   Her legs and movement are fine, skull not overly wide, but her eyes are a bit slanted and she has odd cartilage her ears – as does the affected puppy and, it is now realized, the dam.   Her outer toes are not the classic high toes, but her feet are not as good as the other siblings.    This was the pick puppy as the baby, and were it not for the badly affected puppy, these very slight indications of CBS would surely never have been noticed.   As it is, the dam has been spayed and this puppy will be spayed and placed because of the suspicion of mild affectation.   The badly affected puppy, of course, will also be spayed.

The other puppies are phenotypically perfect ... in fact of quite consistent quality.

This litter has caused some reflection on whether the removal of animals from the breeding population should extend beyond the parents and clearly affected offspring.   Is it even necessary to remove the parents?  Musladin/Leuke recommend not repeating the breeding, obviously.   There is no DNA test, and the condition is not common enough to warrant the expense of identification of the gene(s) at least to this point.    Why is the condition so rare?   The gene pool of show-bred Beagles in the U.S. isn’t that large.    Why is the condition fatal in other breeds, but not in Beagles?

Discussion with several vets, some longtime breeders with an interest in the syndrome and other people of science suggests some new ideas on the matter.   These are offered as food for thought, not as facts founded in scientific research.
First, one school of thought suggests that perhaps this is more akin to juvenile spinal muscular atrophy (SMA), a deficiency of a motor neuron protein causing loss of nerve cells in the spinal cord, or to myleodysplasia, which refers to a number of malformations of the spinal cord that occur as a result of abnormal pre-natal development of the neural tube (which becomes the spinal column), than to the cerebellar abiotrophy (inherited degenerative disease of the brain) which is fatal in other breeds.  That would explain the heretofore mysterious circumstance that Beagles stabilize eventually while other breeds perish.   BUT, these conditions cause weakness in addition to the characteristic bunny hopping, and SMA is progressive.   In this latest puppy, and in the others we have been able to find, there is no particular weakness, and the condition is not progressive.  They stabilize at about 6 months and get no worse unless some other condition occurs.  They are lively, smart, trainable and particularly lovable.   One still living which is now 14 years old did get glaucoma at about age 9, probably due to his very small eye sockets.   His eyes had to be removed but he has been happy and healthy, though blind, ever since.
One conclusion those now looking at the condition seem to concur on is that this is not a neuronal or cerebellar abiotrophy.   It is more likely some combination of a nervous system/musculoskeletal system disorder.   One opinion is that this is a rare form of or a severe manifestation of the chondrodystrophy or chondrodysplasia known as skeletal dwarfism.   Support for this theory is the known occurrence of both dwarf puppies and Chinese Beagle Puppies in the same litter.    The CBS is much rarer, of course.   Signs of dwarfism are seen quite frequently, including in the show ring:  short toes, bowed legs, turned out feet, short necks and legs, shortened spine and/or ribcage, etc.      Cases don’t have to be severe to signify an affected animal, and in genetic terms, that means both parents carried the recessive gene to produce the condition.

Given the rarity of Chinese Beagle Syndrome puppies, is it possible that rather than being a simple recessive (each parent supplying one recessive gene, with the expected result of 25% affected, 50% carrier, 25% clear), could it be multi-genetic?   Is it possible that both parents must have more than one specific recessive gene?   Is that why a dam and sire which have been bred multiple times never produce an affected puppy until the unlucky breeding where they meet one of the few other Beagles in the breeding pool which is a carrier of both or all of the required genes to produce a badly affected puppy?    Could the occasional Beagle with eyes more slanted than expected, or with high toes, or an earset affected by odd cartilage in the ears be the product of parents wherein one carries both/all the genes, but the other does not.   Or wherein both parents carry one or some of the genes?      These minor imperfections are unnoticed or ignored because the rest of the animal is of high quality.    If this theory has credence, it follows that it requires fairly incredible bad luck to find two Beagles which both are carriers of the entire genetic string required to produce a badly affected puppy.   If CBS is multi-genetic perhaps most of our Beagles carry some part of the recessive gene code, a few carry all of it  (CBS beagles) and some carry most of it  (carriers with no symptoms).   It only appears in full force when they are bred to another carrier of all of the recessives.    And then, while some of those puppies may be fully affected, others may be mildly affected, while the rest will either be carriers or clear.    If there is indeed a relationship in this genetic code to chondrodystrophy, the possibilities become even more intriguing.   Do the simple recessives produce the dwarfism, while the same plus more recessives are required for the CBS.   If true, this would mean that any animal which produced a CBS puppy is de facto a carrier for dwarfism.   There is a school of thought that says all Beagles are carriers for chondrodystrophy, as are Bassetts and Doxies – that is how the smaller hounds were developed, by breeding for smaller skeletal structure (but not, of course, for the bowed legs and turned out feet of the Bassett Hound, or the extreme shortness of leg of the Doxie).

