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The article below
was printed in The American Beagle- Spring 1979. Reprinted
with permission from author.
INTRODUCTION
Over the past few years there
has been a growing concern among beagle breeders over the
increased incidence of epilepsy in our breed. It is the
intent of this paper to describe the syndrome and its genetic
significance. There is a glossary of terms at the end to aid
the reader in understanding some of the concepts. A
bibliography was included, not because expect most readers to
wade through the scientific treatises, but because I wanted to
give credit for the material from which I drew so heavily. On
a few occasions I have given an opinion, and I hope clearly
stated that it was opinion only.
Although epilepsy has been
found in many, many breeds, those most often afflicted are:
all three varieties of poodles, Keeshonden, German shepherds,
Belgian shepherds, and Beagles.
Epilepsy is a dysfunction of
the brain which manifests itself with some type of seizure.
The seizures may vary from mild to extremely severe, in some
cases causing death.
Many terms have been used to
mean seizure, such as convulsion, fit, or epileptic attack.
These terms are used to describe the abnormal behavior that
occurs at any one time, whereas epilepsy is the term that
applies to the disease itself.
The very word “epilepsy” comes
from the Greek meaning “to be seized.” Martin Luther called it
the “demon disease.” The supernatural interpretation of
seizures is centuries-old, and over the centuries the casting
out of the responsible devils took many forums. In Christ’s
time, people spat on epileptics as a precaution against being
possessed themselves; from this custom arose the name “morbus
insputatus,” or “spitting disease.” In middle Ages, openings
were sawed in skulls of those suffering from unbearable
headaches or convulsive seizures to let the evil spirits
escape. Not until the eighteenth century did leading
physicians abandon belief in demon possession. In many parts
of the world, men still continue to treat seizures by
exorcism.
A convulsive seizure is the
physical evidence of an electrical storm within the brain.
This abnormal electrical activity is a phenomenon caused by
the physical and chemical makeup of the discharging nerve
cells in the brain. The overactivity of these cells produces
disturbances in consciousness and in muscular coordination.
Therefore the primary cause is chemical (or actually electro
physiochemical). But the chain of events leading up to the
brain’s chemical reaction can be infinitely varied. This
variety is what makes veterinarians so evasive about giving
pat answers.
One of the problems in
diagnosing a dog as to whether it has epilepsy or not is a
general lack of knowledge as to what a seizure is. I have
talked to several persons in dogs (all breeds) asking them if
they have observed seizures in their dogs. An all too frequent
answer is another question ... what does a seizure look like,
or how would I know if my dog was having a seizure?
Epilepsy varies so much as to
how it is manifested that only general terms can be used.
Epilepsy is not a specific disease, but rather a set of
symptoms which can result from many causes. There are three
main types of seizures, and if your dog has appeared to have
any of them, he is a strong suspect for epilepsy.
One of the less common forms
of epilepsies is called “petit mal” which is quite brief, and
only very subtle changes in behavior can he seen, such as
staring, falling, etc. It is possible that those seizures seem
to he less frequent because they would be harder to detect,
and therefore would not be reported. Although these seizures
do not seem to be as serious as others, their causes are
identical.
The second and roost common
type of seizure is what I call classical epilepsy. This
epilepsy has three phases. The first phase may or may not be
seen and immediately precedes the actual seizure. This phase
is called the “aura,” during which the dog seems to sense the
onset of a seizure and has brief changes of behavior such as
staring, stumbling, psychological depression, often the dog
will try to get to its owner. This phase usually lasts only a
few seconds and therefore is often missed. The second phase is
the actual seizure with falling, shaking of limbs, running
movements, loss of consciousness and loss of bowel and bladder
control being the usual signs. The third phase is the recovery
period and can last from a few minutes to an hour depending on
the severity of the seizure itself.
The third and another less
common form is the seizure that lasts for 15 minutes or more.
This is called “status epilepticus” and can cause damage or
even death if left untreated.
The origin of epilepsy can be
either genetic or acquired. Acquired epilepsy can be caused
by: 1) infections (viruses such as distemper, bacteria, fungi,
and protozoa such as toxo- plasmosis, 2) blood chemistry
problems (oxygen, sugar, salts, vitamins and toxic wastes); 3)
toxins (insecticides, lead, mercury, insect or snake bites);
4) trauma (head injury or electrocution); 5) tumors of the
skull or brain.
Of all of the causes of
seizures idiopathic epilepsy is by far the most common.
Idiopathic means that the causes are unknown although many of
them are known to be inherited.
The usual age of onset is 18
months to 2 years, but in beagles it has been seen as early as
3 months and as late as 9 years. Stress is often the trigger.
