Identification of gene(s) prediposing to syringomyelia associated with Chiari-like malformation in the Cavalier King Charles Spaniel

Canine Chiari malformation is characterised overcrowding of the brain (too big) in the skull (too small) and hindbrain herniation. A consequence is obstruction of cerebrospinal fluid pathways and syringomyelia where fluid filled cavities develop in the spinal cord. The main consequence of Canine Chiari malformation and syringomyelia is (neuropathic) pain. The condition has similarities to human Chiari type I Malformation and studying the canine model offer opportunities to better understand the human condition.

Clinical work is centred at Fitzpatrick Referrals with facilities for MRI, CT, surgery and rehabilitation. Clare Rusbridge identified and described inherited canine Chiari-like malformation and syringomyelia in 1997 in Cavalier King Charles spaniels. Since then, working in partnership with dedicated breeders and pet owners worldwide, she has initiated many collaborative projects designed to improve our understanding of the phenotypical and genetic nature of Chiari malformation and syringomyelia.

We also focus on understanding the pathophysiology, bettering treatment and understanding the neurobehavioural effects of neuropathic pain. Most recent has been the identification of candidate genes for Chiari malformation in the Griffon Bruxellois.

Investigation of the genetic causes of Canine Chiari malformation by statistical genetic analysis of whole canine genome scans

• Dr Zoha Kibar and Dr Guy Rouleau, University of Montreal

Establishment of a large DNA collection of dogs affected with CMSM. This project would not be possible without the commitment and dedication of many dog owners

• Purebred toy dog breeders and pet owners, worldwide
• Margaret Carter and Tania Ledger, Cavalier Matters, UK
• Sandy Griffith, Stone Lion Goddard Vet Group, UK
• Mr Giunio Bruto Cherubini, University of Nottingham
• Erik Noorman- Dierenkliniek den Heuvel, Netherlands
• Dr Paul Mandigers, Utrecht University, Netherlands
• Dr Georgina Child, Sydney, Australia

Investigation of systemic fibrosis and other pathological and neurochemical changes associated with canine Chiari malformation and syringomyelia

• Dr Penny Watson and Dr Fernando Constantino-Casas, University of Cambridge

Multicentre collaboration allowing knowledge and data to be pooled and we are appreciative to have been involved with many initiatives from the

• Dr Holger Volk, Royal Veterinary College

The effect of neuropathic pain on neurobiology and behavior in collaboration

• Prof Mike Mendl and Dr Jo Murrell, Bristol University

Developmental and Conformational Indicators for Chiari malformation and Syringomyelia

• Thomas Mitchell, Bristol University
• Jane Sykes, Lawson Health Research Institute, Canada
• Lee Pieterse, Australia
• Henny van der Berg, Netherlands

