Cavalier King Charles Spaniel Dogs Research Articles

A Novel CARMIL2 Immunodeficiency Identified in a Subset of Cavalier King Charles Spaniels with Pneumocystis and Bordetella Pneumonia.

Pet dogs are a valuable natural animal model for studying relationships between primary immunodeficiencies and susceptibility to Pneumocystis and other opportunistic respiratory pathogens. Certain breeds, such as the Cavalier King Charles Spaniel, are over-represented for Pneumocystis pneumonia (PCP), suggesting the presence of a primary immunodeficiency in the breed. Here, we report the discovery of a CARMIL2 nonsense variant in three Cavalier King Charles Spaniel dogs with either PCP (n = 2) or refractory Bordetella pneumonia (n = 1). CARMIL2 encodes a protein that plays critical roles in T-cell activation and other aspects of immune function. Deleterious CARMIL2 variants have recently been reported in human patients with PCP and other recurrent pneumonias. In addition to opportunistic respiratory infection, the affected dogs also exhibited other clinical manifestations of CARMIL2 deficiencies that have been reported in humans, including early-onset gastrointestinal disease, allergic skin disease, mucocutaneous lesions, abscesses, autoimmune disorders, and gastrointestinal parasitism. This discovery highlights the potential utility of a natural canine model in identifying and studying primary immunodeficiencies in patients affected by PCP.

CASE REPORT: INHERITED MACROTHROMBOCYTOPENIA IN A CAVALIER KING CHARLES SPANIEL

A 11-month-old intact male Cavalier King Charles Spaniel (CKCS) dog was presented at the Teaching Hospital of National Chung Hsin University (NCHU-VMTH) due to thrombocytopenia without relevant clinical signs and no significant improvement after medication treatment. As per the complete blood profile, there was significant thrombocytopenia (platelet count 1–[Formula: see text] L) with mean platelet volume (MPV) ranging from 20.3 to 25.7[Formula: see text]fl. Tests for Babesia canis, B. gibsoni, Ehrlichia canis and Anaplasma phagocytophilum yielded negative results. Despite treatment with antibiotics and immunosuppressive drugs, the dog’s condition did not improve. The dog’s platelet morphology and absence of symptoms raised the suspicion of inherited macrothrombocytopenia. Genomic DNA sequencing analysis of the [Formula: see text]1-tubulin gene revealed a single-point mutation, specifically c.745[Formula: see text]G>A. This genetic analysis confirmed the presence of a [Formula: see text]1-tubulin mutation, marking the first reported case of such a mutation in a CKCS in Taiwan. Despite the diagnosis of this condition, both partial thromboplastin time (PTT) and active partial thromboplastin time (aPTT) were within normal ranges before neutering. When diagnosing the causes of thrombocytopenia in young patients, especially when there are no related clinical signs, it is crucial to consider prioritizing inherited macrothrombocytopenia, then thrombocytopenia secondary to parasite infection, or immune-mediated thrombocytopenia (IMT) to minimize unnecessary medication.

Diagnosis and surgical management of a type IVb dermoid sinus in a Cavalier King Charles Spaniel

AbstractA 6‐year‐old, male, neutered Cavalier King Charles Spaniel dog was referred with a 4‐year history of an intermittently draining fistula on the midline of the frontal bones of the skull. Magnetic resonance imaging and computed tomography scan of the head demonstrated an extra‐axial mass in the midline between the frontal lobes, contacting the meninges and extending rostrally through a defect in the frontal bones. The mass was surgically excised via a frontal craniotomy. Histopathology of the mass demonstrated stratified squamous and keratinising epithelium with adnexal structures, consistent with the diagnosis of a dermoid sinus. Previous reports have documented dermoid sinuses in the nasal region in dogs and cats with intracranial extension. This case report documents a dermoid sinus in the frontal region with intracranial extension in a dog, confirmed by advanced diagnostic imaging, histopathology, and successfully treated surgically.