There is nothing in the dog’s health history to cause
suspicion. Lab tests and EEG (electro-encephalographic)
readings are normal, but if your dog has ancestors or
relatives with epilepsy and abnormal behavior as described
above, there is reason to suspect genetic rather than acquired
causes. Although both kinds manifest themselves similarly, and
are treated in the same manner, it is the genetic type with
which this article is most concerned.
An interesting and possibly
important variation of seizures occurs in our beagles.
Although most canine seizures occur around the age of 18
months, our beagles seem to have them at any age, late onset
being almost as common as classical type, with early onset
running third in number of occurrences.
It has been suggested that it
is possible that seizures during the middle years were just
milder and therefore missed observation. But it is my opinion,
since I know the various owners involved, that this
probability can be ruled out. These owners are conscientious
about their dogs’ health and welfare anyway, and because they
were aware of the possibility of seizures were looking out for
trouble. It is the owner who is uninformed as to what a
seizure is, or who isn’t looking for something unusual that
misses the seizures.
A second variation is that
beagles seem to have seizures that vary in intensity from mild
to moderate. I know of no cases in which the beagle reached
status epilepticus, and only one case of a purely non-show
line beagle that evacuated while convulsing. In the poodle,
especially the miniature, quite severe seizures are relatively
common.
Since the cause of most
epilepsies is unknown, treatment must be based on the clinical
signs. Genetic epilepsy is incurable, but in our breed totally
manageable. When required the most effective treatment is
anticonvulsant medications. There are a number of anti -convulsant
drugs which arc quite effective in controlling the number and
severity of the seizures. Currently, the three most commonly
used drugs are: Diphenylhydantoin (Di- lantin); Phenobarbitol;
Primadone (Mysoline). Most of the epileptic beagles I know of
do quite we I with no medication at all and have only
occasional seizures during their lifetime. On the other hand,
I know of a Miniature Poodle who was having as many as six
seizures a day at the age of three years and is now doing
quite nicely at the age of 10 on rather large doses of
Mysoline. When medication becomes necessary, it usually must
be continued for the life of the dog.
Although it seems that many
beagles do well without anticonvulsant medication, this is not
to say that dog that has had a seizure should go without the
care of a veterinarian. Sometimes the causes are correctable,
such as brain tumors, infections, metabolic disturbances or
scar tissue due to head injuries.
Although epilepsy should not
be taken lightly, neither should it be considered The Great
American Tragedy. The epileptic beagle can and does lead a
normal life, often without medication.
The owner’s responsibility is
to make sure that when a seizure occurs the dog will not be in
danger if help is not around. This can occur if the dog is
normally allowed to run loose (which I hope none of yours do!)
or if there is a pool in your yard, or if there are other dogs
around who might get aggressive in times of unusual
excitement. Even a beagle that normally avoids water could
stumble inadvertently into a pool and drown. It is also
important to keep other dogs away during a seizure as they
become quite excited, even agitated to the point of injuring
the epileptic dog or fighting amongst them selves.
If your dog has a seizure
while you are there, why not offer a little comfort? Many dogs
seem to try to get to their owners anyway, and it seems to
help to move them to a carpeted area and just sit with them,
petting them without obstructing their involuntary movements
and talking to them in reassuring tones. I know of one dog who
seemed frightened by the first few seizures, but with the
above attention from the owner, started accepting them as run
of the mill. The owner even felt that the recovery time was
decreased.
A good deal of our knowledge
of canine epilepsy has been inferred from studies done with
humans. Approximately 10% of the human population has a
predisposition to seizures, but never know it, because the
contributing factor(s) are never present. As in dogs, some
human epilepsies are caused by heredity and some are acquired.
In recent years, attitudes
towards human epileptics has supposedly improved, with
ostracism, social rejection and downright discrimination
becoming a thing of the past, but if the unhealthy fear and
lack of understanding of canine epilepsy is any example of our
progress, human epileptics must still be under a great
psychological strain.
GENETICS OF EPILEPSY
The genetics of epilepsy in
dogs has received some attention from the scientific world,
but no clear-cut mode of inheritance has been established.
There are six possibilities as to how it might be inherited,
but three of the ideas are just hypothesizing on my part.
These six possibilities are:
1. simple autosomal recessive
2. recessive but polygenic
3. recessive with an additive
effect
4. switch genes
5. modifying genes
6. genocopies
Simple recessive inheritance
is the most commonly held belief for inheritance. It means
simply that only two genes are necessary to show seizures, one
inherited from the sire and one from the dam.