Chiari malformation and syringomyelia in the Chihuahua

• Dr Tarja Jokinen and Dr Anna-Mariam Mappi, University of Helsinki

References

• Quantitative Trait Loci (QTL) Study Identifies Novel Genomic Regions Associated to Chiari-Like Malformation in Griffon Bruxellois Dogs P Lemay, SP Knowler, S Bouasker, Y Nédélec, S Platt, C Freeman, G. Child, L. B Barreiro, G A Rouleau, C Rusbridge, Z Kibar PloS one 9 (4), e89816
• Quantitative Analysis of Chiari-Like Malformation and Syringomyelia in the Griffon Bruxellois Dog SP Knowler, AK McFadyen, C Freeman, M Kent, SR Platt, Z Kibar, C Rusbridge. PloS one 9 (2), e88120
• Chiari–like malformation and syringomyelia C Rusbridge European Journal Companion Animal Practice 23, 70-89
• An update on the pathogenesis of syringomyelia secondary to Chiari-like malformations in dogs CJ Driver, HA Volk, C Rusbridge, LM Van Ham The Veterinary Journal, 2013 1–9. doi:10.1016/j.tvjl.2013.07.014
• Progression of otitis media with effusion in the Cavalier King Charles spaniel SJ McGuinness, EJ Friend, SP Knowler, ND Jeffery, C Rusbridge Veterinary Record 2013 172 (12), 315-315
• Caudal cranial fossa partitioning in Cavalier King Charles spaniels TA Shaw, IM McGonnell, CJ Driver, C Rusbridge, HA Volk Veterinary Record 2013 172 (13), 341-341
• Changes over time in craniocerebral morphology and syringomyelia in cavalier King Charles spaniels with Chiari-like malformation CJ Driver, L De Risio, S Hamilton, C Rusbridge, R Dennis, IM McGonnell, HA Volk BMC veterinary research 2013 8 (1), 1-7
• Long-term outcome of Cavalier King Charles spaniel dogs with clinical signs associated with Chiari-like malformation and syringomyelia. Plessas IN, Rusbridge C, Driver CJ, Chandler KE, Craig A, McGonnell IM, Brodbelt DC, Volk HA. Vet Rec. 2012 Nov 17;171(20):501. doi: 10.1136/vr.100449. Epub 2012 Oct 25.
• Questionnaire-based behaviour analysis of Cavalier King Charles spaniels with neuropathic pain due to Chiari-like malformation and syringomyelia. Rutherford L, Wessmann A, Rusbridge C, McGonnell IM, Abeyesinghe S, Burn C, Volk HA. Vet Journal. 2012 194 (3), 294-298.
• Increase in Cerebellar Volume in Cavalier King Charles Spaniels with Chiari-like Malformation and Its Role in the Development of Syringomyelia. Shaw TA, McGonnell IM, Driver CJ, Rusbridge C, Volk HA. PLoS One. 2012;7(4):e33660. Epub 2012 Apr 10.
• Effectiveness of breeding guidelines for reducing the prevalence of syringomyelia. Knowler SP, McFadyen AK, Rusbridge C. Vet Rec. 2011 Dec 24-31;169(26):681. Epub 2011 Oct 13.
• Distribution of substance P and calcitonin gene-related peptide in the spinal cord of Cavalier King Charles Spaniels affected by symptomatic syringomyelia. Hu HZ, Rusbridge C, Constantino-Casas F, Jeffery N. Res Vet Sci. 2012  93 (1), 318-320
• Histopathological Investigation of Syringomyelia in the Cavalier King Charles Spaniel, Hu H. Z, Rusbridge C, Constantino-Casas F, Jeffery ND, J Comp Pathol. 2012 Feb;146(2-3):192-201
• Prevalence of asymptomatic syringomyelia in Cavalier King Charles spaniels. Parker JE, Knowler SP, Rusbridge C†, Noorman E, Jeffery ND. Veterinary Record. 2011 Jun 25;168(25):667
• Distribution of syringomyelia along the entire spinal cord in clinically affected Cavalier King Charles Spaniels. Loderstedt S, Benigni L, Chandler K, Cardwell JM, Rusbridge C, Lamb CR, Volk HA. Vet J. 2011 Jan 7
• Morphometric assessment of cranial volumes in age-matched Cavalier King Charles spaniels with and without syringomyelia. Driver CJ, Rusbridge C, McGonnell IM, Volk HA Vet Rec. 2010 Dec 18;167(25):978-9.
