Age-related thoracic radiographic changes in golden and labrador retriever muscular dystrophy

Golden retriever and Labrador retriever muscular dystrophy are inherited progressive degenerative myopathies that are used as models of Duchenne muscular dystrophy in man. Thoracic lesions were reported to be the most consistent radiographic finding in golden retriever dogs in a study where radiographs were performed at a single-time point. Muscular dystrophy worsens clinically over time and longitudinal studies in dogs are lacking. Thus our goal was to describe the thoracic abnormalities of golden retriever and Labrador retriever dogs, to determine the timing of first expression and their evolution with time. To this purpose, we retrospectively reviewed 390 monthly radiographic studies of 38 golden retrievers and six Labrador retrievers with muscular dystrophy. The same thoracic lesions were found in both golden and Labrador retrievers. They included, in decreasing frequency, flattened and/or scalloped diaphragmatic shape (43/44), pulmonary hyperinflation (34/44), hiatal hernia (34/44), cranial pectus excavatum (23/44), bronchopneumonia (22/44), and megaesophagus (14/44). The last three lesions were not reported in a previous radiographic study in golden retriever dogs. In all but two dogs the thoracic changes were detected between 4 and 10 months and were persistent or worsened over time. Clinically, muscular dystrophy should be included in the differential diagnosis of dogs with a combination of these thoracic radiographic findings.     

Radiographic,MRI, and CT findings in a young dog with Becker-like muscular dystrophy

An 8-month-old, male, crossbreed dog was presented for macroglossia, reduced mandibular extension, ptyalism, dysphagia, and regurgitation. Serum creatine kinase and aspartate aminotransferase activity were markedly increased. Thoracic radiographs showed an axial gastro-esophageal hiatal hernia, diaphragmatic thickening, and asymmetry. Magnetic resonance imaging of the head showed a severely enlarged tongue, symmetric increase in size of the geniohyoid and mylohyoid muscles, and diffuse masticatory hypomyotrophy. Whole-body CT ruled out other musculoskeletal abnormalities and further characterized the radiographic and MRI findings. Muscular histopathology was consistent with Becker muscular dystrophy.     

The electroretinographic phenotype of dogs with Golden Retriever muscular dystrophy

Objective To characterize the flash electroretinogram (ERG) in the Golden Retriever muscular dystrophy (GRMD) dog and to compare the results with those from a control group of Golden Retrievers. To investigate whether similar abnormalities of the ERG as those found in a majority of human patients with Duchenne muscular dystrophy (DMD) are also observed in the GRMD dog, the canine model for DMD. Animals Five GRMD dogs and five age‐matched clinically normal Golden Retrievers. Procedure An ophthalmic examination was carried out prior to performing electroretinography under general anesthesia. Rod, combined rod–cone and oscillatory potentials responses were recorded after dark adaptation. Responses to 30‐Hz‐flicker were recorded after light adaptation. The ERG responses of the GRMD dogs were compared with those of the control dogs by use of a Wilcoxon signed rank test. Results GRMD dogs had significantly reduced a and b‐wave amplitudes after dim white flash stimuli (rod response) and reduced a‐wave amplitude after bright white flash stimuli (rod–cone response). Conclusion and clinical relevance The ERG abnormalities observed in the GRMD dog suggest a dysfunction in the rod signaling pathway. These ERG alterations are different from those observed in human patients with DMD.     

