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Background A 7‐month‐old female spayed English Springer Spaniel (ESS) was evaluated for spontaneous hemoperitoneum. Hyperfibrinolysis was identified on thromboelastography. Hypothesis/Objectives To identify a genetic mutation causing congenital hyperfibrinolysis in the proband and evaluate the prevalence of the mutation in the ESS breed. Animals Client‐owned ESS with hemorrhage and a non‐affected littermate. Samples of DNA from 3 ESS, 1 Welsh Springer Spaniel (WSS) with unexplained hemorrhage, and 199 ESS with no history of hemorrhage. Methods Whole genome sequencing (WGS) of the proband with variant filtering against an in‐house WGS database of 671 presumably unaffected dogs identified a deleterious variant of SERPINE1 unique to the proband, which encodes for plasminogen activator inhibitor 1 (PAI‐1). SERPINE1 was genotyped in the remaining animal population by Sanger sequencing or a Taqman assay. Liquid chromatography tandem mass spectrometry (LC–MS/MS) was performed on platelet pellets from the proband, a littermate, and three unrelated healthy ESS. Results Whole genome sequencing of the proband identified a unique homozygous insertion at chr6:8640592 in exon 1 of SERPINE1, which is predicted to cause a premature stop codon. The unaffected littermate was heterozygous for the mutation. Two unrelated ESS and 1 WSS with post‐operative hemorrhage were homozygous for the mutation. Absence of PAI‐1 in the proband's platelets was documented using LC–MS/MS. Conclusions and Clinical Importance This novel mutation in SERPINE1 is associated with the absence of the PAI‐1 protein in platelets and might cause hemorrhage because of hyperfibrinolysis in ESS and related breeds.

A 3‐year‐old spayed female English Springer Spaniel was presented twice 4 months apart for investigation of hematuria and pollakiuria without urinary tract infection. Both ultrasound examinations identified a stable craniodorsal bladder wall thickening. The first cystoscopic biopsy samples indicated lymphoplasmacytic cystitis and the second polypoid cystitis. The dog was represented 8 months later for recurrent clinical signs despite medical management. Although the ultrasound examination showed stable disease, repeat cystoscopic biopsy identified transitional cell carcinoma (TCC), confirmed on tissue removed by partial cystectomy. No BRAF mutation was ever detected in urine or tissue samples. To our knowledge, this case represents the first report of presumptive malignant transformation of polypoid cystitis into an apical TCC in a dog. Dogs with polypoid cystitis should be followed closely and surgical management considered if rapid resolution is not achieved with medical management.

Background Two Labrador retriever littermates were identified based on incidentally noted marked microcytosis and inappropriate metarubricytosis. Muscle atrophy was noted and associated with distinctive pathological findings in biopsy samples from 1 dog studied. The disorder represents a rare clinical entity of suspected congenital dyserythropoiesis and polymyopathy. Clinicopathologic changes were similar to a previously reported syndrome of congenital dyserythropoiesis, congenital polymyopathy, and cardiac disease in 3 related English Springer Spaniel (ESS) dogs, but the dogs reported here did not have apparent cardiac disease. Interventions Bone marrow aspiration, electromyography, muscle biopsies, and an echocardiogram were performed on dog 1. Results supported dyserythropoiesis and congenital polymyopathy similar to reports in ESS dogs, but did not identify obvious cardiac disease. Conclusion The clinicopathologic changes of dyserythropoiesis and polymyopathy provide an easily recognizable phenotype for what appears to be a low morbidity syndrome. Early recognition may decrease unnecessary testing or euthanasia.

