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Welcome to the official podcast of the World Small Animal Veterinary Association, where we bring you conversations with leading veterinary experts from around the globe. Each season spotlights one WSAVA committee, sharing their knowledge, research, and insights through short, accessible interviews.
Every fortnight, we speak with two experts on a shared theme, offering concise, engaging discussions designed to spark curiosity and guide you toward WSAVA’s extensive library of educational resources, webinars, and events. Hosted by WSAVA President Jim Berry, the podcast delivers focused conversations that connect you with the latest thinking in small animal medicine worldwide.
You can find more educational resources from WSAVA here: https://wsava.org/education/
Welcome to the WSAVA podcast.
This episode looks at the genetic
side of common diseases, the hidden
inheritance patterns that influence
patient health and treatment.
As you listen, ask yourself, how might
a genetic perspective change the way
you explain these diseases to owners?
Our host, Wolfgang Dohne Speaks first with
Ursula Dietrich, then with Patrick Hensel.
Let's hear more.
What are probably the most inherited
ocular diseases of the feline
patients that you encounter?
Certainly those brachycephalic type
cats, which are hugely popular.
For instance, the British Shorthair
falls in this category, or Persian
cats, so these are very popular cats
and brachycephaly, it's not a genetic
test available for this as such,
because it's a polygenetic problem.
Very likely many factors come into this
and we cannot test for that as such.
But what is certainly possible is
to, like in dogs it's done already,
looking at more healthier looking
confirmations that don't cause issues
such as chronic corneal ulcerations
or discharge from eyes, et cetera.
So these are all problems that
come with breeding into a certain
aesthetic in these breeds.
So clearly that is something that needs to
be investigated much further in the future
and have also responsible breeding for
these cats, and as veterinarians, we have
a huge responsibility for that as well.
How is that, especially while we talk
sort of brachycephalic cat breeds,
how is that with the composition
of the tear film of these cats, is
that also an additional complicating
factor in a lot of these cats?
Yes.
So it's a huge, depending how
bad the brachycephaly is, depends
how short nose this cat is.
The eye relatively to the
head proportion are huge.
They're protruding slightly and
lots of research has been done to
actually test the sensitivity on
the cornea, so we know they have
the least or less sensitive surface.
But also, of course, the tear
film is utter most important
for corneal health overall.
So if you have a, an animal or a cat
that cannot really blink properly or
close the eyelids completely, that
will have an effect on the tear film.
So many of these cats, they do have
chronic issues, so testing for their
tear film quality and quantity is very
important and to find for this individual
cat the best treatment at that time
and prevent things from happening.
There were quite a few studies in the
past few years that looked at the overall
population of cats in larger referral
centers and it looked which cat types
had the worst problems or the most
problems, and also what type exactly does
it filter down in these particular cats.
Of course the number one were
ulcerations or also corneal sequestrum,
for instance, in these brachycephalic
breeds is a common problem we see.
These are the things which we need to do
in the future even more to monitor and
see what are emerging diseases and then
eventually we may be able to look further
and look, is there any test available
in the future that can test for those.
We know, for instance, the corneal
sequestrum is a really interesting
topic that is getting bigger and
bigger the more questions you ask,
it's not just one corneal sequestrum
there are different types probably,
and also different presentations of a
sequestrum, different types of treatments.
So it's not always surgical, but often.
And so yeah, we have to look
into many different aspects
of this condition as well.
But clearly there's a cluster in
some breeds where we know it's
much more common than in others.
Breeder advice is, in that
situation, I think ever so
important, that we have a look at
it in how far is this suitable cat?
Even how some breeders are, they
think that their line is the most
precious line in the world, even
if these cats clearly suffering.
To tell these breeders, 'No, it's
probably not a good idea to go down
this road because it's unlikely to get
much better, and conformation problems
might actually get worse this time.'
Exactly.
It's such a big topic, so it's not just
breed predisposition, but of course it can
be secondary to chronic herpes infection
or it can be mechanical irritations.
That kind of is a nice transition now
to the next problem that is, seems to
be emerging, which is entropion in cats.
When I was in that school, we
hardly ever saw cats with entropion.
It was literally a non-existing condition,
maybe in cats that were much older,
where we know the orbital fat disappears
and it becomes a bit more lax and they
get this kind of older age entropion.
But we are seeing now, are breeds
where we have a huge cluster of this
condition and number one at the moment
is certainly the maine coon cat.