Radiographic Evaluation of Left Atrial Size in Cavalier King Charles Spaniel Dogs with Mitral Valve Disease

Abstract Myxomatous mitral valve disease (MMVD) is one of the most common heart diseases in Cavalier King Charles spaniel (CKCS) dogs. The American College of Veterinary Internal Medicine (ACVIM) uses clinical, echocardiographic, and radiographic criteria to diagnose the disease, but measurement of vertebral left atrial size (VLAS) provides a simpler assessment. The aim of this study was to determine VLAS values in MMVD cases of CKCS and to investigate their clinical significance at different MMVD stages. Eighteen CKCS dogs of both sexes, different ages and weights, and different MMVD stages (6 at B1 stage, 6 at B2 stage, and 6 at C stage) were included in the study, as well as 6 healthy CKCS as control group A. We performed clinical, radiological, and echocardiographic examinations. VHS and VLAS values were significantly higher in the MMVD group than in the control group (p<0.001). VLAS showed high diagnostic accuracy in the detection of LA enlargement (area under the curve [AUC]: 0.98, cutoff ≥ 2.25, sensitivity: 88%, specificity: 100%, p<0.001). We also found high positive correlations between the VLAS and other values (LA /Ao, LVIDDn, and VHS) (r=0.88, r=0.88, and r=0.86, respectively) (p<0.001). It has been concluded that a VLAS value ≥2.25 can provide a meaningful diagnosis of left atrial enlargement in dogs with MMVD CKCS.

Evaluation of the Corrected QT Interval with Bazett’s Method in Cavalier King Charles Spaniel Dogs with Myxomatous Mitral Valve Disease

Abstract Myxomatous mitral valve disease (MMVD) is one of the most common heart diseases in dogs. The disease progresses faster in Cavalier King Charles Spaniel (CKCS) dogs and occurs at an earlier age. QT interval length reflects abnormalities in ventricular repolarization which may predispose to the formation of fatal arrhythmias such as torsades de pointes. A fast and accurate assessment is therefore essential. The study aimed to examine the changes in QT duration in MMVD cases of CKCS and to calculate the corrected QT durations with Bazett’s formula in various stages of the disease. The study included 20 CKCS dogs of both genders, various ages and weights, and different stages of MMVD (n=6 in B1 stage, n=6 in B2 stage, and n=8 in C stage), and 5 healthy CKCS which were included in the control group. Clinical, radiological, hematological, biochemical, echocardiographic, and electrocardiographic examinations were performed. The corrected QT interval duration in the MMVD group was longer than the control (p<0.05). However, there was no significant difference between B1, B2, and C. It was concluded that the corrected QT interval can give a significant distinction between healthy and MMVD CKCS dogs.

Diffusion Tensor Imaging in Syringomyelia Secondary to Chiari Malformation in Cavalier King Charles Spaniel—A Preliminary Study

Syringomyelia secondary to Chiari-like malformation (so-called CM-SM syndrome) is a common disorder in Cavalier King Charles Spaniels (CKCS) that is diagnosed using standard structural MRI, though imaging findings often do not correlate with the severity of clinical symptoms. Diffusion tensor imaging (DTI) is a technique that defines subtle microstructural changes in the course of many brain and spinal cord diseases, that are not visible on standard MRI. The aim of the study was to identify the correlation between the presence of clinical symptoms and DTI parameters, such as apparent diffusion coefficient (ADC) and fractional anisotropy (FA) within the spinal cord in the course of CM-SM. Study subjects included 18 dogs, CKCS with MRI-confirmed SM (SM group), and 12 CKCS dogs without SM (non-SM group). The SM group was divided into SM-symptomatic group (n = 8) and SM-asymptomatic group, n = 10). All dogs underwent same clinical and neurological assessment followed by MRI examination. All MRI studies were performed on a 1.5T MRI scanner. The MRI spine protocol included: transverse and sagittal T2-weighted images followed by DTI performed in the sagittal plane. The measurements of FA and ADC values were performed manually using the region of interest (ROI) method at the level of three intervertebral discs between C1 and C4. Notable differences in age and body weight were found. No significant differences in FA and ADC values between the SM and non-SM groups were found, but between non-SM, SM-asymptomatic and SM-symptomatic groups significant differences were found in ADC values in all three ROIs and in FA values in ROI-1 and ROI-3. SM-symptomatic dogs compared to non-SM, showed decreased FA value in ROI-1 and ROI-3 also increased ADC value in ROI-1, ROI-2 and ROI-3. SM-symptomatic dogs compared to SM-asymptomatic showed also decreased FA value in ROI-1 and ROI-3, and also increased ADC value in ROI-1, ROI-2 and ROI-3. The results suggest that the values of DTI parameters correlate with the severity of clinical symptoms in the course of CM-SM in animals. The use of DTI evaluation of CM-SM patients carries a potential value as a clinically relevant protocol for an objective assessment of the spinal cord.