RADIOGRAPHIC AND ULTRASONOGRAPHIC FEATURES OF HYPERTROPHIC FELINE MUSCULAR DYSTROPHY IN TWO CATS

Hypertrophic fellne musculer dystrophy has been reported as an X-linked inherited deficiency of a cytoskeletal myofiber protein called dystrophin. This report deserlbes the radiographic and ultrasonographic abnormalities of two male littermate domestic short-hair cats and reviews the previous reported findings assoclated with hypertrophic feline muscular dystrophy. The thoracic radiographic abnormalities included: progressive cardiomegaly, large convex, scalloped irregularities associated with the vetral aspect of the diaphragm, and variable degrees of esophageal dilation (megaesophagus) with associated cranioventral aspiration pneumonia. Echocardiographic features included: concentric left vetricular wall thickening, increased left ventricular and diastolic and systolic dimensions, and an increase in endocardial echogenicity. Abdominal radiographic abnormalities included: hepatosplenomegaly, peritoneal effusion, renomegaly, adrenal gland mineralization, and paralumbar and diaphragmatic musculature enlargement. Abdomlnal ultrasonographic abnormalities included: irregularly thickened muscular portion of the diaphragm; hypoechogenicity of the liver; peritoneal effusion; hepatosplenomegaly; renomegaly with hyperechoic cortex and medulla; and adrenal gland mineralization. The irregular scalloped appearance of the diaphragm (particularly along the ventral/sternal margin) was a consistenl radiographic abnormlity in the two cats with hypertrophic feline muscular dystrophy after the age of 7 months. This finding was confirmed by ultrasound as a thickened irregular, hyperechoic diaphragm. A diagnosis of hypertrophic feline muscular dystrophy should be strongly suspected if this abnormality is identified.     

Physical therapy assessment tools to evaluate disease progression and phenotype variability in Golden Retriever muscular dystrophy

Dogs suffering from Golden Retriever muscular dystrophy (GRMD) present symptoms that are similar to human patients with Duchenne muscular dystrophy (DMD). Phenotypic variability is common in both cases and correlates with disease progression and response to therapy. Physical therapy assessment tools were used to study disease progression and assess phenotypic variability in dogs with GRMD. At 5 (T0), 9 (T1), 13 (T2) and 17 (T3) months of age, the physical features, joint ranges of motion (ROM), limb and thorax circumferences, weight and creatine kinase (CK) levels were assessed in 11 dogs with GRMD. Alterations of physical features were higher at 13 months, and different disease progression rates were observed. Passive ROM decreased until 1 year old, which was followed by a decline of elbow and tarsal ROM. Limb and thorax circumferences, which were corrected for body weight, decreased significantly between T0 and T3. These measurements can be used to evaluate disease progression in dogs with GRMD and to help discover new therapies for DMD patients.     

Development of a snapback method of single-strand conformation polymorphism analysis for genotyping Golden Retrievers for the X-linked muscular dystrophy allele.

OBJECTIVE: To develop a snapback method of single-strand conformation polymorphism (SSCP) analysis for genotyping Golden Retrievers for the X-linked muscular dystrophy allele. ANIMALS: 20 Golden Retriever puppies from a colony with X-linked muscular dystrophy. PROCEDURE: DNA spanning the canine dystrophin mutation was amplified by means of a polymerase chain reaction (PCR), using a primer modified to have an additional sequence at the 5' terminus. The primer was designed so that 1 terminus of the single-stranded PCR product could anneal to the normal sequence flanking the region of the mutation in the allele but not in the mutant allele. True disease status of the dogs was determined by means of a PCR and restriction digest protocol. RESULTS: Snapback SSCP analysis allowed for accurate and unambiguous genotyping of unaffected, carrier, and affected dogs, whereas conventional SSCP analysis, using the unmodified primer, did not. Creatine kinase activities measured within 24 hours after birth were not consistent with genotype. CONCLUSION AND CLINICAL RELEVANCE: Snapback SSCP analysis provided a simple, fast, and accurate method for genotyping Golden Retrievers for the mutation known to cause X-linked muscular dystrophy.     

Congenital Esophageal Hiatal Hernia in the Chinese Shar-Pei Dog

Esophageal hiatal hernia was diagnosed in 11 young Chinese Shar-Pei dogs between October 1985 and July 1991. The dogs ranged in age from 2 to 11 months and included 3 females and 8 males. The most common clinical signs were regurgitation, vomiting, and hypersalivation. Physical examination was normal in 6 dogs; abnormal physical examination findings in the other 5 dogs included fever, dehydration, hypersalivation, and pulmonary wheezes and crackles. Laboratory evaluation was significant only for neutrophilia in 5 dogs. A diagnosis of hiatal hernia was made on the basis of survey thoracic radio-graphic and/or barium esophagram findings of displacement of the esophagogastric junction and stomach into the thoracic cavity; the diagnosis was confirmed by surgery in 9 dogs and at necropsy in 2 dogs. Megaesophagus (n = 7), gastroesophageal reflux (n = 4), and esophageal hypomotility (n = 1) were additional findings in some dogs. Aspiration pneumonia was diagnosed in 7 of the dogs. Medical therapies formulated for the therapy of presumed reflux esophagitis generally failed to resolve the clinical signs associated with the hiatal hernia. Hiatal herniae were surgically repaired in 9 of the Shar-Peis by various combinations of diaphragmatic crural apposition, fixation of the esophagus to the diaphragmatic crus (esophagopexy), and left fundic tube gastropexy. Eight of the animals survived surgery, six of which have been asymptomatic since surgery (19 to 36 months). The megaesophagus, esophageal hypomotility, and bronchopneumonia resolved in all of these dogs. (Journal of Veterinary Internal Medicine 1993; 7:210–215. Copyright © 1993 by the American College of Veterinary Internal Medicine.)     