• Relationship of brain parenchyma within the caudal cranial fossa and ventricle size to syringomyelia in cavalier King Charles spaniels Driver C. J., Rusbridge C., Cross H. R., McGonnell I. Volk  H. A. Journal of Small Animal Practice 2010, 51, 382-386.
• Heritability of syringomyelia in Cavalier King Charles spaniels. Lewis T, Rusbridge C, Knowler P, Blott S, Woolliams JA. Vet J. Vet J. 2010 Mar;183(3):345-7
• Chiari-like malformation--syringomyelia in the Cavalier King Charles Spaniel Mandigers P, Rusbridge C.  Tijdschr Diergeneeskd. 2009 Sep 15;134(18):746-50
• Chiari-like malformation in the Griffon Bruxellois Rusbridge C., Knowler S. P., Pieterse L, McFadyen A. K. Journal of Small Animal Practice 2009 50 (8): 386-393
• Association between cervical and intracranial dimensions and syringomyelia in the cavalier King Charles spaniel Carruthers H., Rusbridge C, Dubé M.-P., Holmes  M. Jeffery  N. Journal of Small Animal Practice 2009 50 (8): 394-398
• Comparison of cerebral cranium volumes between cavalier King Charles spaniels with Chiari-like malformation, small breed dogs and Labradors Cross H. R., Cappello R., Rusbridge C,.  Journal of Small Animal Practice 2009 50 (8): 399-405
• Radiographic morphology of the cranial portion of the cervical vertebral column in Cavalier King Charles Spaniels and its relationship to syringomyelia. Stalin CE, Rusbridge C, Granger N, Jeffery ND. Am J Vet Res. 2008 Jan;69(1):89-93.
• Chiari-like malformation with syringomyelia in the Cavalier King Charles spaniel: long-term outcome after surgical management Rusbridge C. Vet Surg. 2007 Jul;36(5):396-405.
• Syringomyelia in cavalier King Charles spaniels: the relationship between syrinx dimensions and pain. Rusbridge C, Carruthers H, Dubé MP, Holmes M, Jeffery ND. J Small Anim Pract. 2007 Aug;48(8):432-6. Epub 2007 Jun 30.
• Report from the Chiari‐Like Malformation and Syringomyelia Working Group Round Table R Cappello, C Rusbridge Veterinary Surgery 36 (5), 509-512
• Pathophysiology and treatment of neuropathic pain associated with syringomyelia. Rusbridge C, Jeffery ND. Vet J. 2008 Feb;175(2):164-72. Epub 2007 Feb 20.
• Coexistence of occipital dysplasia and occipital hypoplasia/syringomyelia in the cavalier King Charles spaniel. Rusbridge C, Knowler SP. J Small Anim Pract. 2006 Oct;47(10):603-6.
• Syringomyelia: current concepts in pathogenesis, diagnosis, and treatment. Rusbridge C, Greitz D, Iskandar BJ. J Vet Intern Med. 2006 May-Jun;20(3):469-79
• Neurological diseases of the Cavalier King Charles spaniel Rusbridge C. J Small Anim Pract. 2005 Jun;46(6):265-72.
• Inherited occipital hypoplasia/syringomyelia in the cavalier King Charles spaniel: experiences in setting up a worldwide DNA collection Rusbridge C. Knowler P, Rouleau GA, Minassian BA, Rothuizen J. J Hered. 2005;96(7):745-9. Epub 2005 Jun 15.
• Inheritance of occipital bone hypoplasia (Chiari type I malformation) in Cavalier King Charles Spaniels. Rusbridge C#, Knowler SP J Vet Intern Med. 2004 Sep-Oct;18(5):673-8.
• Hereditary aspects of occipital bone hypoplasia and syringomyelia (Chiari type I malformation) in cavalier King Charles spaniels. Rusbridge C, Knowler SP † Vet Rec. 2003 Jul 26;153(4):107-12.
• Dorsal dens angulation and a Chiari type malformation in a Cavalier King Charles Spaniel. Bynevelt M, Rusbridge C, Britton J. Vet Radiol Ultrasound. 2000 Nov-Dec;41(6):521-4.
• Syringohydromyelia in Cavalier King Charles spaniels. Rusbridge C ,MacSweeny JE, Davies JV, Chandler K, Fitzmaurice SN, Dennis R, Cappello R, Wheeler SJ. J Am Anim Hosp Assoc. 2000 Jan-Feb;36(1):34-41.