Background Paramyotonia congenita and Brody disease are well‐described conditions in humans, characterized by exercise‐induced myotonic‐like muscle stiffness. A syndrome similar to Brody disease has been reported in cattle. Reports of a similar syndrome in dogs are scarce. Objectives To define and describe the clinical, diagnostic, and genetic features and disease course of paradoxical pseudomyotonia in Spaniel dogs. Animals Seven client‐owned dogs (4 English Springer Spaniels and 3 English Cocker Spaniels) with clinically confirmed episodes of exercise‐induced generalized myotonic‐like muscle stiffness. Methods Sequential case study. Results All dogs were <24 months of age at onset. The episodes of myotonic‐like generalized muscle stiffness always occurred with exercise, and spontaneously resolved with rest in <45 seconds in all but 1 dog. Extreme outside temperatures seemed to considerably worsen episode frequency and severity in most dogs. Complete blood count, serum biochemistry including electrolytes, urinalysis, brain magnetic resonance imaging, cerebrospinal fluid analysis, electromyography, motor nerve conduction velocity, ECG, and echocardiography were unremarkable. Muscle biopsy samples showed moderate but nonspecific muscle atrophy. The episodes seemed to remain stable or decrease in severity and frequency in 6/7 dogs, and often could be decreased or prevented by avoiding the episode triggers. The underlying genetic cause is not identified yet, because no disease‐causing variants could be found in the coding sequence or splice sites of the 2 major candidate genes, SCN4A and ATP2A1. Conclusions and Clinical Importance Paradoxical pseudomyotonia is a disease affecting Spaniels. It is of variable severity but benign in most cases.

Canine idiopathic epilepsy is a common neurological disease affecting both purebred and crossbred dogs. Various breed-specific cohort, epidemiological and genetic studies have been conducted to date, which all improved our knowledge and general understanding of canine idiopathic epilepsy, and in particular our knowledge of those breeds studied. However, these studies also frequently revealed differences between the investigated breeds with respect to clinical features, inheritance and prevalence rates. Awareness and observation of breed-specific differences is important for successful management of the dog with epilepsy in everyday clinical practice and furthermore may promote canine epilepsy research. The following manuscript reviews the evidence available for breeds which have been identified as being predisposed to idiopathic epilepsy with a proven or suspected genetic background, and highlights different breed specific clinical features (e.g. age at onset, sex, seizure type), treatment response, prevalence rates and proposed inheritance reported in the literature. In addition, certain breed-specific diseases that may act as potential differentials for idiopathic epilepsy are highlighted.

In this report, we describe a novel genetic basis for congenital dyserythropoietic anemia and polymyopathy in Labrador Retriever littermates characterized by incidental detection of marked microcytosis, inappropriate metarubricytosis, pelvic limb weakness and muscle atrophy. A similar syndrome has been described in English Springer Spaniel littermates with an early onset of anemia, megaesophagus, generalized muscle atrophy and cardiomyopathy. Muscle histopathology in both breeds showed distinctive pathological changes consistent with congenital polymyopathy. Using whole genome sequencing and mapping to the CanFam4 (Canis lupus familiaris reference assembly 4), a nonsense variant in the EHBP1L1 gene was identified in a homozygous form in the Labrador Retriever littermates. The mutation produces a premature stop codon that deletes approximately 90% of the protein. This variant was not present in the English Springer Spaniels. Currently, EHPB1L1 is described as critical to actin cytoskeletal organization and apical-directed transport in polarized epithelial cells, and through connections with Rab8 and a BIN1-dynamin complex generates membrane vesicles in the endocytic recycling compartment. Furthermore, EHBP1L1 knockout mice die early and develop severe anemia. The connection of EHBP1L1 to BIN1 and DMN2 functions is particularly interesting due to BIN1 and DMN2 mutations being causative in forms of centronuclear myopathy. This report, along with an independent study conducted by another group, are the first reports of an association of EHBP1L1 mutations with congenital dyserythropoietic anemia and polymyopathy.

