Precision medicine using whole genome sequencing identifies a novel dystrophin (DMD) variant for X-linked muscular dystrophy in a cat.

BACKGROUND: Muscular dystrophies (MDs) are a large, heterogeneous group of degenerative muscle diseases. X-linked dystrophin-deficient MD in cats is the first genetically characterized cat model for a human disease and a few novel forms have been identified. HYPOTHESIS/OBJECTIVES: Muscular dystrophy was suspected in a young male domestic shorthair cat. Clinical, molecular, and genetic techniques could provide a definitive diagnosis. ANIMALS: A 1-year-old male domestic shorthair cat presented for progressive difficulty walking, macroglossia and dysphagia beginning at 6 months of age. The tongue was thickened, protruded with constant ptyalism, and thickening and rigidity of the neck and shoulders were observed. METHODS: A complete neurological examination, baseline laboratory evaluation and biopsies of the trapezius muscle were performed with owner consent. Indirect immunofluorescence staining of muscle cryosections was performed using several monoclonal and polyclonal antibodies against dystrophy-associated proteins. DNA was isolated for genomic analyses by whole genome sequencing and comparison to DNA variants in the 99 Lives Cat Genome Sequencing dataset. RESULTS AND CLINICAL IMPORTANCE: Aspartate aminotransferase (687 IU/L) and creatine kinase (24 830 IU/L) activities were increased and mild hypokalemia (3.7 mmol/L) was present. Biopsy samples from the trapezius muscle confirmed a degenerative and regenerative myopathy and protein alterations identified by immunohistochemistry resulted in a diagnosis of a in dystrophin-deficient form of X-linked MD. A stop gain variant (c.4849C>T; p.Gln1617Ter) dystrophin was identified by genome sequencing. Precision/genomic medicine efforts for the domestic cat and in veterinary medicine support disease variant and animal model discovery and provide opportunities for targeted treatments for companion animals.

Combination HSCT and intravenous AAV-mediated gene therapy in a canine model proves pivotal for translation of Krabbe disease therapy.

Hematopoietic stem cell transplantation (HSCT) is the only approved treatment for presymptomatic infantile globoid cell leukodystrophy (GLD [Krabbe disease]). However, correction of disease is not complete, and outcomes remain poor. Herein we evaluated HSCT, intravenous (IV) adeno-associated virus rh10 vector (AAVrh10) gene therapy, and combination HSCT + IV AAVrh10 in the canine model of GLD. While HSCT alone resulted in no increase in survival as compared with untreated GLD dogs (∼16 weeks of age), combination HSCT + IV AAVrh10 at a dose of 4E13 genome copies (gc)/kg resulted in delayed disease progression and increased survival beyond 1 year of age. A 5-fold increase in AAVrh10 dose to 2E14 gc/kg, in combination with HSCT, normalized neurological dysfunction up to 2 years of age. IV AAVrh10 alone resulted in an average survival to 41.2 weeks of age. In the peripheral nervous system, IV AAVrh10 alone or in addition to HSCT normalized nerve conduction velocity, improved ultrastructure, and normalized GALC enzyme activity and psychosine concentration. In the central nervous system, only combination therapy at the highest dose was able to restore galactosylceramidase activity and psychosine concentrations to within the normal range. These data have now guided clinical translation of systemic AAV gene therapy as an addition to HSCT (NCT04693598, NCT05739643).

Novel COL6A3 frameshift variant in American Staffordshire Terrier dogs with Ullrich-like congenital muscular dystrophy.

Two (male and female) 10-month-old American Staffordshire Terrier littermates presented for progressive weakness, joint contracture, and distal limb joint hyperlaxity beginning around 6 months of age. Neurological examination, serum creatine kinase activity, infectious disease titers, cerebrospinal fluid analysis, and electrodiagnostic testing were performed. Muscle biopsies were collected for histopathology and immunofluorescence staining for localization of dystrophy associated proteins. Whole-genome sequencing (WGS) was performed on 1 affected dog. Variants were compared to a database of 671 unaffected dogs of multiple breeds. Histopathology confirmed a dystrophic phenotype and immunofluorescence staining of muscle cryosections revealed an absence of staining for collagen-6. WGS identified a homozygous 1 bp deletion in the COL6A3 gene, unique to the first affected dog. Sanger sequencing confirmed the homozygous presence of the frameshift variant in both affected dogs. This report describes the clinical features and most likely genetic basis of an Ullrich-like recessively inherited form of congenital muscular dystrophy in American Staffordshire Terriers.

