A research update
By Clare Rusbridge and Penny Knowler
Stone Lion Veterinary Centre, 41 High Street, Wimbledon,
London, SW19 5AU
email@example.com (CR) firstname.lastname@example.org
The DNA collection is nearing completion of the first
phase. We are well on the way to having enough DNA for a
genome scan so a big thank you to all of those pet owners,
breeders and their veterinary surgeons that are so
dedicated to the health of Cavaliers. The first phase
involved collection from top bitches and stud dogs. Several
of the breeders contacted have already donated from their
dogs and others have promised to arrange sampling. The
genetic profiles from these dogs will be compared to
Cavaliers with syringomyelia, mitral valve disease and
We are still collecting from dogs affected with
syringomyelia and their close relatives with over 150
samples to date.
The next phase of the DNA project is collection of DNA from
Cavaliers with mitral valve disease. We are focusing on:
dogs over 7 years of age that have clear hearts; dogs with
heart failure less than 7 years of age; dogs related to
dogs with heart failure less than 7 years of age. Any
assistance in obtaining DNA from these groups is
Answers to common questions
Who are the geneticists involved with this project?
Dr. Berge Minassian and team work at the centre for Applied
Genomics at the Hospital for Sick Children in Toronto. This
laboratory encompasses five state of the art core
facilities: DNA sequencing and synthesis; genetic and
statistical analysis; gene isolation and expression; genome
resources; and microarray. These resources are essential
for identifying disease genes.
Dr. Guy Rouleau directs the Neurogenetics laboratory at the
Centre for Research in Neurosciences. Over the last
15 years, his research has focused on the genetic basis for
diseases of the brain. He has mapped over 20 disease
loci and has significantly contributed to the
identification of over 10 disease-causing genes.
What is the geneticists' experience?
Drs. Berge A. Minassian and Guy A. Rouleau each have
extensive experience in identifying disease genes in
humans. Dr. Rouleau has participated in the discovery
of the genetic causes of amyotrophic lateral sclerosis
(ALS; Lou Gherig's disease); Juvenile Myoclonic Epilepsy; a
form of muscular dystrophy; brain vascular malformations;
and neurofibromatosis to name a few. Dr. Minassian
has discovered two human epilepsy genes and also works on
the genetics of canine epilepsy. Both researchers
head large world-renowned labs with extensive resources for
the identification of disease genes. They will
combine their strengths to help discover the genes causing
syringomyelia, mitral valve disease and epilepsy in the
cavalier King Charles spaniel.
Why work with scientists in another country?
We have worked with Dr Berge Minassian successfully over a
period of years in the genetics of a canine epilepsy
syndrome that is inherited in 3 different breeds. He
is familiar with our work on syringomyelia and provided
expert advice when required. An advantage of working with
scientists who are studying the human form of the disease
is the availability of greater resources especially as
genome scans are extremely expensive. Ultimately it
will also help children with similar diseases. In a truly
international spirit, Cavalier breeders from the USA,
Europe and Australasia have offered to send DNA and
information to Canada which will provide joint ownership of
How long will it take to find a gene marker?
Many years -- the current estimate is 3 years after enough
DNA has been collected.
That is too long -- I need to know what dog to use now!
We appreciate this; however we can see no other solution.
Even with our knowledge of the pedigrees, we cannot tell
which dog is safe to use and which is not because both
syringomyelia and mitral valve disease are so widespread in
all CKCS lines. The faster that DNA is collected and the
more that people cooperate and work together then the
quicker a blood test will be available
If my dog is providing DNA will you be able to tell if they
are a carrier for a disease or not?
No. There is no way of telling this until we have a marker.
I don't want to provide DNA because I am scared that my dog
will be identified as having the disease.
The information is and will remain confidential. The DNA is
being used to find a marker for the disease and hundreds of
samples of DNA are required, each identified by a unique
number -- not the dog’s pedigree name.
Do we know anything about the status of the littermates of
a dog affected with SM?
The status of these dogs is unknown. There is no way of
telling -- that is why a blood test would be
useful. Syringomyelia has a complex inheritance
like MVD, which is why it cannot be bred out in a simple
Mendelian manner. It is considered best to err on the
side of caution and use siblings as if a known
carriers i.e. sparingly and keep track of offspring. Signs
of syringomyelia are usually apparent by 3 years of age so
it would be safer to delay breeding until that age.
