Cerebellar Cortical Abiotrophy:


Cerebellar Cortical Abiotrophy (CCA) is a condition caused by a single cell simple autosomal recessive gene found only in Gordon Setters (and possibly Kerry Blue Terriers.)  I have owned a CCA-affected bitch, who was whelped in 1976, so I am personally well acquainted with the condition.  This was a bitch I purchased, from a kennel that may as well remain nameless; suffice to say that she was never bred, and nothing from her bloodlines is in any of Bright Starís current breeding and non-breeding stock.


My CCA-affected bitch competed in field trials as a puppy and derby and earned several placements.  She also finished as a show champion.  At the age of 3 1/2 years I first noticed some suspicious movement on her part in the show ring that led me to suspect CCA; I had seen a few Gordons previously who were affected.  A visit to my vet, who had worked with several of these dogs, dating from before the condition was identified and researched, confirmed my suspicions.  At that time this bitch already had about 10 points with a major, and I chose to go on to finish her championship even though I knew I would not breed her.  At this time, the genetics of the condition were only suspected, but I didn't want to take a chance.  Over the years, her condition deteriorated in plateaus, but she was never unable to accompany us camping in the mountains or otherwise in need of curtailed activity.  She lived to be 11 1/2 and died from a heart valve defect, completely unrelated in any way to the CCA.


The first CCA-affected dog that I saw was in Petaluma in 1972.  At that time the condition was unknown, unstudied, and undocumented.  The local vets thought that it might be a form of encephalitis.  A Dr. Melick, a military veterinary pathologist stationed at the Presidio in San Francisco, did some preliminary work on samples taken from this affected dog, and his work became known to a Dr. De La Hunta, one of the teaching staff of Cornell University's School of Vet Med.  At that time, Dr. De La Hunta was on a one-year visiting professor program at the University of California at Davis school of Veterinary Medicine.


Dr. De La Hunta had a graduate student back at Cornell named Jerold Bell, who happened to own a Gordon Setter male that suffered from a similar set of symptoms as the Gordon studied in California.  As a result of the work done in San Francisco and his association with Jerry Bell's dog, De La Hunta began a research project on the nature of the condition while at UC Davis and completed it at Cornell.  His study determined exactly what was going on in the brains of affected dogs, and the results were published in the Journal of Veterinary Medicine around 1981.  I believe that the condition was also given its now-official name in this article: cerebellar cortical abiotrophy.  Prior to this time the different vets working with affected Gordons variously called it cerebellar ataxia, cerebellar hyperplasia, and a variety of other medically descriptive terms.


The cerebellum is the part of the brain that governs balance, harmony, and coordination among all the parts of the body.  Symptoms of CCA include lifting the front and/or rear legs too high when gaiting, stumbling, difficulty with stairs, head tremors, general excessive clumsiness, falling, seeming loss of depth perception, and an inability to stand up.  Not all affected dogs necessarily have all of these symptoms, and other symptoms may also be present.  Some affected dogs progress very rapidly and are incapable of standing by one year of age; others have less severe symptoms and a slower rate of progression, as my dog described above.


Dr. De La Hunta's article can easily be located and read in its entirety, if you wish.  The gist of it states that this is a condition unique to the Gordon Setter breed, although similar to one occurring in Kerry Blue Terriers.  The cerebellum is normal at birth, and at some time after birth begins to deteriorate, i.e., the Purkinje cells in the cerebellum were found to be blackened and dysfunctional in affected dogs.  The condition is progressive and degenerative; it cannot be reversed or controlled by medication, activity, diet, or surgical procedure; absolute diagnosis is possible only by post-mortem examination of the cerebellum; there are no other physical differences detectable in either affected dogs or in carriers; therefore there is no way to identify a dog as a carrier.  Probable diagnosis is by observation of neurological function; only Board Certified veterinary neurologists are deemed capable of positive determination upon observation, and even they often aren't certain, since similar neurological symptoms may be associated with many other conditions.


While Dr. De La Hunta was doing his studies at Cornell, a woman named Linda Cork was working on her PhD in Veterinary Medicine at Johns Hopkins University.  She had established a breeding colony of CCA-affected Gordons and was trying to determine if the condition was genetic, and if so, what was its mode of inheritance.  I think she also was looking into developing some sort of blood test to identify carriers, but that proved to be a dead end at that time.


I spoke with Dr. Cork by telephone in 1984 and she described the behaviors manifested by her colony of affected Gordons.  In several instances, the behaviors exhibited by my "affected" bitch were directly opposite, and she seemed able to function better under circumstances that Dr. Cork said induced a worsening of symptoms in her Gordons, and vice versa.  When I remarked on these particulars to Dr. Cork her response was to say that the condition might have various manifestations, but she was certain that it was all part of the same overall package.


I also offered to make my affected bitch available to Dr. Cork for use in a test breeding program: while I would not give her the bitch, whom I loved, I was willing to breed her to whomever the experts suggested, and surrender the entire litter of pups for research purposes.  Dr. Cork did not react favorably to my offer, and in fact only took my name and address with reluctance.  Needless to say, I never heard from her.


Shortly thereafter Dr. Cork published the results of her studies, claiming to have determined that CCA is a simple autosomal single cell recessive genetic condition.  She included diagrams showing what percentage of affected, carriers, and clears would statistically result from breedings of affected to affected, affected to carrier, carrier to carrier, affected to clear, and carrier to clear.


