Curly Coat / Rough Coat Syndrome
and the Cavalier King Charles Spaniel
What It Is
A rarer but far more severe form of dry eye syndrome in some cavalier King Charles spaniel puppies is a combination of dry eye* and a congenital skin condition called "curly coat" or "rough coat" syndrome (ichthyosis keratoconjunctivitis sicca).
No cases of the combination of dry eye syndrome and curly coat syndrome have been reported in any other breed. Studies have been conducted in the United States, United Kingdom, Australia, Sweden, the Czech Republic, and Iceland. During a two year period recently in Iceland, more than half of many litters of cavalier puppies were born affected by the syndrome. The disorder may be more widespread than previously believed as more owners and veterinarians become aware of its symptoms.
It has been determined to be due to a simple autosomal recessive gene, a mutation of the FAM83H gene*. As a result, affected puppies are more likely to be found in cases of line breeding or inbreeding on carrier bloodlines.
* This was confirmed most recently in a 2011 report and a 2012 report.
Symptoms
The reference to a curly or rough coat comes from the unusually curly abnormality of the cavalier's coat which is apparent at birth. (See cavalier pup with curly coat syndrome at top right.) However, the puppy also suffers from an extreme version of dry eye, and as the affected dog matures, it develops a deterioration of the skin which results in seborrhea, consisting of skin inflammation and excessive oiliness. Also, the dog's teeth, gums, and other connective tissues may be adversely affected. The form of dry eye associated with curly coat also is distinctive in that it is of congenital origin.
In a 2011 report by UK researchers who have studied this disorder for many years, they describe the symptoms thusly:
"Cases presented with a congenitally abnormal (rough/curly) coat and signs of KCS [keratoconjunctivitis sicca] from eyelid opening. Persistent scale along the dorsal spine and flanks with a harsh frizzy and alopecic coat was evident in the first few months of life. Ventral abdominal skin was hyperpigmented and hyperkeratinized in adulthood. Footpads were hyperkeratinized from young adulthood with nail growth abnormalities and intermittent sloughing."
*Dry eye is a syndrome very common in cavaliers. Read about it here.
DNA Testing
The UK's Animal Health Trust offers a DNA swab test for the mutations causing dry eye/curly coat syndrome, through the AHT’s online DNA testing webshop. The DNA test is available world-wide. See Current Research below for more information about this syndrome.
Treatment
In cases of curly coat syndrome, nearly continuous daily care, including very frequent medicinal bathing, is required to treat the skin condition, as well as applying the eye medications. In a 2003 study reported by Dr. Keith C. Barnett, OBE MA PhD BSc DVOphthal FRCVS DIpECVO, European Specialist in Veterinary Ophthalmology, the dry eye condition of curly coat dogs may be so severe that cyclosporine therapy is ineffective, and the skin condition progresses into severe lesions. In a September 2006 paper, Dr. Barnett reported that successful treatment of the skin condition is not possible, although there can be some improvement in the dry eye condition.
In a 2011 research study, Dr. Barnett and others found that "lacrimostimulant treatment [e.g., cyclosporin] had no statistically significant effect on Schirmer tear test results, although subjectively, this treatment reduced progression of the keratitis [dry eye]."
Dr. Barnett also reported in his 2003 study that the need for constant care of the eyes and skin may lead breeders to resort to early euthanasia of the affected puppies as the only humane result, to avoid the dogs suffering from lifetimes of extreme discomfort and permanent eye damage.
Current Research
4January 2012: UK researchers identify mutated gene causing curly coat in the cavalier. Drs. Oliver P. Forman, Jacques Penderis, Claudia Hartley, Louisa J. Hayward, Sally L. Ricketts, and Cathryn S. Mellersh of the Animal Health Trust and University of Glasgow have identified a mutation of the FAM83H gene was associated with curly coat in the CKCS. See report below.
4December 2011: UK researchers find dry eye medications have mixed results. In a 2011 UK study of cavaliers suffering from both dry eye and curly coat syndrome, the researchers found that "lacrimostimulant treatment had no statistically significant effect on Schirmer tear test results, although subjectively, this treatment reduced progression of the keratitis [dry eye]."
4April 2011: Animal Health Trust Starts DNA Test for Curly Coat in Cavaliers. On April 18, 2011. Animal Health Trust (AHT) begins offering to cavalier breeders its DNA test to detect the mutations causing dry eye/curly coat syndrome, through the AHT’s online DNA testing webshop. The DNA test is available world-wide. Read more here.