ETIOPATHOGENETIC MECHANISM IN DOG SYRINGOMYELIA

Syringomyelia (MS) is a condition characterized by the development of cavities in the parenchyma of the spinal cord (sirinx). Cavalier King Charles Spaniel (CKCS) dogs have a high incidence of Chiari malformation. The breed was born in 1928, from dogs of the King Charles Spaniel breed, a favorite dog of royal and noble families, with the aim of recreating a dog similar to the one present in the portraits of King Charles II, during the restoration period. The CKCS breed is native to the United Kingdom, being composed of small brachycephalic specimens - toy, a distinctive feature of the breed being the flattened and miniaturized appearance of the head (Rusbridge & Knowler, 2003).
 Syringomyelia is a topical and real interest topic in canine neuropathology, representing the topic of numerous researches, both due to the many unknowns of the evolution of the diseases, and the fact that at present there is no effective treatment.

Dorsal horn volume loss and pain pathway changes in Cavalier King Charles Spaniels with syringomyelia, signs of pain, and phantom scratching.

Central neuropathic pain is a core clinical sign of syringomyelia in humans and Cavalier King Charles Spaniel (CKCS) dogs. This histopathological study used spinal cords from CKCS dogs with syringomyelia to investigate the following conditions: (1) whether specific structural cervical spinal cord entities involved in nociception were affected by loss of neuroparenchyma or other pathological changes in CKCS dogs with pain-related behaviour and phantom scratching, (2) whether pain-related behaviour or phantom scratching correlated with loss of a specific anatomical entity or upregulation of glia cells, and (3) whether syringomyelia-related lesions affected specific functional spinal cord units of nociception. Spinal cord segments C1-C8 from CKCS dogs with magnetic resonance imaging-confirmed syringomyelia and clinical signs of pain and phantom scratching (n = 8) were compared with those from CKCS dogs without syringomyelia (n = 4). Dogs with unilateral scratching (n = 7) had a volume loss ( P = 0.043) of the dorsal horn laminae I-III in the ipsilateral side compared with the contralateral dorsal horn. A clear pattern of ipsilateral changes in the dorsal root entry zone characterised by deafferentation and reorganization of first-order axons into deeper laminae was found in cases with lateralised scratching. Significant changes in cell number density were not found for astrocytes or microglia, suggesting that the dogs represented cases of end-stage syringomyelia and thus could not reveal astrogliosis and microgliosis, which may be involved in the early phases of syrinx development and phantom scratching. The present relationship between clinical findings and dorsal horn and pain pathway pathology in CKCS dogs suggests that these dogs may be of interest as a supplement to experimental model pain research.

Ventriculomegaly in Cavalier King Charles Spaniels with Chiari-like malformation: relationship with clinical and imaging findings.

The objective of this study was to calculate lateral ventricles dimension in Cavalier King Charles Spaniel dogs with Chiari-like malformation and investigate the association between ventriculomegaly and signalment, clinical signs, ventricular asymmetry, grade of Chiari-like malformation, syringomyelia and index of medullary kinking. Retrospectively, 43 client-owned Cavalier King Charles Spaniels, older than 1 year of age, with magnetic resonance imaging diagnosis of Chiari-like malformation were enrolled. Initial and follow-up (up to 36 months) clinical status was graded. Images were reviewed to quantify the enlargement of lateral ventricles, evaluate ventricular symmetry, grade of Chiari-like malformation, grade of syringomyelia and medullary kinking index. Cases presenting epileptic seizures during the evaluation period were also recorded. The most common initial clinical signs were scratching and neck pain. Ventriculomegaly was identified in 70% of dogs, Chiari-like malformation grade 2 was observed in 77% of cases, ventricular asymmetry and syringomyelia were identified in 54% and 80% of dogs, respectively; the median medullary kinking index was 37.77%. Moreover, 28% of dogs presented epileptic seizures. No significant association was identified between dimension of lateral ventricles and signalment, clinical signs, and imaging findings; no significant association was identified between ventriculomegaly and epilepsy (P≥0.05). In conclusion, the prevalence of ventriculomegaly in Cavalier King Charles Spaniels is high but this finding does not seem related to the severity of clinical signs, presence of Chiari-like malformation, syringomyelia and craniocervical junction abnormalities such as medullary kinking.