Polygenic inheritance is where
many sets of alleles are needed to determine a trait. In this
case if the parents were at two extremes of a trait, such as
epilepsy with variations in age of onset, and in severity of
expression, the puppies would probably fall somewhere between
the parents in its expression.
A simple recessive inheritance
with additive genes is one researcher’s explanation for the
early onset of seizures. That is, as dogs (specifically
British Alsatians) become more inbred more genes which
influence the inheritance of epilepsy are added onto the
heredity of the dog, causing earlier onset. It was discovered
that by selecting for dogs with epilepsy, they automatically
selected more inbred dogs than their control group. In
following the lines for which I had the most information this
held in the sense that early onset puppies were more inbred
than the average, but their siblings who also had the same
coefficient of inbreeding, and had seizures did not
necessarily have them earlier than would be expected normally.
This group also had a
statistically significant difference in the ratio of males to
females having seizures. This has been observed by other
groups, but with the pedigrees I have looked at this is not
very convincing.
Another possible explanation
for the variability in age is what are called “switch” genes.
These genes cause changes in developmental pathways. If switch
genes, of which there are various types, are the cause, they
lend credence to the supposition that epilepsy alleles fit
into the category of polygenic, not simple.
A third explanation for the
age difference may be that epilepsy has genocopies. That is,
that it is not a single disease, but rather a set of diseases,
each with a different set of genes responsible for its
manifestation. It is possible that late-appearing seizures,
classical 18-month epilepsy and early-appearing epilepsy may
be genocopies, non-allelic, and there fore completely separate
genetic diseases.
If genocopies were involved,
think how complex the genetics would get if the dam were
heterozygous for both early-appearing epilepsy and
late-appearing epilepsy, and the sire was heterozygous for
classical epilepsy and late epilepsy. The unfortunate breeder
is going to end up with dogs that carry the genes for all
three forms of the disease.
Since seizures are sometimes
not seen in a dog that one would expect to have them due to
his pedigree, there might be a possibility of modifier genes,
or suppressor genes. Modifier genes do exactly what it sounds
like: they modify or change the expression of a trait in some
way. A suppressor gene actually suppresses mutant genes so
that the normal phenotype can be expressed. If either of these
types of genes were present, they could be responsible for the
differences we see.
It has been suggested that all
epilepsy may be environmentally caused since it seems to be
triggered by stress, and can be caused by trauma. It is my
opinion that the widespread incidence of epilepsy we see in
canine families cannot be due to environmental deficiencies or
excesses. A breeder who refuses to see that it is genetic and
is continually treating their dogs with nutritional
supplements in hopes of finding the magic potion which will
“cure” epilepsy is in for many heartbreaks. On the other hand
it is also my opinion that there are no traits that are purely
genetic in their expression; that is, environment can and does
influence the most dominantly expressed trait. Therefore as I
have tried to impress on the reader in a previous article,
give your dogs the most optimum environment that you are able.
Even superior genes cannot cope with poor environment.
BREEDING PLANS
In spite of my ravings about
the possibility of epilepsy being caused by various modes of
inheritance, and complicating factors such as switch genes and
modifying genes, in the great majority of pedigrees that have
studied the inheritance can be followed as a simple recessive.
This is not to say that the different forms are not real, but
in all cases, whether late or early onset, the parents carried
the genes for some form of epilepsy. It is for this mode of
inheritance that I will be giving suggestions.
There are several problems
inherent in trying any breeding plan with a defect such as
epilepsy:
1. A definite mode of
inheritance has not been established.
2. The age of onset is often
late enough to make delaying breeding impractical.
3. Gathering sufficient data
about the dogs in your pedigree to make intelligent breeding
choices may be difficult if other breeders can’t or won’t
cooperate.
In short, I have no pat
answers and your conscience must be your own guide as to
whether dogs who are most likely to have seizures should be
used for breeding at all. Epilepsy is not pleasant for the
owners, but it apparently doesn’t fall in the same category as
hip dysplasia, or PRA as far as those who are in a position to
know are concerned. The reasoning is that neither pain nor
permanent disability is a factor. They, like most of us, feel
that their dogs have other good qualities to offer their breed
which makes it worth taking a chance. Again, I refuse to be a
judge of your conscience, but since I have been asked on
several occasions how to cope with it in a breeding program, I
will give some suggestions.
There are two things you must
do before embarking on a breeding program. The first is to
find out as much about the dogs you will be breeding, whether
they are in your pedigree or someone else’s. The second thing
is to decide ahead of time what your priorities are. By this
mean don’t forget what you are trying to do. What good is a
line of beagles that is free of epilepsy but looks like
bassets, or can’t whelp properly, or has degraded to the point
that it bears no resemblance to the standard? In other words,
don’t sacrifice type and quality to produce soundness.
