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Syringomyelia (SM) Breeding Protocol

CavalierHealth.org Copyright © 2004 Blenheim CompanyDr. Clare Rusbridge, BVMs, DipECVN, MRCVS, PhD., of the Stone Lion Veterinary Centre in Wimbledon, UK, published the following breeding guidelines in January 2007, for Cavalier King Charles Spaniel breeders to follow to try to avoid the worst aspects of Syringomyelia (SM) in future generations of Cavaliers.

Dr. Rusbridge and Susan P. (Penny) Knowler, BSc (Hons), have been conducting an extensive study of syringomyelia and the Cavalier King Charles Spaniel for several years, and they published their first recommended breeding guidelines for SM in January 2004.

In November 2006, at an international syringomyelia conference sponsored by the U.K. Cavalier King Charles Spaniel Club's research fund, the attending neurologists and other specialists from five countries conferred at the Royal Veterinary College in Hertfordshire to discuss revisions to the previously published versions of Dr. Rusbridge's SM breeding protocol.  A result of that conference is this November 2006 protocol, the fourth version.

This SM Breeding Protocol is not universally accepted by neurologists researching Chiari-like malformation (CM) and SM in the CKCS.  Most significantly, George C. Skerritt, BVSc, MIBiol ,CBiol, DipECVN, FRCVS, of the ChesterGates Animal Referral Hospital in Chester, UK wrote in April 2008 that "I must comment on the breeding scheme recommended by Claire Rusbridge. In my opinion it is not nearly strict enough; it advocates the breeding of affected dogs – I fail to see the value of a scheme that actively perpetuates the very condition that it seeks to eliminate."

Dr. Rusbridge's and Ms. Knowler's third version of the protocol, which they published in August 2005, follows this presentation of the new, November 2006 third version, for comparison purposes. A major difference between the two versions is that the presence or absence of the Chiari-like malformation (CM) was dropped from the November 2006 breeding guidelines because of: (a) the ubiquity of the malformation within the CKCS population; (b) the lack of uniformity between veterinarians recognizing and consistently grading the severity of CM; and (c) the lack of evidence that the apparent severity of CM was related to severity of syringomyelia.


Rusbridge Syringomyelia Breeding Recommendations (November 2006)
by Clare Rusbridge, BVMS DipECVN MRCVS PhD

Introduction

Dr. Clare Rusbridge 2006 CavalierHealth.org -- Blenheim CompanyThe diagnosis of syringomyelia is easily confirmed by MRI but neurologists have yet to define what is meant by the term 'clear' given that most cavaliers have a degree of skull malformation. The late onset of clinical signs and the number of asymptomatic dogs adds to the complexity of the condition. Not enough is known about long term progression to ascertain the optimum age young dogs should be screened for the disease. The research is an evolving process and hopefully a proven accurate and UNIVERSAL scheme will be developed eventually. Recent studies suggests that in the vast majority of cases the syrinx starts in the upper cervical spinal cord so if this is included then scanning of the entire cord (more expensive) may not ultimately be necessary. Any 'normal' dog without the occipital malformation which makes the skull small has a genetic advantage and should be used for breeding.

The following breeding recommendations are made using current information and in response to breeder requests for guidelines. It has yet to be proven if this guide is appropriate. The aim of these recommendations is to reduce the incidence of symptomatic syringomyelia in the breed not to create litters of puppies guaranteed not to have SM as the chance of producing an affected dog cannot be predicted without knowing the inheritance. It is recommended that the offspring of any mating is also MRI screened before breeding. As the incidence of syringomyelia is so high in the breed there will be severe depletion of the gene pool if only clear dogs are used (i.e. other problems will develop). Therefore until the genetic defect is determined it is recommended that dogs with syringomyelia be used if they are valuable in another genetic sense e.g. good heart. The general principle of these guidelines is that dogs with code A are more desirable to use than B, etc but that dogs with a higher letter code may still be used in some limited circumstances.


International Syringomyelia Conference November 2006
Revised CKCS MRI screening and breeding recommendations

These breeding recommendations are made using current information and in response to CKCS breeder request for guidelines. It has yet to be proven if this guide is appropriate. The aim of these recommendations is to reduce the incidence of symptomatic syringomyelia (SM) in the breed not to create litters of puppies guaranteed not to have SM as the chance of producing an affected dog cannot be predicted without knowing the inheritance.

Note- The age cut off at 2.5 years has been decided so as to tie in with MVD recommendations and because most dogs with symptomatic SM will show signs before 3 years of age.