4November 2010: DNA Region for Curly Coat Has Been Found. Animal Health Trust (AHT) veterinary geneticist Dr. Tom Lewis announced at the UK Cavalier Club's "Cavalier Health Day" on November 20 that the DNA region for the curly coat syndrome in cavaliers has been located. The AHT is continuing its research, started by the late Dr. Keith C. Barnett, to identify the precise mutations of gene(s) causing curly coat syndrome (ichthyosis keratoconjunctivitis sicca). The Trust's future plan is to offer a DNA test for the mutations to cavalier breeders.
4March 2009: Dr. Keith C. Barnett died on March 10, 2009.
4March 2007: The Animal Health Trust (AHT) is conducting research to try to establish the pattern of inheritance of CKCS puppies born with the combination of both dry eye and curly coat syndrome (ichthyosis keratoconjunctivitis sicca), which appears to be unique to the cavalier as a breed. According to Dr. Keith C. Barnett, OBE MA PhD BSc DVOphthal FRCVS DIpECVO, European Specialist in Veterinary Ophthalmology, who has been studying these conditions for several years, no cases of the two abnormalities occurring together have been recorded in any other breed.
Dr. Barnett and Dr. Cathryn Mellersh, BSc(hons) PhD, senior canine geneticist at the AHT, are leading a team of AHT colleagues who are researching the DNA of the puppies. Dr. Mellersh reports that twenty-seven candidate genes have been identified and the tests are currently in progress and final results are pending.
Dr. Barnett requests that breeders who have puppies affected with these combined disorders send blood samples and skin tissue samples from the affected puppies, their siblings, and parents to identify the responsible gene. Contact Dr. Barnett at the AHT if you wish to participate in the research project. He may be reached at Animal Health Trust, Lanwades Park, Kentford, Newmarket, CB8 7UU, United Kingdom; telephone: (+44) (0)8700 502424; email: Keith.Barnett@aht.org.uk Blood samples of 3 to 5 ml should be provided in ETDA anti-coagulant tubes. Alternatively, for very young or old donors, cheek swabs may be used. Samples should be marked for the attention of Dr. K. Barnett and sent to: Sarah Gray, The Animal Health Trust, Lanwades Park, Newmarket Suffolk CB8 7UU UK. Please indicate clearly that the samples are Curly Coat affected or related. Dr. Mellersh may be reached at Animal Health Trust, Lanwades Park, Kentford, Newmarket, Suffolk CB8 7UU, United Kingdom; telephone: (+44) (0)1638 750659 ; email: cathryn.mellersh@aht.org.uk
4January 2007: Drs. R. F. Sanchez (England), G. Innocent (Scotland), J. Mould (England), and F. M. Billson (Australia) reported in their January 2007 article, Canine keratoconjunctivitis sicca: disease trends in a review of 229 cases, in the Journal of Small Animal Practice, Volume 48, that the cavalier King Charles spaniels in their study "showed a more acute disease pattern with a biphasic age distribution at 0 to less than two years of age, and four to less than six and six to less than eight years of age, respectively, with more males affected than females and a significantly higher incidence of ulcerative keratitis in some cases resulting in corneal perforation."
Related Links
Dry Eye
Eyes
Questions for
Breeders
American College of Veterinary Ophthalmologists
Veterinary Resources
Dry eye and curly coat in the Cavalier King Charles Spaniel. Barnett, KC, Veterinary Ophthalmology 6 (4), 343-350, Dec. 2003.
Guide to Congenital and Heritable Disorders in Dogs. Dodds WJ, Hall S, Inks K, A.V.A.R., Jan 2004, Section II(179).
Breed Predispositions to Disease in Dogs & Cats. Alex Gough, Alison Thomas. 2004; Blackwell Publ. 44-45.
Ophthalmic Disease in Veterinary Medicine. Martin C.L. Manson Publ. 2005.
Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in the cavalier King Charles spaniel. K. C. Barnett. J.Sm.Anim.Prac. 2006 Sep;47(9):524-8. Quote: "Objectives: To record a previously unreported congenital and hereditary condition affecting the eyes and skin in the cavalier King Charles spaniel. ... In the cavalier King Charles spaniel, the coat abnormality was noted at birth by the breeders as a 'curly coat', with deterioration of the skin signs as the animal became adult."