Lest some of you become too
smug because you have no epilepsy in your beagles, may I point
out that I know of cases of epilepsy in four separate and
distinct show lines. These lines are not new in terms of being
recognized nor are they related to each other within six
generations. Two of the four lines have no common ancestors at
all. I would be willing to bet that most of you have dogs in
your pedigree that are from at least one of these four lines,
and if you have been out crossing much, you could conceivably
have all four.
If your dogs are, as a whole
worthy, and you still want to use them, progressive dilution
breeding would be valuable, if possible. If epilepsy is a
simple recessive trait, this would mean that two recessive
epilepsy genes have to combine to produce epilepsy-manifesting
progeny. If neither parent has epilepsy, but both have the
recessive gene, this would produce puppies 25% of which will
have seizures, If your dog has an epileptic parent and you are
able to breed only to non-carriers of the epilepsy gene, it
will take 6 generations of this type breeding to be 98% sure
that you are free of the gene. Remember that statistics is
probability; you will never be 100% sure. This dilution
breeding can be followed no matter where the epileptic dog is
in the pedigree. Thus, if your own dog is the one who has
epilepsy it will take 7 generations of non-carrier breedings,
and if the problem is in the grandparent it will take 5 such
generations. To illustrate the point further, please refer to
the sample pedigree. tt = convulsive t = carrier
If the dog named Tyro is the
most recent occurrence of epilepsy it will take 5 generations
of breedings, starting with your dog Paragon to be free of the
gene. If Paragon’s dam, Laudable, is the most recent
occurrence, it will take 6 generations. If your dog Paragon
has had a seizure it will take 7 generations. This idea can be
followed for any generation on the pedigree. The further back
the occurrence, the fewer the breedings that are necessary.
Please remember that if at any time a dog with seizures is
produced, it is the same as starting back at the beginning
with Paragon. It also means that your supposed carrier-free
dog is not free at all.
It is also important to note
that if you are able to use this kind of breeding, it doesn’t
matter how many times epilepsy occurs in your present
pedigree.
But how will you know that
your breedings are to dogs totally free of the gene? If the
breeding program is within your own kennel, have your sires
test-mated to a bitch that has epilepsy. For a puppy to show
the recessive defect, it must get one gene from its sire and
one from its dam. If your sire was a carrier and bred to an
epileptic bitch, each puppy would have a 50% chance of having
epilepsy and 50% would be free of seizures. Given enough
puppies, the seizures will show up if your stud carries the
gene. If no puppies have seizures, and enough puppies have
been produced to eliminate chance, you probably have a stud
free of the gene. Seven puppies free of the seizures will give
you a 99% chance of being free of the gene and I think this is
reasonable.
The problem that arises here,
of course, is the waiting period and the fact that every
single puppy produced will be a carrier of the defect. And, it
you have to test-cross your dog to a carrier instead of an
epileptic, a relatively safe number of pups without seizures
would be more like fifteen. But no matter how you deal with
the test breeding remember that there are no absolutes! Also
please note that dogs that have been misdiagnosed and used in
test-breedings will thoroughly mess up the whole business.
Please remember also that seizures show up at different ages,
and allow sufficient time to pass before concluding that your
dog is not a carrier.
For the great majority of
breeders the mating of totally normal dogs, i.e., non-carrier
dogs, will not be possible or practical every time. I have
some suggestions for this situation, but no guarantees.
Since a recessive gene does
not reveal itself in the carrier state the breeding of dogs
that have not had a seizure is not necessarily breeding clear
to clear. In fact if your dog has an epileptic parent, he is
definitely a carrier. The ideal mating is normal to normal,
next normal to carrier. Neither of these dogs would have
seizures, but 50% of them would be carriers.
Using the sample pedigree
again as an example, please notice that Famous is a carrier
for the gene and that Hero, as FAR AS WE KNOW, is not. If Hero
were bred to Famous, 50% of the puppies would be carriers.
Next down the desirable scale
would be the affected dog bred to the normal dog. In this case
we might breed Paragon back to her grandfather Hero. This
might be a risky breeding since Paragon may have gotten her
defective gene from Hero’s portion of the pedigree, but the
evidence is that the carrier gene came from as far back as
Wellbred on her granddam’s side. Notice how elusive and sneaky
the carrier state can be. The gene for epilepsy was hidden for
four generations before it turned up again. This breeding
would result in all of the puppies being carriers for
epilepsy, but none of them having the seizures.
Another breeding might be the
afflicted dog bred to the carrier dog. In our sample pedigree
we might breed Paragon to Wellbred, if we felt that his
virtues outweighed the fact that he has produced epilepsy.