Comparative transcriptomic profiling of myxomatous mitral valve disease in the cavalier King Charles spaniel

BackgroundAlmost all elderly dogs develop myxomatous mitral valve disease by the end of their life, but the cavalier King Charles spaniel (CKCS) has a heightened susceptibility, frequently resulting in death at a young age and suggesting that there is a genetic component to the condition in this breed. Transcriptional profiling can reveal the impact of genetic variation through differences in gene expression levels. The aim of this study was to determine whether expression patterns were different in mitral valves showing myxomatous degeneration from CKCS dogs compared to valves from non-CKCS dogs.ResultsGene expression patterns in three groups of canine valves resulted in distinct separation of normal valves, diseased valves from CKCS and diseased valves from other breeds; the latter were more similar to the normal valves than were the valves from CKCS. Gene expression patterns in diseased valves from CKCS dogs were quite different from those in the valves from other dogs, both affected and normal. Patterns in all diseased valves (from CKCS and other breeds) were also somewhat different from normal non-diseased samples. Analysis of differentially expressed genes showed enrichment in GO terms relating to cardiac development and function and to calcium signalling canonical pathway in the genes down-regulated in the diseased valves from CKCS, compared to normal valves and to diseased valves from other breeds. F2 (prothrombin) (CKCS diseased valves compared to normal) and MEF2C pathway activation (CKCS diseased valves compared to non-CKCS diseased valves) had the strongest association with the gene changes. A large number of genes that were differentially expressed in the CKCS diseased valves compared with normal valves and diseased valves from other breeds were associated with cardiomyocytes including CASQ2, TNNI3 and RYR2.ConclusionTranscriptomic profiling identified gene expression changes in CKCS diseased valves that were not present in age and disease severity-matched non-CKCS valves. These genes are associated with cardiomyocytes, coagulation and extra-cellular matrix remodelling. Identification of genes that vary in the CKCS will allow exploration of genetic variation to understand the aetiology of the disease in this breed, and ultimately development of breeding strategies to eliminate this disease from the breed.

Pregabalin alleviates clinical signs of syringomyelia-related central neuropathic pain in Cavalier King Charles Spaniel dogs: a randomized controlled trial

ObjectiveWe aimed to assess the efficacy and benefit-risk profile of pregabalin (PGN) to reduce the clinical signs of central neuropathic pain (CNeP) as reflected by scratching episodes in dogs with symptomatic syringomyelia (SM). Study designRandomized, double-blind, placebo-controlled crossover study. AnimalsA total of 12 client-owned Cavalier King Charles Spaniels (age, 1.1–7.4 years, bodyweight, 8.2–10.8 kg) with magnetic resonance imaging-confirmed SM and clinical signs of CNeP. MethodsDogs were randomized to either PGN 150 mg or placebo for 25 days, followed by 48 hour washout period before crossover to the alternate phase of 25 days. The primary outcome was defined as number of scratching events during 10 minutes of video-recorded physical activity. Treatment effect was estimated using a generalized estimation equation model. Benefit-risk and quality of life assessments were obtained through owner interviews focusing on potential adverse events. ResultsThe treatment effect estimate was an 84% (95% confidence interval = 75–89%) reduction in mean number of scratching events relative to baseline compared with placebo (p < 0.0001). Owner-assessed satisfactory quality of life was status quo and rated as ‘good’ or ‘could not be better’ in six/11 dogs and improved in four/11 dogs. The most prevalent adverse events were increased appetite in nine/12 dogs and transient ataxia in nine/12 dogs. There was one dog withdrawn by the owner 7 days after crossover to PGN owing to persistent ataxia. No dogs needed rescue analgesia during the trial. Conclusions and clinical relevancePGN is superior to placebo in the reduction of clinical signs of SM-related CNeP in dogs. At a dose range of 13–19 mg kg–1 orally twice daily, the encountered adverse events were acceptable to all but one owner.