Immunopathogenesis of Keratoconjunctivitis Sicca in the Dog. David L. Williams. Vet Clin Small Anim 38 (2008) 251–268.
Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (ckcsid) in the Cavalier King Charles Spaniel (CKCS) dog: a candidate gene study. C. Hartley, K. C. Barnett, C. S. Mellersh, L. Pettitt and O. P. Forman. Vet Ophthal (2009) 12(6):379–385. Quote: "Purpose: To identify causative mutation(s) for CKCSID in CKCS dogs using a candidate gene approach. Methods: DNA samples from 21 cases/parents were collected. Canine candidate genes (CCGs) for similar inherited human diseases were chosen. Twenty-eight candidate genes were identified by searching the Pubmed database (http://www.ncbi.nlm.nih.gov/sites/entrez/query.fcgi). Canine orthologs of human candidate genes were identified using the Ensembl orthologue prediction facility (http://www.ensembl.org/index.html). Two microsatellites flanking each candidate gene were selected and primers to amplify each microsatellite were designed using the Whitehead Institute primer design website (http://frodo.wi.mit.edu/cgibin/primer3/primer3_www.cgi). The microsatellites associated with all 28 CCGs were genotyped on a panel of 21 DNA samples from CKCS dogs (13 affected, 8 carriers). Genotyping data was analysed to identify markers homozygous in affected dogs and heterozygous in carriers (homozygosity mapping). Results: None of the microsatellites associated with 25 of the CCGs displayed an association with CKCSID in the 21 DNA samples tested. Three CCGs associated microsatellites were monomorphic across all samples tested. Conclusion: Twenty five CCGs were excluded as cause of CKCSID. Three CCGs could not be excluded from involvement in the inheritance of CKCSID."
Breed Predispositions to Disease in Dogs & Cats (2d Ed.). Alex Gough, Alison Thomas. 2010; Blackwell Publ. 51, 54.
New DNA tests for Cavalier King Charles spaniels. Vet Rec 2011 168(14):370. "NEW DNA tests to detect the mutations causing congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (dry eye and curly coat syndrome) and episodic falling in Cavalier King Charles spaniels will be available from the Animal Health Trust (AHT) later this month. Episodic falling is a neurological condition induced by exercise, excitement or frustration. The dog's muscle tone increases and the animal is unable to relax its muscles, becomes rigid and falls over. Dry eye and curly coat syndrome results in an affected dog producing no tears, so its eyes become sore. The skin becomes flaky and dry, particularly around the feet, which can make standing and walking difficult and painful. The syndrome appears to be unique to Cavalier King Charles spaniels and most dogs diagnosed with it are euthanased. Researchers at the Kennel Club Genetics Centre at the AHT have now identified the mutations responsible for the two conditions. This has allowed the development of the new DNA tests, which will be available from the AHT from April 18. Cathryn Mellersh, head of canine genetics at the AHT, said: To date there has been no long-term effective treatment for either dry eye and curly coat syndrome or episodic falling so the development of the DNA tests is an important breakthrough for breeders and owners of Cavalier King Charles spaniels. As with all inherited disease, it's important that breeders are armed with the facts and that they still continue to use carrier dogs in their breeding programmes. Breeding a carrier with a non-carrier will not produce affected puppies; however, breeding just clear dogs with other clear dogs could reduce the gene pool within the breed and this could lead to other health problems in the future."
Canine Inherited Disorders Database: http://www.upei.ca/~cidd/Diseases/ocular%20disorders/keratoconjunctivitis%20sicca%20.htm http://www.upei.ca/cidd/Diseases/dermatology/ichthyosis.htm
Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in 25 Cavalier King Charles spaniel dogs – part I: clinical signs, histopathology, and inheritance. Claudia Hartley, David Donaldson, Ken C. Smith, William Henley, Tom W. Lewis, Sarah Blott, Cathryn Mellersh, Keith C. Barnett. Vet.Opht. 29Dec2011. Quote: "The clinical presentation and progression (over 9 months to 13 years) of congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID) in the Cavalier King Charles spaniel dog are described for six new cases and six previously described cases. Cases presented with a congenitally abnormal (rough/curly) coat and signs of KCS from eyelid opening. Persistent scale along the dorsal spine and flanks with a harsh frizzy and alopecic coat was evident in the first few months of life. Ventral abdominal skin was hyperpigmented and hyperkeratinized in adulthood. Footpads were hyperkeratinized from young adulthood with nail growth abnormalities and intermittent sloughing. Long-term follow-up of cases (13/25) is described. Immuno-modulatory/lacrimostimulant treatment had no statistically significant effect on Schirmer tear test results, although subjectively, this treatment reduced progression of the keratitis. Histopathological analysis of samples (skin/footpads/ lacrimal glands/salivary glands) for three new cases was consistent with an ichthyosiform dermatosis, with no pathology of the salivary or lacrimal glands identified histologically. Pedigree analysis suggests the syndrome is inherited by an autosomal recessive mode."