They're lovely, really sweet cats.
There is a huge pressure on breeders to
breed these cats to have these desirable
traits of being really big and so on.
So this causes other issues down the line.
entropion, it's very likely multi-genetic.
It's not just one single
gene causing that.
It can be environmental factors as
well that influence these things.
So it's a big topic, but what we as
veterinarians and ophthalmologists
need to do is register and look closer.
Is this very familiar in these cats?
Is the whole family affected,
father, sons or offspring, siblings?
It's so important to look at this
first and make these recordings
and documentations properly.
And that would be probably
the start to find out is there
actually problem in this breed?
Of course you can fix this for the
individual cat and you can do surgery, and
they have a very happy life afterwards.
But it's really horrible to see
sometimes these younger cats,
they're less than a year old.
They have bilateral severe entropion in
the lower eyelids and the only way to
fix that chronic ocular discharge and
pain and possibly ulcerations is surgery.
When we look at the x-ray of
brachycephalic cats, I see the whole
front of the skull or different
sectors of the skull are deformed.
Something that we quite often see is then
issues with corneal issues because of the
difficulties providing protective film,
for example, and the entropion issue is a
problem, but is there also a problem with,
say, pressure in these cats on the optic
nerve, for example, or is also the retina
affected because of brachycephalism?
So it's not direct an effect on the
retina there, but what can be affected,
and this goes more in the neurology
territory, so their skull can be too small
to accommodate their brain and they can
definitely get neurological problems.
If we talk about retinal diseases,
that's another very interesting topic,
and this is probably the one where we
have the best genetic research done,
and also there are tests available.
If there are breeds that come
with visual deficits because
this is blinding these cats.
When I came over to the UK and I
started practicing now over good 12,
13 years ago, I remember I could not
believe how many domestic like Moggie
cats where you don't have obviously
a breed identified phenotypically.
But these cats, they had retinal
degeneration and they would present
with, at the age of seven or
eight, and they were completely
blind with the retina looking
completely degenerated bilaterally.
And so everyone who is listening
in and has seen PRA in dogs, yes,
absolutely this does exist in the
cat as well and the symptoms are very
difficult to detect in cats early
because cats are masters in hiding.
If you have a blind cat, they just
don't walk around like a dog does.
So you have to do much more specific tests
here to find out and always look into the
retina, of course, do an ophthalmoscope
examination because we can pick up
potentially these things much earlier.
But saying that, yes, there are
definitely genetic variants and the
number one cat that always has to come
up in these retinal discussions is the
Abyssinian, where this was one of the
first breeds where we found problems
and two different types later onset
degeneration, early onset, but we now
have the means to actually identify
these genes that cause these problems.
And so it's the Abyssinian, it is
the Persian again with the condition,
it is the Bengal cat with a retinal
degeneration that starts again early
on, which we have identified the gene.
But the problem is if there are
closely related breeds, like with
the Abyssinian for instance, there is
the Somali, which is the long-haired
Abyssinian, similarly affected.
But then there are these oriental breeds
that have these cats in their line because
they were outcrossed and so basically
this recessive gene slowly goes into
other breeds and so we know there are a
huge amount of other cats now that are
descendant from these original breeds.
They have this gene somewhere and this
is so important to monitor and to find
out which are these affected ones.
The progression of this condition from
say, really very early signs until
developing into complete blindness,
how long does it usually take?
And also are both eyes equally affected in
these patients, or is there a difference?
Yes, these retinal degenerations that
have a genetic underlying problem,
most of the time there's a problem in
the photoreceptor physiology, so there
is a gene that is coding for protein
necessary for this whole vision process.
And if this is lacking or it's
not functioning anymore, that
is when these diseases happen.
In the early onset ones, we probably
have a kind of a dystrophy as well.
These cats already are born with
having issues but these are breeds
where we may not find them in a
generalized cat population only.
However, in these cats where we
know they have that gene that the
abyssinian had, CEP290 gene, that
one can cause blindness usually about
between three or five years of age.
But some of these cats may become fully
blind a little bit earlier, so there
could be a wider variation, which again
shows that genetics are not that far
forward because we don't know, are
there other factors that factor in?
Other genes that come into the
variation in these cats as well?
It seems like these days that
mutation always has a very negative
kind of conception because it
can be also a good mutation.