Clinical and diagnostic imaging features of Chiari-like malformation and Syringomyelia in Cavalier King Charles Spaniel dogs – retrospective study

Clinical and diagnostic imaging features of Chiari-like malformation and Syringomyelia in Cavalier King Charles Spaniel dogs – retrospective study

Retrospective study of 37 Cavalier King Charles Spaniel dogs diagnosed with Chiari-like malformation and Syringomyelia

Abstract Chiari-like malformation represents a congenital anomaly that affects the bony cranial base and the hindbrain, leading to fluid filled cavities formation in the spinal cord, condition named Syringomyelia. This paper aims to assess the variety of the clinical signs and to evaluate the magnetic resonance imaging findings in thirty- seven Cavalier King Charles Spaniel dogs. The study was performed over a four-year period, from 2013 to 2017, all cases underwent neurological examination, full diagnostic work-up, including magnetic resonance imaging scans of the brain, cervical and upper thoracic spinal cord. Thirty-seven dogs were included in this study, 23 females and 14 males, with a mean age of 3.6±2.1years. The commonest clinical findings encountered were neuropathic pain and vocalization, seen in all 37 cases, followed by scratching, facial rubbing, paw licking, air licking, tail chasing, seizures and unilateral facial paralysis. Different grades of cerebellar herniation and cervical syrinxes were noted in all cases, other magnetic resonance imaging findings encountered were medullary kinking, presyrinx and ventriculomegaly. In establishing the diagnosis of the Chiari-like malformation and Syringomyelia, the breed, clinical history and the symptomatology are very important, but only magnetic resonance imaging technique can provide quantitative assessment of the nervous system lesions.

Retrospective study of 16 Cavalier King Charles Spaniel dogs diagnosed with Chiari-Like Malformation and Syringomyelia. Magnetic Resonance Imaging and Surgical Management

Chiari-like malformation (CM) and Syringomyelia (SM) are complex neurological disorders, that affects the brain and respectively the spinal cord. These conditions affect certain toy breed dogs, among which the Cavalier King Charles Spaniel breed is overrepresented, causing numerous clinical signs, of which the neurological pain is commonly observed.The purpose of this research was to describe the CM/SM magnetic resonance images, to discuss the medical management and to track the outcome of the patients. All of the 16 Cavalier King Charles Spaniel dogs underwent surgical treatment, consisting of cranio-cervical decompression, combined with drug therapy.Thirteen of the 16 cases presented good results with clinical improvement of the symptomatology, escpecially decreasing the neuropathic pain, and increasing the quality of life. The other 3 cases presented no improvement of the symptomatology.

Congenital pleuroperitoneal hernia presenting as gastrothorax in five cavalier King Charles spaniel dogs

Five cavalier King Charles spaniels were examined for acute onset of respiratory distress. Thoracic radiographs demonstrated diaphragmatic hernia and tension gastrothorax, visible as a distended stomach occupying the left caudal thoracic cavity. Exploratory midline coeliotomy confirmed congenital pleuroperitoneal diaphragmatic hernia with herniation and dilatation of the stomach. The hernia configuration was consistent in all cases, with a defect affecting the left diaphragmatic crus. Congenital pleuroperitoneal diaphragmatic hernia is a rare condition caused by a defect in the dorsolateral diaphragm. Defects of the left crus of the diaphragm could result in the herniation of the stomach into the thoracic cavity with possible subsequent tension gastrothorax. Cavalier King Charles spaniels may have a predisposition to this condition. Tension gastrothorax is an acute life-threatening consequence of gastric herniation through a diaphragmatic defect that must be promptly recognised and surgically treated.

A genome-wide association study identifies candidate loci associated to syringomyelia secondary to Chiari-like malformation in Cavalier King Charles Spaniels