Parallel Mapping and Simultaneous Sequencing Reveals Deletions in BCAN and FAM83H Associated with Discrete Inherited Disorders in a Domestic Dog Breed. Oliver P. Forman, Jacques Penderis, Claudia Hartley, Louisa J. Hayward, Sally L. Ricketts, and Cathryn S. Mellersh. PLoS Genet. 2012 January; 8(1): e1002462. Quote: "The domestic dog (Canis familiaris) segregates more naturally-occurring diseases and phenotypic variation than any other species and has become established as an unparalled model with which to study the genetics of inherited traits. We used a genome-wide association study (GWAS) and targeted resequencing of DNA from just five dogs to simultaneously map and identify mutations for two distinct inherited disorders that both affect a single breed, the Cavalier King Charles Spaniel. We investigated episodic falling (EF), a paroxysmal exertion-induced dyskinesia, alongside the phenotypically distinct condition congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID), commonly known as dry eye curly coat syndrome. EF is characterised by episodes of exercise-induced muscular hypertonicity and abnormal posturing, usually occurring after exercise or periods of excitement. CKCSID is a congenital disorder that manifests as a rough coat present at birth, with keratoconjunctivitis sicca apparent on eyelid opening at 10–14 days, followed by hyperkeratinisation of footpads and distortion of nails that develops over the next few months. We undertook a GWAS with 31 EF cases, 23 CKCSID cases, and a common set of 38 controls and identified statistically associated signals for EF and CKCSID on chromosome 7 (Praw 1.9×10−14; Pgenome=1.0×10−5) and chromosome 13 (Praw 1.2×10−17; Pgenome=1.0×10−5), respectively. We resequenced both the EF and CKCSID disease-associated regions in just five dogs and identified a 15,724 bp deletion spanning three exons of BCAN associated with EF and a single base-pair exonic deletion in FAM83H associated with CKCSID. Neither BCAN or FAM83H have been associated with equivalent disease phenotypes in any other species, thus demonstrating the ability to use the domestic dog to study the genetic basis of more than one disease simultaneously in a single breed and to identify multiple novel candidate genes in parallel."
Congenital keratoconjunctivitis sicca and ichthyosiform dermatosis in Cavalier King Charles spaniel dogs – part II: candidate gene study. Claudia Hartley, Keith C. Barnett, Louise Pettitt, Oliver P. Forman, Sarah Blott, Cathryn S. Mellersh. Vet.Ophth. Feb 2012. Quote: "Purpose: To identify causative mutation(s) for congenital keratoconjunctivitis sicca and ichthyosiform dermatosis (CKCSID) in Cavalier King Charles spaniel (CKCS) dogs using a candidate gene approach. Methods: DNA samples from 21 cases/parents were collected. Canine candidate genes (CCGs) for similar inherited human diseases were chosen. Twenty-eight candidate genes were identified by searching the Pubmed OMIM database (http://www.ncbi.nlm.nih.gov/omim). Canine orthologues of human candidate genes were identified using the Ensembl orthologue prediction facility (http://www.ensembl.org/index.html). Two microsatellites flanking each candidate gene were selected, and primers to amplify each microsatellite were designed using the Whitehead Institute primer design website (http://frodo.wi.mit.edu/primer3/). The microsatellites associated with all 28 CCGs were genotyped on a panel of 21 DNA samples from CKCS dogs (13 affected and eight carriers). Genotyping data was analyzed to identify markers homozygous in affected dogs and heterozygous in carriers (homozygosity mapping). Results: None of the microsatellites associated with 25 of the CCGs displayed an association with CKCSID in the 21 DNA samples tested. Three CCGs associated microsatellites were monomorphic across all samples tested. Conclusions: Twenty-five CCGs were excluded as cause of CKCSID. Three CCGs could not be excluded from involvement in the inheritance of CKCSID."
