The Veterinary Journal 183 (2010) 345–347

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The Veterinary Journal

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Short Communication

Heritability of syringomyelia in Cavalier King Charles spaniels

Tom Lewis a,*, Clare Rusbridge b, Penny Knowler b, Sarah Blott a, John A. Woolliams c

a Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, UKb Stone Lion Veterinary Hospital, Wimbledon, London SW19 5AW, UKc Roslin Institute, Royal (Dick) School of Veterinary Studies, University of Edinburgh, Roslin, Midlothian EH25 9PS, UK

a r t i c l e i n f o a b s t r a c t

Article history:Accepted 20 October 2009

Keywords:SyringomyeliaCanineHeritabilityBreeding valueEstimated breeding valueCavalier King Charles spaniel

1090-0233/$ - see front matter � 2009 Elsevier Ltd. Adoi:10.1016/j.tvjl.2009.10.022

* Corresponding author. Tel.: +44 1638 751000; faxE-mail address: tom.lewis@aht.org.uk (T. Lewis).

Mixed model analysis of 384 Cavalier King Charles spaniels (CKCS), with a magnetic resonance imagingdiagnosis for the presence or absence of a syrinx, in conjunction with the Kennel Club pedigree records ofall dogs registered from the mid 1980s to September 2007, revealed a moderately high estimate of her-itability of syringomyelia (h2 = 0.37 ± 0.15 standard error) when analysed as a binary trait. Inspection ofcases where the disease segregated within families pointed to genes at more than one locus influencingsyringomyelia. The availability of estimated breeding values for Kennel Club registered CKCS is a signif-icant step in being able to select against syringomyelia, particularly given the difficulty of ascertainingthe disease phenotype.

� 2009 Elsevier Ltd. All rights reserved.

Introduction

Syringomyelia is a neurological condition that is relatively com-mon in the Cavalier King Charles spaniel (CKCS) and has been atthe forefront of the current debate about breeding practices andpedigree dogs in the UK (Higgins and Nichols, 2008). The conditionis characterised by the development of one or more fluid-contain-ing cavities (syringes) within the parenchyma of the spinal corddue to abnormal flow of cerebrospinal fluid (Rusbridge et al.,2006). This is often attributed to a Chiari-like malformation(CLM) and is believed to be endemic in the CKCS (Cross et al.,2009).

Clinical signs in CKCS with syringomyelia are dependent on thewidth and location of the syrinx and can include scratching, spon-taneous vocalisation after sudden postural change, scoliosis, tho-racic and/or pelvic limb ataxia and weakness. However, manydogs with a magnetic resonance imaging (MRI) diagnosis of syrin-gomyelia display no clinical signs (Lu et al., 2003; Couturier et al.,2008; Cerda-Gonzalez et al., 2009).

Syringomyelia is thought to be genetic in origin and this hascontributed to debate as to how to reduce the prevalence of thecondition in the CKCS (Rusbridge and Knowler, 2003, 2004). Thereare no accurate estimates of the prevalence of syringomyelia inCKCS in the UK, primarily due to the difficulty of definitive diagno-sis, which requires an MRI scan. The paucity of scanning data onhealthy CKCS leads to inaccurate estimation of the number of true

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negative diagnoses and an ascertainment bias in the data. Further-more, there are few estimates of the proportion of false negativediagnoses in dogs without an MRI scan, although Couturier et al.(2008) reported that 7/16 dogs without clinical signs had a syrinxupon scanning. The aim of this study was to estimate the heritabil-ity and calculate the estimated breeding values (EBV) of syringo-myelia in CKCS.

A single MRI diagnosis of syringomyelia status (affected/clear)of 384 Kennel Club registered CKCS was obtained from scans con-ducted from 1998 to 2009 by the authors or from MRI results sub-mitted to the Animal Health Trust by CKCS owners. Data wereexamined for scan records on multiple family members in an at-tempt to infer more information about modes of inheritance. Sta-tistical analysis fitting a mixed linear model was undertakenusing ASREML (Gilmour et al., 2006) to estimate genetic and envi-ronmental variance of development of syringomyelia (details sup-plied in Supplementary Material).

Three families were identified with an MRI diagnosis for bothparents and at least one progeny. In two families, both sire anddam were diagnosed with syringomyelia, but had progeny thatwere clear (at 3 years 6 months and 2 years 2 months of age),which appears to rule out syringomyelia being caused by an auto-somal recessive allele at a single locus. An extended family wherethe parents were clear on scanning at >3 years, but with many off-spring with a diagnosis of syringomyelia (61 year 3 months)(Fig. 1), appears to rule out syringomyelia being caused by an auto-somal dominant allele at a single locus. The lack of clear Mendeliansegregation within families suggests that syringomyelia is poly-genic or complex in origin. These conclusions are based on the

Fig. 1. Family tree showing syringomyelia segregating within full sib families and offspring affected by syringomyelia from apparently healthy parents. Grey indicatesunknown disease status; black indicates syringomyelia diagnosed by MRI; white indicates clear (negative) diagnosis from MRI scan; circle indicates female; square indicatesmale. The male dog scanned clear at 3 years 7 months, the female on the left scanned clear at 3 years 5 months and the female on the right scanned clear at 4 years 9 months.Such an occurrence would rule out an autosomal dominant mode of inheritance for a single gene.