BackgroundSyringomyelia (SM) is a common condition affecting brachycephalic toy breed dogs and is characterized by the development of fluid-filled cavities within the spinal cord. It is often concurrent with a complex developmental malformation of the skull and craniocervical vertebrae called Chiari-like malformation (CM) characterized by a conformational change and overcrowding of the brain and cervical spinal cord particularly at the craniocervical junction. CM and SM have a polygenic mode of inheritance with variable penetrance.ResultsWe identified six cranial T1-weighted sagittal MRI measurements that were associated to maximum transverse diameter of the syrinx cavity. Increased syrinx transverse diameter has been correlated previously with increased likelihood of behavioral signs of pain. We next conducted a whole genome association study of these traits in 65 Cavalier King Charles Spaniel (CKCS) dogs (33 controls, 32 with extreme phenotypes). Two loci on CFA22 and CFA26 were found to be significantly associated to two traits associated with a reduced volume and altered orientation of the caudal cranial fossa. Their reconstructed haplotypes defined two associated regions that harbor only two genes: PCDH17 on CFA22 and ZWINT on CFA26. PCDH17 codes for a cell adhesion molecule expressed specifically in the brain and spinal cord. ZWINT plays a role in chromosome segregation and its expression is increased with the onset of neuropathic pain. Targeted genomic sequencing of these regions identified respectively 37 and 339 SNPs with significantly associated P values. Genotyping of tagSNPs selected from these 2 candidate loci in an extended cohort of 461 CKCS (187 unaffected, 274 SM affected) identified 2 SNPs on CFA22 that were significantly associated to SM strengthening the candidacy of this locus in SM development.ConclusionsWe identified 2 loci on CFA22 and CFA26 that contained only 2 genes, PCDH17 and ZWINT, significantly associated to two traits associated with syrinx transverse diameter. The locus on CFA22 was significantly associated to SM secondary to CM in the CKCS dog breed strengthening its candidacy for this disease. This study will provide an entry point for identification of the genetic factors predisposing to this condition and its underlying pathogenic mechanisms.

Angiostrongylus vasorum infection in dogs from a cardiopulmonary dirofilariosis endemic area of Northwestern Italy: a case study and a retrospective data analysis

BackgroundIn Italy, Angiostrongylus vasorum, an emergent parasite, is being diagnosed in dogs from areas considered free of infection so far. As clinical signs are multiple and common to other diseases, its diagnosis can be challenging. In particular, in areas where angiostrongylosis and dirofilariosis overlap, a misleading diagnosis of cardiopulmonary dirofilariosis might occur even on the basis of possible misleading outcomes from diagnostic kits.Case presentationTwo Cavalier King Charles spaniel dogs from an Italian breeding in the Northwest were referred to a private veterinary hospital with respiratory signs. A cardiopulmonary dirofilariosis was diagnosed and the dogs treated with ivermectin, but one of them died. At necropsy, pulmonary oedema, enlargement of tracheo-bronchial lymphnodes and of cardiac right side were detected. Within the right ventricle lumen, adults of A. vasorum were found. All dogs from the same kennel were subjected to faecal examination by FLOTAC and Baermann’s techniques to detect A. vasorum first stage larvae; blood analysis by Knott’s for Dirofilaria immitis microfilariae, and antigenic tests for both A. vasorum (Angio Detect™) and D.immitis (DiroCHEK® Heartworm, Witness®Dirofilaria). The surviving dog with respiratory signs resulted positive for A. vasorum both at serum antigens and larval detection. Its Witness® test was low positive similarly to other four dogs from the same kennel, but false positive results due to cross reactions with A. vasorum were also considered. No dogs were found infected by A. vasorum.Eventually, the investigation was deepened by browsing the pathological database of Veterinary Pathology Laboratories at Veterinary School of Milan University through 1998–2016, where 11 cases of angiostrongylosis were described. Two out of 11 dogs had a mixed infection with Crenosoma vulpis.ConclusionThe study demonstrates the need for accurate surveys to acquire proper epidemiological data on A. vasorum infection in Northwestern Italy and for appropriate diagnostic methods. Veterinary clinicians should be warned about the occurrence of this canine parasite and the connected risk of a misleading diagnosis, particularly in areas endemic for cardiopulmonary dirofilariosis.