So we call these a variation of a gene.
So this sounds a little bit more benign
because the variation, again, can be
bad, can be good, or could be neutral.
So there may be no effect at all.
So it's very, very interesting
to see what evolves for that.
Late onset PRO or normal PRA, and
then late rod cone degeneration,
if we look at the clinical findings
of these two conditions, do they
progress and present in a similar way?
Owner comes in and the cat is
progressively showing signs of
blindness or is one or the other faster?
This is the problem in cats and I
think I recall a publication I was
reading where we found that in some
cats it may be completely masked
because they're hiding this so well.
So it's really overlooked that they
actually, their retinas is disappearing
in front of our eyes, so to speak.
And the classic signs you would look
for it's compared to dog, for instance,
you look at the blood vessels, remember
the cat is like the dog holangiotic.
So we have clearly retinal vasculature
so we can look at these blood
vessels, are they sending over time?
And then this big, huge tapetum that
cats have what we call hyperreflectivity.
It means that the sensory retina
gets thinner and thinner because it
degenerates and then what happens is
the tapetum lucidum underneath becomes
much more prominent and more reflective
looking and so this is exactly one
of these key symptoms you will see.
In the most latest stages, the optic
nerve also atrophies completely.
So you have, literally looking at a retina
that has hardly any blood vessels left.
It's hyper reflective and a very small,
even smaller and darker optic nerve.
So these would be bilateral findings and
I've been surprised in my patients, I've
seen over the years how you look at this
cat and you think this is impossible that
this cat is completely blind and you look
at the retina and it's completely gone.
And so this is again, the problem
where cats pose a little bit more for
difficulty because they can still jump.
Even if they're blind, they can still
do things that an owner would not
necessarily think it's a problem.
Another symptom you could find in
the late stages is the pupil size is
very important in cats to look at.
So if the pupil is not constricting
anymore and there is this tubical
slit you normally would expect in a
constricted pupil is no longer happening.
You should flag that up and look at
it and not just look at the retina.
And that comes to different
condition, which is glaucoma.
So glaucoma in the cat is another one
of these conditions that is so masked
by cats because they show no sign of
pain, even if the pressure is forty or
higher, you would get a cat that has
the really high pressure and the eye
looks relatively normal, comfortable,
but maybe one of the signs you could
potentially see is a dilated pupil.
One part of the eye we haven't
talked about so much is the lens
luxation, also another condition
with hereditary background, when do
you see these cases predominantly?
Are these also more younger or older cats?
Lens and cataract is another
really interesting one, which is
under rise in a lot of breeds.
Russian Blue, Bengal, Persian,
British Shorthair, so all these
cats suddenly come with cataracts.
Now, lens luxation, I've seen British
Shorthair cats less than a year
old with lens luxation, which we
did not find an underlying problem.
The primary lens luxation in the
domestic shorthair is well documented.
It could be just, again, multiple factors,
multiple genes causing this issue.
So we don't quite know yet
what the genetic background is.
But yes, these cats will be very likely
young and they have an issue from an
early age on versus lens luxation in
the older cat very often is secondary
to say chronic uveitis, chronic
inflammation in the eye, which then
eventually leads to lens luxation.
So these are completely
two separate issues here.
Lens luxation secondary to another
problem and a primary lens luxation in
younger cats, maybe in certain clusters
of cats, which we have not identified.
And hereditary cataracts?
Yeah, that's another super interesting
topic because the description of
cataract in cats where presumed
to be primary goes back long time
into seventies of the last century.
So these were descriptive presentations
in the Persian, but now we know
there is more and more breeds present
with cataracts that are bilateral.
If you have a genetic component
presumed to be inherited, most
of the time this is bilateral.
And ideally you need a slit
lamp to look where exactly
is this opacity in that lens.
And most of the time in these primary
type of cataracts in the cat where we
think they inherit it, they start in
the more posterior part of the lens.
They can be central lens as well.
And they have a tendency not
necessarily to develop further.
We see already differences here and
then the cat coming with these maybe
minor incipient cataracts, and they,
of course, they don't show that.
This is a completely different
problem we are dealing with in the
cat compared to the dog, where you
pick up these things much quicker.
What I often say to my clients that
have these cats with retinal atrophy or
mild forms of cataracts, I'll say that
they don't have to read any newspapers.