Muscular dystrophy in dogs: does the crossing of breeds influence disease phenotype?

Golden Retriever (GR) muscular dystrophy is an inherited degenerative muscle disease that provides an excellent model for Duchenne muscular dystrophy in humans. This study defined the histopathologic lesions, including the distribution of type I and II muscle fibers (FTI and FTII), in 12 dystrophic and 3 nondystrophic dogs between 7 and 15 months of age. The authors were interested in studying the influence on disease phenotype from crossing the base GR breed with Yellow Labrador Retrievers. The dystrophic dogs were divided according to breed: GRs and Golden Labrador Retrievers (GLRs). On hematoxylin and eosin staining, histopathologic lesions were more severe in GRs than GLRs. Six of eight GR muscles (75%) had a severe lesion grade (grade 3). In contrast, seven GLR muscles (87.5%) had mild lesions (grade 2), and only one had severe lesions (grade 3). Changes in fiber-type distribution were more pronounced in GRs versus GLRs. FTI:FTII ratio inversion was observed in three dystrophic GRs but only one GLR. The mean diameter of FTI and FTII was smaller in GRs and GLRs than in nondystrophic dogs (P < .01). The FTI of five GR muscles (62.5%) were larger than those of GLRs, whereas only one GLR muscle was larger (P < .05). The differential was less pronounced for FTII, with four GR muscles being larger and three GLR being larger. Observations indicate that crossing the base GR breed with Labrador Retrievers lessened the severity of the GR muscular dystrophy phenotype.     

Tissue Doppler assessment of diastolic and systolic alterations of radial and longitudinal left ventricular motions in Golden Retrievers during the preclinical phase of cardiomyopathy associated with muscular dystrophy

OBJECTIVE: To quantify radial and longitudinal left ventricular free wall (LVFW) velocities in dogs during the preclinical phase of Golden Retriever muscular dystrophy (GRMD)-associated cardiomyopathy by use of tissue Doppler imaging (TDI). ANIMALS: 9 dogs with GRMD and 6 healthy control dogs. PROCEDURE: All dogs (< 3 years old) were examined via conventional echocardiography and 2-dimensional color TDI. Myocardial velocities in the LVFW were recorded from right parasternal ventricular short-axis (radial motion) and left apical 4-chamber (longitudinal motion) views. Cardiac assessments via TDI included maximal systolic and early and late diastolic LVFW velocities in the endocardial and epicardial layers (for radial motion) and in the basal and apical segments (for longitudinal motion) (for longitudinal motion), RESULTS:-No notable ventricular dilatation or alteration of inotropism was detected in dogs with GRMD via conventional echocardiography. Compared with healthy dogs, endocardial velocities were significantly decreased in dogs with GRMD, resulting in marked decreases in radial myocardial velocity gradients during systole and early and late diastole. Similarly, basal and apical velocities were significantly decreased in systole and the former also in early diastole, resulting in significant decreases in the 2 corresponding longitudinal myocardial velocity gradients. The radial epicardial and longitudinal late diastolic velocities were comparable in the 2 groups. CONCLUSION AND CLINICAL RELEVANCE: Results indicated that GRMD-associated cardiomyopathy in dogs is associated with early marked dysfunction of both radial and longitudinal LVFW motions. These combined regional myocardial abnormalities might be useful criteria for detection of dilated cardiomyopathy at the preclinical stage of the disease in dogs.     