The following categories from the previous guidelines [See August 2005 SM Breeding Recommendations, below] have been removed because of difficulty in accurately interpreting:

Previously A * - now A
Previously B - now C

It is recommended:

1. That both the sire and the dam of a proposed mating are screened (any unscreened dog should be assumed to be "D")

2. Offspring of any mating should also be MRI screened before breeding.

3. Any dog screened before 2.5 years old has a second screen when older.

4. That dogs are screened from 6 months of age.

5. That if a limited ("mini" ) MRI screen is performed that:

(a) the minimum area covered is from approximately the level of the thalamus / corpus callosum to cervical vertebrae 5 (C5).

(b) Both TW1 and TW2 = sagittal images are obtained in addition to TW1 and /or TW2 transverse images through the upper cervical spinal cord.

(c) An assessment is also made for presence/absence of ear disease and ventricular enlargement.

6. That interpretation of images is made by Diplomate level radiologists, neurologists and, in special circumstances, by orthopedic surgeons with recognized expertise in this area. 

Color code: red = under 2.5 years; blue = over 2.5 years; purple = any age

CODE AGE (yrs) SYRINGOMYELIA BREED TO

 A

Over 2.5


Absent or less than 2mm central canal dilatation in the C2-C4 region only
A, C, D
C Under 2.5 Absent
A (Re-scan after 2.5 years)
D Over 2.5 Present but asymptomatic
A
E Under 2.5 Present but asymptomatic
SHOULD NOT BE BRED
F Any Present and symptomatic
SHOULD NOT BE BRED

August 2005 Version of the Syringomyelia Breeding Protocol

The following is the August 2005 protocol by Dr. Rusbridge and Ms. Knowler. As their research has progressed and their knowledge of the disease has increased, they have modified their earlier recommendations.

What follows, first, is their verbatim August 2005 Syringomyelia Breeding Protocol, followed by the CavalierHealth.org editor's analysis of their breeding recommendations. To best understand the terminology which they use, the reader first should read Syringomyelia In Depth. All Cavalier fanciers should be deeply indebted to these SM researchers and their counterparts worldwide for the effort they have put into assisting CKCS breeders in taking measures to reduce the incidence of SM in future generations of the breed. Of course, it is completely up to the breeders as to whether they will pay any attention at all to these guidelines.


Rusbridge/Knowler Syringomyelia Breeding Recommendations
(August 2005)

by Dr. Clare Rusbridge and Susan P. (Penny) Knowler

The diagnosis of syringomyelia is easily confirmed by magnetic resonance imaging (MRI), but neurologists have yet to define what is meant by the term “clear”, given that most Cavaliers have a degree of skull malformation. The late onset of clinical signs and the number of asymptomatic dogs adds to the complexity of the disease. Not enough is known about long term progression to ascertain the optimum age young dogs should be screened for the disease. The research is an evolving process, and hopefully a proven accurate and UNIVERSAL scheme will be developed eventually. Recent studies suggest that in the vast majority of cases, the syrinx starts in the upper cervical spinal cord, so if this is included, then MRI scanning of the entire spinal cord (more expensive) may not ultimately be necessary. Any “normal” dog, without the occipital malformation which makes the skull small, has a genetic advantage and should be used for breeding.

The following breeding recommendations are made using current information and in response to breeder requests for guidelines. It has yet to be proven if this guide is appropriate. The aim of these recommendations is to reduce the incidence of symptomatic syringomyelia in the breed -- not to create litters of puppies guaranteed not to have SM -- as the chance of producing an affected dog cannot be predicted without knowing the inheritance. It is recommended that the offspring of any mating is also MRI screened before breeding. As the incidence of syringomyelia is so high in the breed, there will be severe depletion of the gene pool if only clear dogs are used (i.e. other problems will develop). Therefore, until the genetic defect is determined, it is recommended that dogs with syringomyelia be used if they are valuable in another genetic sense (e.g. good heart). The general principle of these guidelines is that dogs with Grade A are more desirable to use than those with Grade B, etc., but that dogs with a higher letter Grade may still be used in some limited circumstances.

Notes: The age cut off at 2.5 years has been decided so as to tie in with MVD recommendations and because most dogs with symptomatic syringomyelia will show signs before 3 years of age. These recommendations will only work if the Cavaliers are actually MRI scanned!! Any dog not MRI scanned is assumed to be Grade D or E depending on its age. Dogs may develop signs of syringomyelia at any age, e.g., a dog can be free of pain until 7 years old, i.e. , a dog’s status may change as it gets older.