They don't have to operate any heavy
machinery and they are amazing in the
way they can adjust, you know, so there
is unfortunately not much I can offer
them to improve the condition, but
at least when it comes to the quality
of the life of these cats, especially
if they're, uh, been strictly indoor
cats that are still not too bad.
But obviously if you look at it from a
geneticist point of view, certainly not
cats and individuals you should breed from
and if you are breeding a cat breed that
is frequently seen with this conditions,
to test early if the test is available.
After Ursula Dietrich, Wolfgang
is joined by Patrick Hensel for
the second part of this episode.
This podcast is dealing with the important
of inherited diseases and in genetics.
What's your own impression?
Are we more aware of this?
Is it more important?
I think there always have been
hereditary genetic diseases, congenital
diseases, not very common, they're quite
rare, but the hereditary conditions,
especially with the area of breeding,
these kind of conditions and problems
become more prominent and more common.
Atopic dermatitis, follicular dysplasia,
color dilution alopecia is something
which you see very common nowadays and has
definitely also like a hereditary base.
There are several diseases which
seem to be more common than others.
We are specialized in dermatology and
we only do see dermatological patients,
and so some of these hereditary
diseases do appear in our practice more
frequently than in general practice.
From my perspective as a general
practitioner, I see two situations.
One is that a breeder comes through the
door with very specific expectations
for information because of the specific
breed they have or the other situation
is that a case just doesn't work out
as expected with standard treatment.
And I think, well wait a moment,
might this be something genetic?
It's an uphill struggle and I
will probably never improve this
condition and then this is also
usually the situation where I call
in the help of somebody like you.
Well, the thing is, is hereditary
diseases are not curable.
They can make the overall
situation worse for the patient.
Let's say atopic dermatitis
as a multifactorial disease.
Genetic plays one role of it in certain
degrees, depending on breed family,
and the higher the risk or presence of
the hereditary or genetic disease is
present, it's more difficult to manage it.
And most of the diseases are
chronic, you know, atopic disease,
follicular dysplasia, sebaceous
adenitis, for example, is
suspected to have a genetic base.
So these are all chronic diseases
that you have to manage lifelong
and that can be quite difficult.
If we look at the clinical aspects
of canine atopic dermatitis, how
big is the inherited versus the
acquired effect of the disease?
It is so that there are certainly
dogs that are pre positioned to, and
they have gene defects and will be
atopic but then I think something
that is also really important is what
sort of environment they are raised.
Also, their exposure to certain
factors that then trigger the clinical
presentation of the condition.
Can you say it's a 50 50 situation,
or might you say actually the genetic
background is even more important?
Oh, the genetic background is usually
lower than 50, but there have been
studies where they looked into the
heritability in certain breeds.
I think there was like one publication
2004 in the UK where they looked
into guide dogs, Labrador and Golden
Retrievers, and they had I think 430
dogs and they were related to 13 dogs
which had canine atopic dermatitis.
And then they looked into what's
the degree of heritability.
And in that pace, um, it
was basically almost 50%.
So that means basically the risk of
developing canine atopic dermatitis in
this population was, genetic alone, 50%.
Usually it's lower.
You have the environmental
factors then on where you grew
up, how you are fed, et cetera.
I would say usually it's like in
the lower teens, but again, this
was probably a population of dogs
with good traits and then they
got a little bit probably inbred.
And then if you use always the
same parents who have severe canine
atopic dermatitis, then you certainly
will see it in the offspring.
If we look into the pathophysiology
of canine atopic dermatitis,
what do these gene defects do?
How do they manifest or what,
where do they cause problems?
There are different factors which can
be affected by these genetic variations.
Probably one of the big ones
is the skin barrier defects.
That's due to changes of the proteins.
The laminin-5, for example, is like
a protein of the skin barrier, or
important for the skin barrier, which
is very important in humans, it hasn't
been shown to be as important in
dogs, but it may be in some breeds.
And then certainly other genetic
variations which are involved atopic
dermatitis are by upregulating
inflammatory cytokines or downregulating
anti-inflammatory cytokines.
So it's certainly more immune
mediated factors, which can be
affected by the genetics or the skin
barrier defects or abnormalities.
And also neuroinflammation is certainly
a factor to, to take into account
here, to just makes the skin generally
more sensitive, even if the skin
barriers are not necessarily certain
dogs that aren't more sensitive,
even to a very mild stimulus.