Dystrophin‐deficient muscular dystrophy in two lurcher siblings

Two cases of dystrophin‐deficient muscular dystrophy in 16‐week‐old male lurcher siblings are reported. The myopathies were characterised by regurgitation, progressive weakness and muscle wastage. The dogs had generalised weakness in all four limbs, with more pronounced weakness in the pelvic limbs. Reduced withdrawal in all limbs, muscle contracture and lingual hypertrophy were noted. Serum creatine kinase activities were markedly elevated. Electromyographic abnormalities included fibrillation potentials. Histopathological and immunohistochemical staining were consistent with dystrophin‐deficient muscular dystrophy. Clinical improvement was noted in one of the cases with l ‐carnitine supplementation and supportive therapy. Genetic transmission of the disease was postulated as the dogs were siblings.     

Evaluation of a short interspersed nucleotide element in the 3' untranslated region of the defective dystrophin gene of dogs with muscular dystrophy.

OBJECTIVES: To determine the distribution of a 231-base pair (bp) element in the dystrophin gene 3' untranslated region (UTR) in a colony of Golden Retrievers with muscular dystrophy and other unrelated dogs and to estimate the frequency of recombination for the canine dystrophin gene. ANIMALS: 77 dogs from the Golden Retriever Muscular Dystrophy (GRMD) colony at the Murdoch Veterinary School and 30 unrelated dogs from the Murdoch University Veterinary Clinic. PROCEDURE: Samples of blood or hair from dogs were used for amplification of DNA, using primers to the canine dystrophin 3' UTR. RESULTS: The DNA from affected dogs generated a larger PCR product than that obtained from clinically normal dogs. Products were cloned and sequenced, and the difference in size was found to be attributable to a 231-bp short interspersed nucleotide element (SINE). The SINE was found in all affected dogs in the colony but not in most unaffected puppies in the colony. Eighteen of 19 dogs in the colony were heterozygous for the GRMD mutation, and 7 of 30 unrelated dogs also were heterozygous for the SINE. CONCLUSION AND CLINICAL RELEVANCE: Evidence of recombination between the GRMD mutation and the SINE was observed in only 4 dogs (2 sets of littermates) in the GRMD colony. Incidence of this SINE in a few unrelated dogs suggests that this particular insertion into the dystrophin gene may have been a recent event. The SINE in the dystrophin 3' UTR did not have an apparent influence on dystrophin mRNA concentrations.     

Golden Retriever uveitis: 75 cases (1994-1999)

OBJECTIVE: To document the presenting ocular signs and the clinical course of Golden Retriever dogs with a progressive anterior uveitis, often associated with the histologic presence of iridociliary cysts. Animals studied Seventy-five Golden Retriever dogs (142 affected eyes) referred to a private practice referral ophthalmology clinic between 1994 and 1999. Procedures Complete ophthalmic evaluation with slit-lamp biomicroscopy, indirect ophthalmoscopy, applanation tonometry, and gonioscopy. Hematology, serum biochemical evaluations, and serologic titers for endemic infectious agents were also used in selected cases. RESULTS: The age range of affected dogs was 4.5-14.5 years, with a mean age of 8.6 +/- 2.1 years. The majority of the dogs (n = 66) were affected in both eyes at first presentation. The sex distribution included 4 intact males, 32 neutered males, and 39 spayed females. Hematology, serum biochemical evaluations, and serologic titers for endemic infectious agents failed to demonstrate any underlying disorder. The ophthalmic hallmark of this syndrome was the appearance of pigment on the anterior lens capsule, often in a radial orientation. This capsular pigment was seen both with and without associated uveal cysts. Although single to multiple iridociliary cysts were noted clinically in only 13.3% of the cases, cysts were common on histopathology of advanced glaucomatous, blind eyes. Fibrin was observed in the anterior chamber of 37% of the cases, and often was a precursor for glaucoma. Cataract formation (37%) and glaucoma (46%) were frequent sequelae to the uveitis. Posterior synechiae formation occurred in 50% of the cases. Histopathologic analysis of four enucleated eyes and the eviscerated specimens from 14 glaucomatous eyes demonstrated thin-walled iridociliary epithelial cysts in 3/4 and 12/14 cases, respectively. Microscopically, little to no uveal inflammatory infiltration was commonly noted. Conclusion The overall prognosis for this progressive uveitis in Golden Retriever dogs is guarded, with 46% of the eyes becoming blind due to glaucoma. Iridociliary cysts in Golden Retriever dogs may lead to the development of glaucoma in this breed.     