Whole genome sequencing reveals a 7 base-pair deletion in DMD exon 42 in a dog with muscular dystrophy

Dystrophin is a key cytoskeletal protein coded by the Duchenne muscular dystrophy (DMD) gene located on the X-chromosome. Truncating mutations in the DMD gene cause loss of dystrophin and the classical DMD clinical syndrome. Spontaneous DMD gene mutations and associated phenotypes occur in several other species. The mdx mouse model and the golden retriever muscular dystrophy (GRMD) canine model have been used extensively to study DMD disease pathogenesis and show efficacy and side effects of putative treatments. Certain DMD gene mutations in high-risk, the so-called hot spot areas can be particularly helpful in modeling molecular therapies. Identification of specific mutations has been greatly enhanced by new genomic methods. Whole genome, next generation sequencing (WGS) has been recently used to define DMD patient mutations, but has not been used in dystrophic dogs. A dystrophin-deficient Cavalier King Charles Spaniel (CKCS) dog was evaluated at the functional, histopathological, biochemical, and molecular level. The affected dog’s phenotype was compared to the previously reported canine dystrophinopathies. WGS was then used to detect a 7 base pair deletion in DMD exon 42 (c.6051-6057delTCTCAAT mRNA), predicting a frameshift in gene transcription and truncation of dystrophin protein translation. The deletion was confirmed with conventional PCR and Sanger sequencing. This mutation is in a secondary DMD gene hotspot area distinct from the one identified earlier at the 5′ donor splice site of intron 50 in the CKCS breed.

Low-field MRI and multislice CT for the detection of cerebellar (foramen magnum) herniation in Cavalier King Charles Spaniels.

BackgroundCavalier King Charles Spaniels (CKCS) have a high prevalence of Chiari‐like malformation (CM). Herniation of the cerebellum into the foramen magnum is a key diagnostic feature for CM. Midsagittal MR images are the preferred technique for visualizing cerebellar herniation (CH).ObjectiveTo investigate whether CT can be used to diagnose CH.AnimalsFifteen client‐owned CKCS dogs referred for investigation of the brain and cranial cervical spine on MRI and CT.MethodsTwo reviewers retrospectively analyzed midsagittal T1WSE and T2WSE MR images and midsagittal pre‐ and postcontrast 2D multiplanar reformatted CT images from each dog for the presence of CH. And, if present, the length (mm, CHL) of the herniation was measured. The results were analyzed statistically.ResultsThere was no significant difference between the different observers and techniques for the detection of CH and measurement of CHL. Overall, the CHL was longer on the CT images.Conclusion and Clinical ImportanceBoth techniques are useful for detecting CH and measuring CHL. Because CHL does not have a known direct impact on the clinical presentation of CM, CT can be used as a diagnostic tool in a routine clinical practice for CM in CKCS when MRI is not available. We emphasize that MRI is the standard screening technique in CKCS for breeding purposes to detect the presence of CM and SM and, at the current time, CT cannot replace MRI.

Syringomyelia: determining risk and protective factors in the conformation of the Cavalier King Charles Spaniel dog.

BackgroundSyringomyelia (SM) is a painful neurological condition, prevalent in brachycephalic toy breeds including the Cavalier King Charles Spaniel (CKCS). In these breeds, SM is typically secondary to Chiari-like Malformation (CM). There has been much debate in the scientific and veterinary communities to what extent head shape is indicative of either pathology, especially as certain craniosynostosis syndromes in humans (highly associated with CM) have characteristic facial and cranial morphologies. Elucidating a risk morphology would allow for selection away from these traits and proffer further breeding guidelines for the condition.Dogs were measured in multiple countries by means of a standardised bony landmark measuring protocol and photo analysis by blinded, trained researchers.ResultsThe results found two significant risk factors in the conformation of the CKCS: extent of brachycephaly and distribution of cranium. The study identified a greater amount of cranium distributed caudally (relative to the amount distributed rostrally) to be significantly protective against syrinx development at the levels of three years of age, five years of age and when comparing a sample of SM clear individuals over the age of five to those affected younger than three years of age. A decreased cephalic index (decreasing brachycephaly) was significantly protective at the latter level. Cephalic index and caudal cranium distribution exhibited a negative, linear relationship. Cephalic index demonstrated a positive linear relationship with the amount of doming of the head.ConclusionsThis study proposes a risk phenotype of brachycephaly with resulting rostrocaudal doming that is more rostrally distributed and hence sloping caudally.The results of this study may allow for selection against risk aspects of conformation in the CKCS in combination with the British Veterinary Association/Kennel Club CM/SM scheme to enable reduction in CM/SM incidence. Further research comparing this external risk phenotype to the internal presentation upon MRI would determine how these features are indicative of syrinx development. Utilising breeds in which CM free individuals are more available may allow for validation of this risk phenotype for CM or determine alternatives.