Congenital muscular dystrophy in a dog with a LAMA2 gene deletion.

A 2-year-old female spayed dog was presented with a chronic history of short-strided gait and inability to completely open the jaw. Clinical signs were present since the dog was adopted from a humane society at a few months of age. Serum creatine kinase activity was abnormally high. Neurological examination, electromyography, muscle biopsies with immunofluorescent staining, and whole genome sequencing (WGS) were performed. A dystrophic phenotype was identified histologically in muscle biopsies, deficiency of laminin α2 protein was confirmed by immunofluorescent staining, and a deletion in the LAMA2 gene was identified by analysis of the WGS data. Congenital muscular dystrophy associated with a disease variant in LAMA2 was identified.

Progressive increases in creatine kinase activity in an anorexic cat with necrotising myopathy.

CASE SUMMARY: A 5-year-old castrated male domestic shorthair cat with weight loss and reduced appetite was evaluated for increased and progressively rising creatine kinase (CK) activity. The cat had recently been diagnosed with hepatic lipidosis. Muscle biopsy and histopathology revealed mild myonecrosis and phagocytosis without obvious inflammatory cell infiltrates. Resolution of necrotising myopathy was observed after a short course of anti-inflammatory prednisolone and nutritional supplementation. RELEVANCE AND NOVEL INFORMATION: This is the first report of a necrotising myopathy in a cat associated with progressively increasing CK activity and decreased appetite. Anorexia in cats has been associated with increased CK activity, but an underlying cause of this CK elevation has only been postulated. Here we document muscle necrosis and muscle stiffness in a cat with anorexia.

Congenital dyserythropoiesis and polymyopathy without cardiac disease in male Labrador retriever littermates.

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.

Clinical features and outcome of acquired myasthenia gravis in 94 dogs.

BACKGROUND: Factors known to be associated with outcome of acquired myasthenia gravis (MG) in dogs are limited. HYPOTHESIS/OBJECTIVES: Of dogs with MG, advancing age and comorbid neoplasia are associated with poor long-term prognosis and low rates of remission. ANIMALS: Ninety-four client-owned dogs with MG diagnosed by acetylcholine receptor antibody (AChR Ab) assay between 2001 and 2019 from a university clinic and 3 private clinics in the United States. METHODS: Cases were retrospectively evaluated and data were collected to determine clinical signs, treatment, and response to therapy defined by means of a clinical scoring rubric. Immunological remission was defined as a return of the AChR Ab concentration to <0.6 nmol/L. Multivariable binary logistic regression analysis was used to identify clinical criteria predicting remission. RESULTS: An anticholinesterase drug was used to treat 90/94 (96%) dogs, which in 63/94 (67%) was the sole treatment; other drugs included immune modulators. Clinical remission (lack of clinical signs ≥4 weeks after treatment cessation) was observed in 29 (31% [95% confidence interval (CI): 22.4-40.8%]) dogs, clinical response (lack of clinical signs on treatment) in 14 (15% [95% CI: 9.0-23.6%]) dogs, clinical improvement (on treatment) in 24 (26% [95% CI: 17.8-35.2%]) dogs, and no clinical improvement in 27 (29% [95% CI: 20.5-38.6%]) dogs. Immunological remission was observed in 27/46 (59%) dogs, with clinical remission in all 27. Younger age (P = .04) and comorbid endocrine disease (P = .04) were associated with clinical remission. Initial AChR Ab concentration (P = .02) and regurgitation (P = .04) were negatively associated with clinical remission. CONCLUSIONS AND CLINICAL IMPORTANCE: Clinical remission in MG is less likely in older dogs and dogs presenting with regurgitation or high initial AChR Ab concentration, but more likely in younger dogs and dogs with comorbid endocrine disease.

Sarcoglycan A mutation in miniature dachshund dogs causes limb-girdle muscular dystrophy 2D.