GRADE AGE (YEARS)  (see footnote 3) SYRINGOMYELIA OCCIPITAL HYPOPLASIA MITRAL VALVE DISEASE (MVD) (see footnote 1) BREED TO
A* Any age Absent Absent Fail/Pass  Grades A, B, C, D
A Older than 2.5 Absent or central canal dilatation in the C2-C4 region only Present (see footnote 2) Pass Grades A, B, C, D
B Younger than 2.5 Absent Mild (see footnote 2) Dam & Sire Pass Grades A, B, C, D. Consider rescan after 2.5 years to clarify status, monitor heart
C Younger than 2.5 Absent Present (see footnote 2) Dam & Sire Pass Grades A, B. Consider rescan after 2.5 years to clarify status, monitor heart
D
(see footnote 4)
Older than 2.5 Present but Asymptomatic Present (see footnote 2) Pass Grades A, B
E
(see footnotes
4 & 5)
Younger than 2.5 Present but Asymptomatic Present (see footnote 2) Dam & Sire Pass Wait until 2.5 years to clarify status
F Older than 2.5 Present but Asymptomatic Present (see footnote 2) Fail NO
F Any age Present and Symptomatic Present (see footnote 2) Fail/Pass NO

Footnotes to Table:

1. MVD - to "Pass", a Cavalier must be free of systolic murmur over 2.5 years old with systolic murmur-free parents over 5 years old. [Editor's Note: This is the MVD Breeding Protocol.]

2. Occipital hypoplasia can be difficult to define because, in comparison to other toy breeds, the back of the CKCS's skull is smaller – i.e.‚ a "normal" Cavalier skull is very hard to find, and there are few CKCS that meet Code A+. In addition, the term "too small" has not been defined; nor is there a consensus as how to measure the occipital bone. Basically, there are three classic features of occipital malformation: (1) loss of the normal round shape of the cerebellum, which can appear indented by the occipital bone; (2) displacement of the cerebellum into and through the foramen magnum, i.e., herniation; and (3) kinking of the medulla. Mild occipital hypoplasia is defined as a displacement of the cerebellum into the area of the foramen magnum and slight kinking of medulla and indentation of the cerebellum (see diagrams below).

CavalierHealth.org -- Blenheim CompanyMild occipital hypoplasia – [Right] The cerebellum is very slightly indented. The kinking of the medulla is normal for a toy breed, and there is displacement of the cerebellum into and just out of the foramen magnum. The ventricular system is slightly dilated. This dog is Grade B. If he was older than 2.5 years, he would be Grade A.

CavalierHealth.org -- Blenheim CompanyAlthough the cerebellum is not coming through the foramen magnum, this dog [Right] has a greater degree of occipital hypoplasia than the dog above. See how the cerebellum is indented and the medulla is kinked. The central canal is dilated above the first disc space – this is the first sign of syringomyelia developing. There is also mild ventricular dilatation. This dog would be Grade C if less than 2.5 years.

CavalierHealth.org -- Blenheim CompanyThis dog [Right] has descent of the cerebellum towards the foramen magnum and the cerebellum is indented. The medulla is normal for a toy breed; there is mild ventricular dilatation and a small syrinx/central canal dilatation in the upper cervical spinal cord. However he is 8 years old with a clear heart. He is Grade A. 3. Dogs may develop signs of syringomyelia at any age, e.g., a dog can be free of pain until 7 years old. Therefore, a dog’s status may change as it gets older.

4. Any dog not MRI scanned is assumed to be no better than Grade D or E, depending upon its age.

5. Breed clubs should consider whether to recommend that stud dogs are MRI scanned. Males have most influence on the gene pool (popular champions sire hundreds) and by the time it is known that a dog may pass on the tendency, his genes may be widespread. It would be sensible that if a male dog is to be used more than twice, then, for the safety of the breed, he should be Grade A or B. It would perhaps be a good use of research funds to use them to subsidize the testing of stud dogs and publish a clear list. A salient fact is that 93% of the top stud dogs in the UK are closely related to one or more dogs with SM, and the pedigrees of these dogs are similar to champions worldwide.


Editor's Analysis of Rusbridge/Knowler August 2005
Syringomyelia Breeding Recommendations

The latest version of the syringomyelia (SM) breeding protocol raises several significant points:

First, all grades of Cavaliers to be bred under this protocol (Grades A*, A, B, C, and D) should have been examined by an MRI scan. Under previous SM protocols, Rusbridge/Knowler expressly allowed for breeding certain CKCSs which had not been scanned. They state here that any un-scanned Cavalier is to be graded D or E, depending upon its age.

The ideal candidate for breeding is graded A*, which is a Cavalier which qualifies under the mitral valve disease (MVD) breeding protocol and has neither SM nor occipital hypoplasia. A Grade A* Cavalier may be bred to any of the lower grade dogs, A, B, C, and/or D.

It is obvious that Rusbridge/Knowler do not believe that there will be enough breedable Cavaliers which are Grade A*, because they then list lower grades (A, B, C, and D), all of which either have occipital hypoplasia with no SM or even have mild forms of SM.