This would result in 50% of the puppies being affected and all
of the puppies being carriers.
Of course the final possible
breeding would be the epileptic dog being bred to another
epileptic dog. In this case all of the puppies would have
seizures at some time in their lives.
DISCUSSION:
In breeds where epilepsy is
more serious than in our own, there is a general unwillingness
to admit that it exists or to consider it as a serious defect,
when they are more concerned with PRA or hip dysplasia or
both. There can be no upgrading with regard to the disease if
owners and breeders refuse to admit it exists.
It is all well and good to
talk about the promotion and improvement of beagles, but we
can do this only if the owners are honest in their dealings
with one another. Although there can be minor modifications in
the number and severity of seizures by environmental changes,
it is by far the majority opinion of geneticists that epilepsy
is of a genetic nature and that the effects of external
environment are of minor significance.
Among the factors that will
retard progress in reducing the incidence of epilepsy are:
1. ignoring the problem
2. rationalizing away the
genetic factors of epilepsy
3. basing your breeding
program on insufficient or incorrect data
4. dishonesty about the
carrier status of your own dogs
5. breaking down honest
communication by GOSSIP and WITCH-HUNTING!
By early detection and removal
from the breeding population of the affected dogs we reduce
the chance of increasing the problem, Insofar as possible the
avoidance of breeding affected dogs roust inevitably result in
fewer carrier dogs being born, and in the lower number of
affected puppies being produced.
IF NONE OF THE ABOVE WORKS,
CALL YOUR LOCAL EXORCIST!
I would like to express my
appreciation for the tremendous help and cooperation of
several breeders, who were so generous and honest with
information and pedigrees. Since it is not my place to give
out names, these people and their dogs must by necessity
remain anonymous, but they know who they are. Thank you.
GLOSSARY
ACQUIRED CHARACTERISTICS: any
trait produced by environmental causes.
ADDITIVE EFFECT: intensity of
expression based on the number of genes present for production
of that characteristic. Also dosage effect.
ALLELES: alternate forms of
genes which occur at the same point (locus) on a matched pair
of chromosomes.
AUTOSOME: any chromosome not
involved with sex determination.
CONGENITAL: present at the
time of birth, but not necessarily genetic.
EXPRESSIVITY: the degree of
severity of phenotype.
GENOCOPY: identical or very
similar disease with different sets of alleles involved.
GENOTYPE: the total gene
complement in an individual.
HETEROZYGOUS: having
contrasting alleles at a given locus, i.e., hybrid.
HOMOZYGOUS: having the same
kinds of genes at a given locus, i.e., pure.
IDIOPATHIC: arising from an
obscure or unknown cause.
LOCUS: the position on the
chromosome for a given pair of alleles.
MODIFIER GENES: genes which
effect expressivity. PENETRANCE: the degree to which genotype
can be deter mined through phenotype.
PHENOTYPE: the physical
expression of genotype includes biochemical make-up as well as
physical.
POLYGENIC: genetic pattern
involving two or more sets of alleles.
PRA: Progressive Retinal
Atrophy, a genetic eye disease found in many breeds.
SUPPRESSOR GENES: genes which
allow the expression of normal genes in spite of the presence
of mutant genes which might block or modify the normal
phenotype.
SWITCH GENE: genes whose
action causes a switch of the genotype to a different
developmental pathway.
SYNDROME: a set of symptoms
that occur together in a given disease.
TRAIT: the special
manifestation of an allele. Also any phenotype whether
physical, biochemical or behavioral.
BIBLIOGRAPHY
Barker, J. Epilepsy in the
dog—a comparative approach. J. Small Anim. Pract. 14:281-9 May
73.
Cunningham, J. G. Canine seizure disorders. J. Am. Vet. Med.
Assn. 158.589-597. 1971.
Dahme, E. and Brass, W. Epilepsy in dogs. Clinical and
morphological reflections. Berl. Munch. Teiraerztl Wochenschr
88 (13):248-53, 1 July 75.
Falco, M. J.; Barker, J.; Wallace M. E. The genetics of
epilepsy in the British Alsatian. J. Small Anirn. Pract. 15
(11)685- 92, Nov. 74.
Hegreberg, 0. A.; Padgett, 0. A. Inherited progressive
epilepsy of the dog with comparisons to Lafora’s disease in
roan. Fed. Proc. 35 (5): 1202-5, Apr. 76.
Kay, W. J.; Fenner, W. A. “Epilepsy” in Current Veterinary
Therapy. Vol. VI.
Lemieuz, J. C. Idiopathic epilepsy in dogs. Can. Vet. J.
18)10:292-5, Oct, 77
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