BACKGROUND: A cohort of related miniature dachshund dogs with exercise intolerance, stiff gait, dysphagia, myoglobinuria, and markedly elevated serum creatine kinase activities were identified. METHODS: Muscle biopsy histopathology, immunofluorescence microscopy, and western blotting were combined to identify the specific pathologic phenotype of the myopathy, and whole genome SNP array genotype data and whole genome sequencing were combined to determine its genetic basis. RESULTS: Muscle biopsies were dystrophic. Sarcoglycanopathy, a form of limb-girdle muscular dystrophy, was suspected based on immunostaining and western blotting, where α, ß, and γ-sarcoglycan were all absent or reduced. Genetic mapping and whole genome sequencing identified a premature stop codon mutation in the sarcoglycan A subunit gene (SGCA). Affected dachshunds were confirmed on several continents. CONCLUSIONS: This first SGCA mutation found in dogs adds to the literature of genetic bases of canine muscular dystrophies and their usefulness as comparative models of human disease.

A CNTNAP1 Missense Variant Is Associated with Canine Laryngeal Paralysis and Polyneuropathy.

Laryngeal paralysis associated with a generalized polyneuropathy (LPPN) most commonly exists in geriatric dogs from a variety of large and giant breeds. The purpose of this study was to discover the underlying genetic and molecular mechanisms in a younger-onset form of this neurodegenerative disease seen in two closely related giant dog breeds, the Leonberger and Saint Bernard. Neuropathology of an affected dog from each breed showed variable nerve fiber loss and scattered inappropriately thin myelinated fibers. Using across-breed genome-wide association, haplotype analysis, and whole-genome sequencing, we identified a missense variant in the CNTNAP1 gene (c.2810G>A; p.Gly937Glu) in which homozygotes in both studied breeds are affected. CNTNAP1 encodes a contactin-associated protein important for organization of myelinated axons. The herein described likely pathogenic CNTNAP1 variant occurs in unrelated breeds at variable frequencies. Individual homozygous mutant LPPN-affected Labrador retrievers that were on average four years younger than dogs affected by geriatric onset laryngeal paralysis polyneuropathy could be explained by this variant. Pathologic changes in a Labrador retriever nerve biopsy from a homozygous mutant dog were similar to those of the Leonberger and Saint Bernard. The impact of this variant on health in English bulldogs and Irish terriers, two breeds with higher CNTNAP1 variant allele frequencies, remains unclear. Pathogenic variants in CNTNAP1 have previously been reported in human patients with lethal congenital contracture syndrome and hypomyelinating neuropathy, including vocal cord palsy and severe respiratory distress. This is the first report of contactin-associated LPPN in dogs characterized by a deleterious variant that most likely predates modern breed establishment.

Juvenile-onset motor polyneuropathy in Siberian cats.

BACKGROUND: Polyneuropathies are infrequently described in cats. There is a genetic predisposition in several breeds. OBJECTIVE: To clinically characterize a novel motor polyneuropathy in a family of Siberian cats. ANIMALS: Thirteen closely related Siberian cats, 4 clinically affected and 9 clinically unaffected individuals. METHODS: Retrospective study. Clinical data and pedigree information were obtained from the medical records and breeder. Electrodiagnostic testing and muscle and peripheral nerve biopsy samples were obtained from 1 affected cat. Follow-up information was obtained for all affected cats. RESULTS: Onset of signs was 4 to 10 months in affected cats. Clinical signs were progressive or waxing/waning neuromuscular weakness (4/4), normal sensory function (4/4), and variably decreased withdrawal reflexes (3/4). All cats returned to normal neurologic function within 1 to 4 weeks. All cats had a recurrence of weakness (3/4 had 1 recurrent episode, 1/4 had 3 relapses) from which they recovered fully. In 1 cat, electromyography and motor nerve conduction studies showed multicentric spontaneous activity, normal motor nerve conduction velocity, reduced compound muscle action potential amplitude, and polyphasia. Histologic evaluation of muscle and nerve in that cat showed mild muscle atrophy consistent with recent denervation, endoneurial and perineurial edema, and mild mononuclear cell infiltration within intramuscular nerve branches and a peripheral nerve. Pedigree analysis suggests an autosomal recessive mode of inheritance, although neither a genetically complex/polygenic condition nor an acquired inflammatory polyneuropathy can be ruled-out. CONCLUSIONS AND CLINICAL IMPORTANCE: We describe a motor polyneuropathy in juvenile Siberian cats characterized by self-limiting weakness with potential relapse.

Krabbe disease successfully treated via monotherapy of intrathecal gene therapy.