Aneurysmal dilatation of the right auricle in two dogs

An 8-year-old sexually intact male Golden Retriever with a history of collapse during exercise underwent an examination during which tachydysrhythmia was identified. At another institution, a 12.5-year-old spayed female Lhasa Apso was referred because of a cough and for evaluation of a heart murmur. In the Golden Retriever, radiographic examination revealed bulging of the craniodorsal aspect of the cardiac silhouette and echocardiography revealed right atrial dilatation. In the Lhasa Apso, a cranial mediastinal mass was suspected on the basis of radiographic findings, but no abnormalities were detected echocardiographically. In both dogs, nonselective angiography and contrast-enhanced computed tomography revealed a markedly enlarged, thin-walled right auricle. Exploratory thoracotomy in the Golden Retriever revealed a defect in the pericardium through which the right auricle and part of the atrium had herniated. In dogs, a right auricular aneurysm should be considered in differential diagnoses of a cranial mediastinal mass (detected radiographically) adjacent to the cardiac silhouette.     

Hiatal Hernia Repair by Restoration and Stabilization of Normal Anatomy An Evaluation in Four Dogs and One Cat

Clinical signs of esophageal hiatal hernia in four dogs and one cat included regurgitation, vomiting, hematemesis, hypersalivation, dysphagia, and dyspnea. Thoracic radiographs, esophagram, and fluoroscopy were used to demonstrate cranial displacement of the esophagogastric junction and part of the stomach through the esophageal hiatus. Other findings included megaesophagus, esophageal hypomotility, gastroesophageal reflux, and pneumonia. Medical therapy failed to resolve the clinical signs. Reduction in size of the esophageal hiatus, fixation of the esophagus to the diaphragmatic crus (esophagopexy), and a left fundic gastropexy were performed. Surgical results were considered good to excellent.     

Cerebrospinal Fluid Analysis and Clinical Outcome of Eight Dogs With Eosinophilic Meningoencephalomyelitis

Eight dogs, 14 weeks to 5.5 years of age, had signs of diffuse or multifocal meningoencephalomyelitis. The total white cell counts of the cerebrospinal fluid (CSF) ranged from 11 to 5,550 cells/microliters; the percentage of eosinophils ranged from 21% to 98%. The total CSF protein content range was 19 to 1,430 mg/dl. On necropsy, two dogs had granulomatous encephalomyelitis due to protozoan infection. The other six dogs, of which three were Golden Retriever dogs, appeared to have an idiopathic eosinophilic meningoencephalitis; four of these dogs recovered. The significance of eosinophils in CSF and the possible emergence of a new encephalitic syndrome of dogs involving a hypersensitivity to an unknown agent is also discussed.     

Dystrophin-deficient muscular dystrophy in a Toy Poodle with a single base pair insertion in exon 45 of the Duchenne muscular dystrophy gene

A 10-month-old, intact male Toy Poodle was referred for a postural abnormality. Blood biochemical tests revealed a marked increase in plasma creatine phosphokinase (CPK) concentration. The isoenzyme test showed that 99% of serum CPK consisted of CPK-MM. Histopathological evaluation of muscle biopsy samples confirmed scattered degeneration and necrosis of myofibers. Immunohistochemistry for dystrophin showed an absence of staining in muscle cells. Based on these findings, the dog was diagnosed with dystrophin-deficient muscular dystrophy. Whole genome sequencing using genomic DNA extracted from blood revealed a single base pair insertion in exon 45 of the Duchenne muscular dystrophy (DMD) gene. This is the first report on muscular dystrophy in Toy Poodles and identified a novel mutation in the DMD gene.     

Prevalence of thyroglobulin autoantibodies detected by enzyme-linked immunosorbent assay of canine serum in hypothyroid, obese and healthy dogs in Japan

Thyroglobulin autoantibodies (TgAA) were detected in sera of hypothyroid (n=19), obese (n=28) and clinically healthy dogs (n=52) using a commercially available immunoassay kit. TgAA-positive results occurred in 10 of 19 hypothyroid, 1 of 28 obese and 1 of 52 clinically healthy dogs. The clinically healthy TgAA-positive dog had additional evidence of hypothyroidism supported by low total T(4), low free T(4) and high canine TSH. Among the breeds, Golden Retriever had the highest frequency of hypothyroid (9/19) and TgAA-positive hypothyroid dogs (6/10). This study was the first survey about the prevalence of canine TgAA in Japan and could be a useful reference for clinicians.     