Hereditary myopathies are well documented in dogs, whereas hereditary dyserythropoietic anemias are rarely seen. The aim of this study was to further characterize the clinical and clinicopathological features of and to identify the causative genetic variant for a dyserythropoietic anemia and myopathy syndrome (DAMS) in English springer spaniel dogs (ESSPs). Twenty-six ESSPs, including five dogs with DAMS and two puppies that died perinatally, were studied. Progressive weakness, muscle atrophy—particularly of the temporal and pelvic muscles—trismus, dysphagia, and regurgitation due to megaesophagus were observed at all ages. Affected dogs had a non-regenerative, microcytic hypochromic anemia with metarubricytosis, target cells, and acanthocytes. Marked erythroid hyperplasia and dyserythropoiesis with non-orderly maturation of erythrocytes and inappropriate microcytic metarubricytosis were present. Muscle biopsies showed centralized nuclei, central pallor, lipocyte infiltrates, and fibrosis, which was consistent with centronuclear myopathy. The genome sequencing of two affected dogs was compared to 782 genomes of different canine breeds. A homozygous frameshift single-base deletion in EHBP1L1 was identified; this gene was not previously associated with DAMS. Pedigree analysis confirmed that the affected ESSPs were related. Variant genotyping showed appropriate complete segregation in the family, which was consistent with an autosomal recessive mode of inheritance. This study expands the known genotype–phenotype correlation of EHBP1L1 and the list of potential causative genes in dyserythropoietic anemias and myopathies in humans. EHBP1L1 deficiency was previously reported as perinatally lethal in humans and knockout mice. Our findings enable the genetic testing of ESSP dogs for early diagnosis and disease prevention through targeted breeding strategies.

Background A 5‐year‐old, healthy English Springer Spaniel died suddenly 4 months after delivering a litter of 7 puppies. Within 4 months of the dam's death, 3 offspring also died suddenly. Hypothesis Abnormal cardiac repolarization, caused by an inherited long QT syndrome, is thought to be responsible for arrhythmias leading to sudden death in this family. Animals Four remaining dogs from the affected litter and 11 related dogs. Methods Physical examination and resting ECG were done on the littermates and 9 related dogs. Additional tests on some or all littermates included echocardiogram with Doppler, Holter monitoring, and routine serum biochemistry. Blood for DNA sequencing was obtained from all 15 dogs. Results Three of 4 littermates examined, but no other dogs, had prolonged QT intervals with unique T‐wave morphology. DNA sequencing of the KCNQ1 gene identified a heterozygous single base pair mutation, unique to these 3 dogs, which changes a conserved amino acid from threonine to lysine and is predicted to change protein structure. Conclusions and Clinical Importance This family represents the first documentation in dogs of spontaneous familial QT prolongation, which was associated with a KCNQ1 gene mutation and sudden death. Although the final rhythm could not be documented in these dogs, their phenotypic manifestations of QT interval prolongation and abnormal ECG restitution suggested increased risk for sudden arrhythmic death. The KCNQ1 gene mutation identified is speculated to impair the cardiac repolarizing current IKs, similar to KCNQ1 mutations causing long QT syndrome 1 in humans.

This report describes a 10-month-old female, English springer spaniel that was referred to the surgical department for investigation of progressive exercise intolerance and stridor. After performing a complete blood test, thorough examination of the airway under a light plane of anaesthesia and CT of the head and thorax under general anaesthesia, bilateral laryngeal paralysis was diagnosed. Due to the dog’s age and the absence of other aetiologies and neurological abnormalities, a diagnosis of congenital laryngeal paralysis was reached.Unilateral arytenoid lateralisation was performed with cricoarytenoid and thyroarytenoid sutures. The dog had an uneventful recovery and was successfully discharged the day following surgery with no recurrent respiratory signs for six months postoperatively (at the time this case report was written). This is the first case report that describes congenital bilateral laryngeal paralysis in an English springer spaniel.

Medical records and liver histology of 68 English springer spaniels (ESS) with a histological diagnosis of CH were reviewed retrospectively. PCR was performed on liver tissue for canine adenovirus-1 (CAV-1), canine parvovirus, canine herpesvirus and pathogenic Leptospira species. Follow-up information was obtained to calculate survival times. Median age at presentation was three years seven months (range, seven months to eight years five months) and there were 48 female and 20 male dogs. Clinical signs were non-specific and five dogs were asymptomatic. All dogs had an increase in serum activity of one or more hepatobiliary enzymes. Histopathology demonstrated hepatocyte necrosis and apoptosis with varying amounts of fibrosis. A predominantly lymphoplasmacytic infiltrate throughout the hepatic parenchyma was found in all 68 dogs, but 45 of these dogs also had a neutrophilic component to the inflammatory infiltrate. There was no significant copper accumulation and no aetiological agent was identified by PCR. The median survival time was 189 days (range, 1 to 1211 days), 38 dogs died within three months and 12 dogs survived more than a year following diagnosis.