We have certain breeds where they
are probably more susceptible to the
environmental allergens, which triggers
faster and inflammatory response.
The problem with the skin variant
and inflammation, most of the time
they will play together because if
chronic inflammation of the skin, you
will obviously have a change in the
composition of the sebum of the skin,
which is important for the skin barrier.
And over time you will have also
problem with skin barrier defect,
whether this is a direct problem or
indirect due to the inflammation,
that can vary from case to case.
What are the most affected dog breeds?
Obviously we are talking here to a
worldwide audience, so there might be
some other breeds which are just not
so common in Switzerland, but that
are still on the top of the list.
Sure.
Yeah, and definitely depends on the
current popularity of the breeds.
20, 30 years ago it was the
West Highland, which was the
prototype of atopic dermatitis.
Nowadays I would say we see a lot of
bulldog type breeds, French bulldogs,
Continental Bulldogs, English bulldogs.
This is not just allergies, they
have all kind of skin issues, and
it's amazing how many of these
patients show up in our practice.
What tests are there to identify gene
defects here that are responsible
or play a role in atopic dermatitis?
The problem here is that atopic dermatitis
is a multifactorial disease and there
is no specific one gene, which is
responsible that we call it sometimes
a polygenetic disease because depending
on the continent, depending on the
breed, you may be dealing with totally
different types of genes involved.
There's a lot of research going on in
identifying genes which are involved
in that canine atopic dermatitis,
and maybe to use them as a biomarker
then for genetic testing, which
might be helpful for the breeding.
Also, to identify biomarkers
for future treatment options,
development of medication.
But currently there is not really
much available on the market.
But there's definitely a lot of
experimental ones floating around.
And in some instances you may submit
samples for the studies so they can
use it to, to develop these tests.
But currently there is not really any
genetic tests we as dermatologists
use to identify this atopic,
genetic based atopic disease cases.
The diagnosis is still based on
clinics, allergy testing, et cetera.
Mm-hmm.
Which is interesting because if we
look at fur and color variations in
different dog breeds, there are a lot
of genetic tests and sometimes very
specific tests, which the breeders jump
on and they have a whole list of tests
they often want to have done, but when
it comes to such a common condition
as atopic dermatitis, interesting that
at least until now there is so little.
Yeah.
One thing is because there's so
much variation of the colors,
you have this whole set of genes
which are involved and that's it.
But then atopic dermatitis
is a moving target over time.
It also may change depending on the
breeds, and there are probably many
genes which we don't know yet, which
might be involved in atopic dermatitis.
Yeah, although some genes are already
known to cause a problem and once you
know what you're looking for, then
usually a test, a biomarker, should
be identifiable and that is obviously
also something you then measure.
From the biomarkers, yeah, we know
that there's a set of biomarkers which
potentially might be valuable, it's
just not established yet, but they
probably have to use it on a much
bigger population, and again, the one
biomarker which may work well in the
US or in Europe, may not work that
great in another continent because the
genetic settings that are different,
even if it's in the same breed.
What is the advice if you have a dog
which somebody would like to breed from,
but this particular dog is developing an
atopic dermatitis, is it still okay to
breed from the dog, or is it also then
specific from dog breed to dog breed?
Is there a variation?
I guess what plays an important
role is the severity of the disease.
You have dogs with mild disease,
then you can say, okay, maybe you
can still breed with this dog.
Generally we would say better not, but
then depending on the breed, you may
narrow down the gene pool so much, then
you may end up with other problems.
So I think it depends a little bit on the
population size of that specific breed,
but we certainly tell owners who might
be interested to breed, if you have a
obviously severe allergic patient, you
definitely should not breed with them.
It's sometimes difficult to enforce that
because again, atopic dermatitis is not
a clear cut genetic disease, like other
diseases where you can do genetic testing.
Since we don't have these tests and
we know that it's multifactorial and
environmental plays a role, there are
certainly dogs which are predisposed
but never will have problems.
So it's always a little bit difficult
to enforce that and tell the client,
no, you cannot breed with this dog.
But I usually tell the client,
if this is a obviously severely
allergic dog, then definitely not.
Thanks for joining us on the WSAVA
podcast where we are transforming
care one episode at a time.
We hope today's discussion was
helpful wherever you are in the world.
You'll find more information and further
resources on the topics discussed in the
show notes, and we look forward to sharing
our next conversation with you very soon.