346 T. Lewis et al. / The Veterinary Journal 183 (2010) 345–347

assumption of complete penetrance at age of scanning, which can-not be guaranteed.

The heritability of syringomyelia was 0.37 (±0.15 standard er-ror), indicating a moderate genetic effect on susceptibility to devel-opment of syringomyelia. There was a significant effect of bothyear of birth (P < 0.001) and age (P < 0.01) on development ofsyringomyelia (Fig. 2). A trend of decreasing age at scanning isillustrated by the broadly diagonal pattern of cells (showing datadistribution) and the pattern of shading indicates that earlier scan-ning years tended to yield more syringomyelia cases. There was nosignificant association of syringomyelia with coat colour.

EBVs for transmissible genetic susceptibility to syringomyeliawere calculated for all animals in the Kennel Club CKCS pedigreedatabase (n = 333,287; mean 0.0019 units ± 0.0331 standard devi-ation; co-efficient of skew �1.0123). Fig. 3 shows the mean EBVsfor all Kennel Club registered dogs from 1990 to 2006 (where dateof birth was recorded) in relation to year of birth and number bornper year and indicates a possible improving trend, but which issubject to the ascertainment bias.

Although this study presents strong evidence to suggest thatsyringomyelia in the CKCS is a disease with a genetic basis, it doesnot appear to be a single deleterious mutation that may have orig-inated by chance and drifted to a significant frequency, aided bythe low effective population size of the breed. It therefore remainspossible that syringomyelia is related to an aspect of the breeding

Age in yYear of birth 0 1 2 3 4

1991 1992 1993 1994 ### 1995 1996 ### 1997 ### ### 1998 ### ### ### 1999 ### ### ### 2000 ### ### ### 2001 ### ### ### ### 2002 ### ### ### ### ### 2003 ### ### ### ### ### 2004 ### ### ### ### ### 2005 ### ### ### ### 2006 ### ### ### 2007 ### ###

Fig. 2. Heat map showing predicted probabilities of syringomyelia for year of bir

objectives for the CKCS, such as skull morphology, but this cannotbe resolved without further quantitative studies.

Limitations of the present study include the small size of thedatabase and, as one collected for presence of disease, the likeli-hood of biased estimates arising from a lack of random sampling.Such biases are particularly problematic when the database iscompiled over the period during which the disease emerges. Thetransition to routine screening could explain the effects of year ofbirth and age of scanning shown in Fig. 2. The analysis used inthe present study was designed to minimise bias by includingthe interaction between year of birth and age at MRI scanning;however correction of bias requires collection of a random sampleto establish the true prevalence and the true degree of bias. Never-theless, the data used in the present study is based on the referencestandard (MRI) for diagnosis of the disease and clearly demon-strates the presence of genetic variation. The prevalence of syrin-gomyelia in CKCS is likely to be reduced by selection using EBVsif these are given sufficient priority to over-ride any positive selec-tion on the basis of conformation.

In conclusion, syringomyelia has a moderately high heritability(h2 = 0.37 ± 0.15 standard error) and thus selection against syringo-myelia should be feasible. The use of EBVs will assist in this aim,particularly since there is not an easily ascertained phenotype ordefinitive clinical signs. However, care must be taken in any pro-posed breeding programme to ensure that breeding away from

ears 5 6 7 8 9 10 11

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th related to age at scanning: Light grey < 0.2; dark grey 0.2–0.6; black > 0.6.

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Fig. 3. Mean and standard error of EBVs related to number of dogs born and registered with the Kennel Club per year from 1990 to 2006.

T. Lewis et al. / The Veterinary Journal 183 (2010) 345–347 347

syringomyelia does not result in a concomitant increase in otherdiseases, such as myxomatous mitral valve disease, or a substantialloss of genetic diversity.

Conflict of interest statement

None of the authors of this paper has a financial or personalrelationship with other people or organisations that could inappro-priately influence or bias the content of this paper.

Acknowledgements

This work was funded by the Kennel Club Charitable Trust. JAWis grateful to BBSRC for funding.

Appendix A. Supplementary material

Supplementary data associated with this article can be found, inthe online version, at doi:10.1016/j.tvjl.2009.10.022.

References

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