Despite all CKCSs having MRIs, Rusbridge/Knowler's second category, Grade A, allows for the breeding of Cavaliers which have been diagnosed with both occipital hypoplasia and a mild case of SM. Grade A dogs are over age 2.5 and have satisfied the MVD breeding protocol but which may have a form of SM, central canal dilatation of the spinal cord, in the C2-C4 region of the spine. These Grade A Cavaliers may be bred to Grade A, B, C, and/or D dogs.

Rusbridge/Knowler's third level of eligible CKSCs are those under age 2.5 years and diagnosed with occipital hypoplasia but no SM. These are dogs graded B (mild occipital malformation) or C (the malformation is "present"). Significantly, the breeding of CKCSs in this category would violate the MVD breeding protocol, since that protocol forbids breeding any Cavalier under age 2.5 years. Rusbridge/Knowler temper their recommendation of breeding a Grade B or C dog by requiring that the both of the dog's parents meet the MVD protocol by being MVD-murmur clear at age 5 years. So, under the Grade B and C categories, if the breeding dog's parents satisfy the MVD protocol, it may be bred even though it is under age 2.5 years.

The Grade B Cavalier, which has only mild occipital hypoplasia, may be bred to any grade of Cavalier: A, B, C, and/or D. The Grade C Cavalier, with occipital hypoplasia "present" (and presumably more severe than just "mild") may be bred only to Grade A or B dogs. Rusbridge/Knowler recommend that both Grade B and C Cavaliers be re-scanned with MRI after age 2.5 years, and that the MVD status continue to be monitored.

Rusbridge/Knowler do not appear to explain why they believe it appropriate to breed any Cavalier under age 2.5 years. The MVD breeding protocol is emphatic that no CKCS be bred under age 2.5 years, so as to reduce the incidence of early-onset MVD. Perhaps Rusbridge/Knowler have weighed the risk of perpetuating early-onset MVD against any onset of SM. Granted, even these underaged CKCSs must have parents which had clear hearts at age 5 years. So, they are heeding some aspects of the MVD protocol. But they still do not appear to answer the obvious questions: Why not wait until the Grade B and C breeding stock is 2.5 years old and MVD murmur-free? What is their scientific basis for the rush?

These underaged Grade B and C Cavaliers clearly are not ideal candidates for breeding, because, as Rusbridge/Knowler note in their recommendations, the first MRI evidence of SM may not show up until age 2.5 years or older.

Their next category of breedable Cavalier, Grade D, is over age 2.5 years, meets the MVD protocol, but has both the occipital malformation and asymptomatic SM (SM without any symptoms).

Finally, they list two categories of non-breedable Cavaliers, Grades E and F. A Grade E dog is under age 2.5 years, with parents who meet the MVD protocol, but which has both the malformation and asymptomatic SM. Instead of breeding the underaged Grade E Cavalier now, they recommend waiting until it is over 2.5 years. Presumably then, if it passes the MVD protocol, it will become a breedable Grade D, and if it fails the MVD test, it will be a non-breedable Grade F.

The Grade F Cavalier can be in either of two sub-categories. Neither makes it breedable. It can be over age 2.5 and not meet the MVD protocol, with both the occipital malformation and asymptomatic SM. Or it can be of any age, either pass or fail the MVD protocol, and have symptomatic SM.

As for the vast majority of Cavaliers, those which are un-scanned, Rusbridge/Knowler grade them either D or E, depending upon their ages. Of course, an un-scanned Cavalier with symptomatic SM would have to be Grade F, although Rusbridge/Knowler do not expressly say that.

In conclusion, Rusbridge/Knowler's August 2005 SM breeding recommendations align tightly, although not exclusively, with the MVD breeding protocol. In two instances, Grades B and C, they allow for underaged Cavaliers to be bred, but they require the parents to pass the MVD protocol (meaning be murmur-clear at age 5 years), and they advise that the Cavaliers' hearts be monitored and re-examined after age 2.5 years. All in all, the August 2005 Rusbridge/Knowler SM breeding protocol is a refreshing and robust re-affirmation of the 1998 MVD breeding protocol. Let us hope that more CKCS breeders start paying heed to it, as well.


Related Links

Syringomyelia
Dr. Rusbridge's Website
Dr. Rusbridge's Doctoral Thesis
Dr. Rusbridge's Syringomyelia News Winter 2007 Research Update
Dr. Rusbridge's Syringomyelia News Autumn 2007 Research Update
Dr. Rusbridge's Syringomyelia News 2007 Research Update
Mitral Valve Disease Breeding Protocol
Questions for Cavalier Breeders
Board Certified Veterinary Neurologists
A SM support group is http://uk.groups.yahoo.com/group/ArnoldChiari_dogs/ 
A SM discussion group is http://groups.yahoo.com/group/CKCS-SM/
A website devoted to syringomyelia in Cavaliers is Karlin Lillington's SM.CavalierTalk.com

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