Globoid cell leukodystrophy (GLD; Krabbe disease) is a progressive, incurable neurodegenerative disease caused by deficient activity of the hydrolytic enzyme galactosylceramidase (GALC). The ensuing cytotoxic accumulation of psychosine results in diffuse central and peripheral nervous system (CNS, PNS) demyelination. Presymptomatic hematopoietic stem cell transplantation (HSCT) is the only treatment for infantile-onset GLD; however, clinical outcomes of HSCT recipients often remain poor, and procedure-related morbidity is high. There are no effective therapies for symptomatic patients. Herein, we demonstrate in the naturally occurring canine model of GLD that presymptomatic monotherapy with intrathecal AAV9 encoding canine GALC administered into the cisterna magna increased GALC enzyme activity, normalized psychosine concentration, improved myelination, and attenuated inflammation in both the CNS and PNS. Moreover, AAV-mediated therapy successfully prevented clinical neurological dysfunction, allowing treated dogs to live beyond 2.5 years of age, more than 7 times longer than untreated dogs. Furthermore, we found that a 5-fold lower dose resulted in an attenuated form of disease, indicating that sufficient dosing is critical. Finally, postsymptomatic therapy with high-dose AAV9 also significantly extended lifespan, signifying a treatment option for patients for whom HSCT is not applicable. If translatable to patients, these findings would improve the outcomes of patients treated either pre- or postsymptomatically.

A mutation in MTM1 causes X-Linked myotubular myopathy in Boykin spaniels.

The purpose of this study was to report the findings of clinical and genetic evaluation of a 3-month old male Boykin spaniel (the proband) that presented with progressive weakness. The puppy underwent a physical and neurological examination, serum biochemistry and complete blood cell count, electrophysiological testing, muscle biopsy and whole genome sequencing. Clinical evaluation revealed generalized neuromuscular weakness with tetraparesis and difficulty holding the head up and a dropped jaw. There was diffuse spontaneous activity on electromyography, most severe in the cervical musculature. Nerve conduction studies were normal, the findings were interpreted as consistent with a myopathy. Skeletal muscle was grossly abnormal on biopsy and there were necklace fibers and abnormal triad structure localization on histopathology, consistent with myotubular myopathy. Whole genome sequencing revealed a premature stop codon in exon 13 of MTM1 (ChrX: 118,903,496 C > T, c.1467C>T, p.Arg512X). The puppy was humanely euthanized at 5 months of age. The puppy's dam was heterozygous for the variant, and 3 male puppies from a subsequent litter all of which died by 2 weeks of age were hemizygous for the variant. This naturally occurring mutation in Boykin spaniels causes a severe form of X-linked myotubular myopathy, comparable to the human counterpart.

Clinical and serologic remission of acquired myasthenia gravis in a domestic ferret (Mustela putorius furo).

CASE DESCRIPTION: A 4.5-year-old neutered male domestic ferret (Mustela putorius furo) was examined because of clinical signs compatible with neuromuscular disease. CLINICAL FINDINGS: Results of electrophysiologic assessment, including measurement of compound muscle action potentials following repetitive nerve stimulation, and measurement of the anti-acetylcholine receptor antibody titer were consistent with a diagnosis of acquired myasthenia gravis. TREATMENT AND OUTCOME: Medical treatment with pyridostigmine and prednisolone was instituted. The first signs of clinical improvement were observed 2 months later, followed by a slow but steady improvement over the next months. Anti-acetylcholine receptor antibody titer was measured 10 months after initiation of treatment and was markedly decreased, compared with the initial titer. Pyridostigmine and prednisolone dosages were tapered over the following 4 months without any evidence of recurrence of clinical signs. Thirty months after initial examination, the ferret was clinically normal and not receiving any treatment. A follow-up anti-acetylcholine receptor antibody titer was similar to previously published values for healthy ferrets. CLINICAL RELEVANCE: Findings indicated that clinical and serologic remission can be achieved in ferrets with myasthenia gravis. However, owner willingness to provide extensive supportive care was vital to the outcome for this patient, as was the owner's decision to not euthanize the ferret despite an initial lack of response to treatment.

Trismus, masticatory myositis and antibodies against type 2M fibers in a mixed breed cat.