She postulated these results:  all pups resulting from the mating of two affected parents would be affected.  All pups resulting from the mating of an affected to a clear would be carriers.  Affected to carrier results in 50% affected, 50% carriers.  Carrier to carrier results in 25% affected, 50% carriers, 25% clear.  Carrier to clear results in 50% carrier, 50% clear.  I do not know how many affected dogs were in her breeding colony, how many litters she produced, how many generations were studied, nor where her results were published; they should be able to be located through Johns Hopkins University.


When Dr. De La Hunta's student, Jerold Bell, completed his DVM and went into private practice, he began compiling pedigrees of affected Gordons nationwide.  Using the above figures of Linda Cork, he began analyzing pedigrees of individual Gordons and prospective Gordon litters for the % probability of that dog or pups from that litter being either affected or carriers.  He still provides this service, for a fee and upon receiving written releases from owners of the Gordons in question, and may be contacted at Veterinary Genetic Consulting, P.O.Box 127, Enfield, CT 06082; (203) 741-0548.


For a while it seemed that the book was closed on CCA.  A couple of East Coast breeders were so disturbed by the evidence and publication of the genetic nature of the condition, that they stopped breeding entirely.  A mood of hysteria was generated nationwide, although more frenzied in the East, and rumors, denials, finger-pointing and witchhunts were the result.


The Gordon Setter Club of America established a genetics committee, specifically to look into coordinating information about CCA-affected Gordons with the goal of establishing a test breeding program nationally.  The only way to determine if a dog is a carrier or not, is to breed him to an affected member of the opposite sex.  If there are at least 10 pups in the litter, and none show any clinical signs of CCA by the age of two years, the non-affected parent may be presumed statistically proven a non-carrier.  The committee was headed by Judi Levy of Pennsylvania.  Judi ran into a lot of conflict and hostility from breeders and owners of affected Gordons, some of which stemmed from Jerry Bellís information-gathering process re affected dogs.


Judi enlisted the aid of Betty Cott of Ames, Iowa, a longtime Gordon breeder with a professional background in research and statistics.  Betty compiled a great deal of data re pedigrees of affected Gordons.  Her aim was to confirm the results that Linda Cork obtained from her breeding colony at Johns Hopkins, by showing occurrences of CCA throughout bloodlines using Cork's heritability figures.  In the interest of pure science, and so as not to implicate any particular breeders or bloodlines, she coded her data, so that no one could know who the particular dogs were in this research.


Judi Levy had Betty Cott present some preliminary results of her study at a GSCA General Membership meeting held in Ohio in the mid-1980ís.  From what Judi later told me, Betty was met with such hostility and accusations that Judi decided there was no further purpose for the genetics committee.  She resigned as chairman and the entire committee was disbanded, with the possibility left open for re-establishment at a later date.  It has since passed through a couple of other incarnations, and its present status is indeterminate.


I don't know if Betty Cott continued to pursue her research but both she and Judi Levy were quite willing to discuss the CCA issue if they were approached in good faith.  Both had rather hard feelings and other difficulties with the topic, although they were as knowledgeable about CCA as any Gordon fancier could be.  Both are now deceased and one wonders how much knowledge disappeared with their passing.


In recent years, the furor about CCA among Gordon breeders has calmed.  There are still new cases of CCA cropping up in all bloodlines.  Very few if any test matings have taken place, since few breeders have the facilities to care for ten or more pups until the age of two!  (This is vastly different from the situation with the Irish Setter Foundation and PRA [Progressive Retinal Atrophy], which you may be familiar with; that condition is diagnosable by 10 weeks of age, and there are many test-bred clear Irish Setters.  In 1995 through genetic mapping, the gene specifically responsible for causing PRA in Irish Setters was identified, and a blood test to identify carriers has recently been developed.)


Two other points regarding CCA need to be made: To the best of my knowledge, no one has attempted to establish another affected breeding colony and duplicate Linda Cork's results, thus verifying her determination of the genetic nature of this condition and the specifics of its inheritance.  As acquaintances of mine have proceeded through doctorate programs, I have become quite aware of the lack of preciseness in the procedures and results of much research, as well as the wide leeway that exists for interpretation of those results.  Furthermore, there are other pressures on the researcher that often lead him or her to a bit of haste, or a less than perfectly scrupulous presentation of results, or a rush to publish.  These can range from financial issues, to time deadlines, to inter-departmental and inter-disciplinary political pressures and concerns.  Thus the importance and value of duplicate studies.


Although I was less than impressed with her unwillingness to hear anything that differed from her concept of the condition, I don't mean to impugn Dr. Cork's research in any way.  I am stating that, to the best of my knowledge, her results have not been independently verified, which I believe is the basic criterion for acceptance of any scientific theory.


Secondly, there is a breeder in my area who prides himself both on the number of Gordon Setters that he produces each year, and the degree of intense inbreeding in his breeding program.  He has produced about 300 pups annually for some 20 years, and regularly breeds father/daughter, mother/son, and full siblings.  There is acknowledged CCA in his bloodlines, and in fact one of his two prime foundation studs was an acknowledged CCA carrier.


If Linda Cork's figures are accurate, this breeder should be producing a large number of CCA-affected dogs, and that number should increase regularly each year.  In fact, however, it seems that the incidence of CCA appearing in his dogs is no greater than that in the overall Gordon population, in which it seems to fluctuate with time, some years producing several affected cases in a number of litters and bloodlines, and other years producing none.


This has led to speculation that the condition's manifestation is more complex than previously thought, and breeders are now beginning to postulate an environmental trigger necessary to onset the condition in a genetically susceptible animal.  Such environmental triggers are a well-established fact in manifesting genetic potential in numerous conditions, both in animal and human medicine.


So it all makes me wonder!  And I seriously doubt that the bottom line has yet been discovered or written about CCA.  Stay tuned!