SUBCLINICAL CT ABNORMALITIES IN THE LUMBOSACRAL SPINE OF OLDER LARGE-BREED DOGS

Computed tomography (CT) of the L5-S3 vertebral levels was performed in six, large-breed dogs presented for problems unrelated to the lumbosacral spine. All dogs were asymptomatic for lumbosacral stenosis on neurologic examination. Breeds included German Shepherd, Golden Retriever, Boxermix and Belgian Malinois. Ages ranged from 5-12 years. Five out of six dogs exhibited CT abnormalities. Among the 18 disc levels examined, the most common findings were idiopathic stenosis, loss of vertebral canal epidural fat, and nerve tissue displacement. Less common abnormalities were vertebral canal or foraminal bone proliferation, loss of intervertebral foramen fat, vertebral canal disc bulging, degenerative articular process joint disease, transitional vertebra, dural ossification, foraminal disc bulging, Schmorl's nodes, calcified extruded disc fragment, and sacroiliac joint osteophytes. Vertebral subluxation was absent in all dogs. Findings indicate that some lumbosacral CT abnormalities may be clinically insignificant, especially in older dogs.     

Hereditary spectrin deficiency in Golden Retriever dogs

Spectrin deficiency with increased erythrocyte osmotic fragility (OF) is a hallmark of hereditary spherocytosis, which is the most common congenital hemolytic anemia in humans of northern European ancestry. A radioimmunoassay revealed that erythrocyte spectrin concentration was 50-65% of normal in 5 adult Golden Retriever dogs, which had recovered from hemolytic anemia but whose OF had persistently remained increased. OF also was increased and spectrin concentration was decreased (60-73%) in 10 dogs of an apparently healthy family of 19 Golden Retrievers related to a proband. Pedigree analysis revealed autosomal dominant inheritance. In addition, OF was increased in 23 (17%) of 134 randomly chosen Golden Retrievers with nonhematologic diseases. In these Golden Retrievers, the spectrin concentration was decreased in 5 dogs with increased OF and within the reference range in 6 dogs with normal OF, indicating that in this population spectrin deficiency and increased OF are highly associated (P < .002). Considering these patients a representative sample of the Golden Retriever population in the Netherlands, spectrin deficiency may occur in 11.2-24.6% of Dutch Golden Retrievers (confidence level = 0.95). In blood smears, spherocytes were recognized only in dogs with immune-mediated anemia. At scanning electron microscopy, blood from spectrin-deficient Golden Retrievers showed slight crenation when fixed freshly but abundant echinospherocytes after 24 hours of incubation. We conclude that occult autosomal dominant spectrin deficiency occurs in dogs and is frequent in Dutch Golden Retrievers. It is not clear whether spectrin deficiency in Golden Retrievers may result in hemolytic anemia, as in humans.     

Cytology of canine malignant histiocytosis

Cytologic features of bone marrow, tissue, and abdominal fluid in seven cases of malignant histiocytosis in dogs are described, and histopathology, hematology, and serum biochemistry of the cases are reviewed. Diagnosis of malignant histiocytosis was confirmed by tissue morphology and immunohistochemistry; neoplastic cells in all cases had positive immunoreactivity to lysozyme. This stain can be used to definitively establish the diagnosis of malignant histiocytosis on cytology specimens as well as tissue sections. Cytologic findings included numerous pleomorphic, large, discrete mononuclear cells with abundant, lightly basophilic, vacuolated, granular cytoplasm. Nuclei were round to oval to reniform with marked anisocytosis and anisokaryosis; nucleoli were prominent. Mitotic figures, often bizarre, were occasionally seen. Multinucleated giant cells and phagocytosis of erythrocytes and leukocytes were prominent features in cytologic preparations in four cases. Four dogs were anemic, five dogs were thrombocytopenic, and three dogs were hypercalcemic. Breeds affected included Doberman Pinscher (1), Golden Retriever (2), Flat Coated Retriever (3), and mixed-breed dog (1).