What is the rational and responsible thing to do with a breeding program faced with Chinese Beagle Syndrome?   Common sense would dictate that you certainly do not repeat the breeding, and if the animals continue to be bred they should not be bred to direct descendants or antecedents of the animal that produced the affected puppy.   One should probably assume that puppies which appear to be very mildly affected are still affected and as such do not qualify as candidates for the breeding pool.    On the other hand, a condition which had been reported in only 19 Beagles at the time of the Musladin/Leuke article, and about which not a single subsequent article or research paper has appeared in the last 12 years, certainly does not warrant decimating an entire breeding program.    What would you replace them with?    There is no way to know which animals are carrying the recessive genes, and what combination of genes may produce one of these very rare badly affected puppies, other than those which have already produced it.    It is not reasonable or even possible to breed away from something so elusive and hard to pin down.

Our conclusion then, is that when such a puppy is produced, subsequent breedings of the siblings and other closely related animals must be carefully undertaken.  Stay away from the pedigree which in combination with your own produced the affected puppy(s).   You know with absolute certainty that the dam and sire of that litter carry all of the recessive genetic code to produce Chinese Beagle Puppies.   You know that the affected puppy does as well.   You don’t really know anything else for certain.   Other puppies may be perfectly clear of any of the recessives.   Siblings of these parents may be carriers or may be clear.     Once CBS is identified in a line, it is probably also prudent to carefully observe all puppies produced by these animals for these small differences, which may indicate that the recessive gene(s) has cropped up and is present in one or more puppies.   By the time the litter is 8 weeks old, those differences can be seen if you are looking for them.     A puppy showing symptoms, even if minor, can probably be assumed to be “affected” in genetic terms and should probably not be bred.   If feasible, a dog or bitch known to be a carrier can actually rule out other related animals through test breedings.   This is a difficult undertaking, emotionally and financial, and not realistic for most.

As the result of the research undertaken following the identification of this CBS puppy, we have made contact with 3 veterinary schools and 2 of them wish to see a video of the puppy and potentially do a little research.   As noted above, she is a beloved and doted upon pet, so nothing invasive will be permitted.   But if anything comes of this, we will certainly share it on a follow-up basis.    We have learned that UC-Davis is willing to collect DNA and store it for free, and that any research into this would require that at least 100 DNA samples of Beagles be on file, just as a starting requirement.   We know of several breeders who have submitted samples, and encourage more to do the same.   The DNA of the affected puppy in this article, her dam and siblings, and all the rest of the breeding stock in her home are being submitted, with the affected and known carrier identified.    If you have ever produced puppies which either demonstrated dwarfism or Chinese Beagle Syndrome, you can help the breed by doing the same, without any public identification of yourself or your dogs.

The link is http://www.vgl.ucdavis.edu/requestform/

It is somewhat astounding that the Canine Inherited Disorders Database does not list the Beagle as a breed which experiences osteochondrodysplasia (a/k/a chondrodystrophy) since it certainly does.    One of the people consulted during this research is going to let them know about that and pass along what is known.   We learned that Dr. Mark W. Neff of UC Davis was reseaching this using intramural funds. That was a long time ago, and starting all over may be a heavy order at this point, but we are going to see what it would take.

Again, this is all anecdotal data, and certainly not based in true scientific research.   But if it gets these devastating conditions in front of the fancy and generates any excitement about working to eliminate them, it is well worth the effort and the ink.    If the genetic markers could be identified, a simple DNA test could tell us which animals were carriers and which were clears.    Clears bred to clears produce only clears.    Even carriers bred to clears produce half and half.   Carriers bred to carriers will even produce, statistically, 25% clear puppies.   If we had the research and the test, these problems could be ELIMINATED from the breed in just a few generations, if all responsible breeders did the testing, disclosed the results and bred judiciously.