If there is a repeat mating where the first litter were all
unaffected, would the second litter also be clear
Do the dogs still scratch and have pain after
surgery? How long it is before an improvement is
Clare Rusbridge performs a decompression surgery where the
occipital bone and part of the first cervical vertebrae are
removed to create more space for the brain. The dura is
also incised and resected. Most dogs are much more
comfortable after surgery and can return to the normal
activities that were not possible pre surgery, for example
being taken for a walk. Most continue to scratch but
this may only be when very excited e.g. when greeting the
owner. Most dogs take 2 weeks to get over the surgery. From
then on most owners report improvement. Long term results
(>3 years) are not available in significant numbers.
Some surgeons prefer to place a tube in the syrinx and
report excellent short term results. However the long term
results for this procedure are not published yet. One of
the problems with shunt placement in humans is that the
tubes are prone to blockage and long term results are not
What are the risks of surgery?
There are major blood vessels in the area and if
traumatised the dog could quickly bleed to death. Although
not actually operating on the brain/spinal cord, it is in
close proximity and there is a risk of permanent
neurological injury. In my hands this has not happened yet
but it is always a serious possibility (CR)
What post surgery drug treatment would you advise?
Dogs are hospitalised until comfortable enough for
morphine-like-drugs to be discontinued and then discharged
on a combination of non steroidal anti-inflammatory drugs
(e.g. Rimadyl) and gabapentin (Neurontin). This is
withdrawn after about 2 weeks (CR).
Would prednisolone have to be continued after surgery?
I have never needed to use prednisolone in the immediate
post operative period. I have one patient currently on
prednisolone where the surgery failed after about 6 months.
Since this patient I have modified the surgery (CR)
What if a group of breeders wanted to get their breeding
dogs MRI scanned
before using them? How would they go about it?
Who should they approach?
Where are the scanners? Could a special price be
I would suggest approaching your nearest veterinary MRI
service provider and asking. Speaking from my own
perspective it should be possible however not on an
individual basis. In other words a group of dogs would be
done on the same day and there would not be a great deal of
flexibility about the day. A special price could be
negotiated (we are investigating this) but MRI is expensive
-- full stop. We charge MRI routinely at £810 + VAT
(including the anaesthesia etc) and make very little profit
from this It is only the profit which could be discounted.
There are two types of MRI service providers. The first use
the facilities of local (human) hospitals -- they are less
in control of the price as are being charged by the
hospital. The second have their own units and are therefore
more in control of the price however will have invested
hundreds of thousands to millions of pounds/dollars in the
technology and therefore must justify their investment and
cover the running costs. It would be easiest to ask your
vet where your nearest MRI service provider is. The most
likely are the hospitals associated with RCVS or European
Specialists in Neurology (Europe) or Diplomates of ACVIM
(neurology) in the USA. (CR).
There are some MRI schemes already up and running for
example the HEALEY STUDY. For details contact Joseph A.
DeLucia DVM,CCRP, Valley Veterinary Rehabilitation, 1171
Valley Road, Clifton, New Jersey 07013, 973-509-5225 ext
103, Fax) 973-509-6082, www.valleyvetrehab.com, Veterinary
MRI and RT Centre of New Jersey, 1071 Paulison Avenue,
Clifton, New Jersey 07011 973 772-9902,(Fax) 973-772-9904,
How early could you MRI screen breeding stock?
To answer this question would require a study where normal
CKCS and those that will ultimately develop syringomyelia
would have serial MRI to see when signs are first
detectable and to relate the size of the back of the skull
to the likelihood of getting the disease. This has not been
done yet. Most dogs develop signs of syringomyelia by 3
years; therefore 3 years is probably the most appropriate
age to scan, 2 ½ years at the earliest.
If my dog does not have syringomyelia on an MRI scan is it
guaranteed not to carry the disease?
Finally, we should like to acknowledge Boehringer Ingelheim
Limited (Vetmedin ®) and the UK DNA Archive for their vital
contribution towards the DNA collection programme.