By Clare Rusbridge and Penny Knowler
Stone Lion Veterinary Centre, 41 High Street, Wimbledon, London, SW19 5AU
firstname.lastname@example.org (CR) email@example.com (SPK)
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 epilepsy.
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 appreciated.
Answers to common questions
are the geneticists involved with this project?
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
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.
work with scientists in another country?
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 any success.
long will it take to find a gene marker?
years - the current estimate is 3 years after enough DNA has been collected.
is too long - I need to know what dog to use now!
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
my dog is providing DNA will you be able to tell if they are a carrier for
a disease or not?
There is no way of telling this until we have a marker.
don't want to provide DNA because I am scared that my dog will be identified
as having the disease?
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.
we know anything about the status of the litter-mates of a dog affected
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.
there is a repeat mating where the first litter were all unaffected, would
the second litter also be clear?
the dogs still scratch and have pain after surgery?
How long it is before an improvement is seen?
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 as favourable.
are the risks of surgery?
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
post surgery drug treatment would you advise?
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).
prednisolone have to be continued after surgery?
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
if a group of breeders wanted to get their breeding dogs MRI scanned before
How would they go about it?
Who should they approach?
Where are the scanners?
Could a special price be negotiated?
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).
early could you MRI screen breeding stock?
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, 2½ years at the
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.|
The information given in these Research Updates are not necessariy those of the Cavalier King Charles Spaniel Club and are provided for information only
This document maintained by the firstname.lastname@example.org.
Material Copyright © 2005 The Cavalier King Charles Spaniel Cluband C Rusbridge