CASE SUMMARY: A 1-year-old male neutered mixed breed cat presented with a 2 month history of inability to fully open the mouth when yawning and decreased ability to prehend food. Physical examination revealed severe bilaterally symmetrical masticatory muscle atrophy, a restricted vertical mandibular range of motion of 11-12 mm, and a normal body condition score. Skull radiography was normal. A canine ELISA system against unique masticatory muscle fibers (2M antibody titer), was positive at 1:1000 (reference interval <1:100 in dogs, and was <1:100 using serum from five archived normal cats), indicating the presence of cross-reacting antibodies. Owing to the chronicity and clinical severity, corticosteroid treatment did not result in improved jaw mobility, consistent with end-stage masticatory myositis. Masticatory muscle biopsy was declined at initial presentation. However, 1 year later at elective euthanasia, CT ruled out temporomandibular joint osseous restrictions, and masticatory and biceps femoral muscle histopathology evaluation confirmed end stage feline masticatory myositis with normal limb muscle. RELEVANCE AND NOVEL INFORMATION: Masticatory myositis should be included in the differential diagnosis of trismus in cats. A canine ELISA can be used to indicate the presence of feline 2M cross-reacting antibodies. More cases are needed to fully elucidate the clinical presentation and best course of treatment.

AAVrh10 Gene Therapy Ameliorates Central and Peripheral Nervous System Disease in Canine Globoid Cell Leukodystrophy (Krabbe Disease).

Globoid cell leukodystrophy (GLD), or Krabbe disease, is an inherited, neurologic disorder that results from deficiency of a lysosomal enzyme, galactosylceramidase. Most commonly, deficits of galactosylceramidase result in widespread central and peripheral nervous system demyelination and death in affected infants typically by 2 years of age. Hematopoietic stem-cell transplantation is the current standard of care in children diagnosed prior to symptom onset. However, disease correction is incomplete. Herein, the first adeno-associated virus (AAV) gene therapy experiments are presented in a naturally occurring canine model of GLD that closely recapitulates the clinical disease progression, neuropathological alterations, and biochemical abnormalities observed in human patients. Adapted from studies in twitcher mice, GLD dogs were treated by combination intravenous and intracerebroventricular injections of AAVrh10 to target both the peripheral and central nervous systems. Combination of intravenous and intracerebroventricular AAV gene therapy had a clear dose response and resulted in delayed onset of clinical signs, extended life-span, correction of biochemical defects, and attenuation of neuropathology. For the first time, therapeutic effect has been established in the canine model of GLD by targeting both peripheral and central nervous system impairments with potential clinical implications for GLD patients.

Evaluation of coexisting polymyositis in feline myasthenia gravis: A case series.

Acquired myasthenia gravis (MG) is relatively uncommon in cats. In humans, MG may be associated with other immune-mediated disorders, in particular polymyositis (PM). In this study, we described in-depth electrodiagnostic findings and pathological changes in muscles of cats diagnosed with MG, and assessed the presence of concurrent PM. Six cats with confirmed acetylcholine receptor antibody seropositive MG, and two suspected cases with clinical signs and electrophysiological changes consistent with MG, were reviewed. All animals presented with severe typical signs of generalized weakness and/or fatigability, resembling late-onset MG in humans, in addition to regurgitation. Five cats presented a cranial mediastinal mass, with 3 confirmed as thymoma. Repetitive nerve stimulation revealed a decrement of the compound muscle action potential in all tested cases, starting from low frequencies of stimulation. Serum creatine kinase activity was increased in 6/8 cats. Muscle biopsies performed in 5 cats revealed varying degrees of mixed mononuclear cell infiltrates, positive for the leukocyte markers CD3/CD4/CD8 and CD11b. Further MHC-1/C5b-9 positive sarcolemmal deposits were identified in all tested cases, with or without thymoma. This study documents an association of MG and PM in cats, and provides further support for feline MG as a relevant animal model of human MG.

Association of early onset myasthenia gravis in Newfoundland dogs with the canine major histocompatibility complex class I.

Acquired Myasthenia Gravis (MG) is an autoimmune neuromuscular disorder whose development in humans has been associated with the Major Histocompatibility Complex (MHC) or Human Leukocyte Antigen (HLA). There is a form of early onset MG (EOMG) in Newfoundland dogs that mimics the clinical presentation in humans and appears to have familial inheritance. Genotyping of three classical Dog Leukocyte Antigen (DLA) class II genes, DLA-DRB1, DLA-DQA1 and DLA-DQB1, in 16 Newfoundlands with EOMG and 46 unaffected Newfoundlands, identified DLA-DQB1 *00301 (p-value = 0.0051 OR: 7.41) as a risk locus for the development of EOMG in this breed. In order to further investigate the extent of the association to the entire MHC region, 208 additional SNPs were genotyped in two phases. Both a risk locus for EOMG to the DLA class I (chr12: 458483-506460) and a protective locus for EOMG susceptibility that extends outside of the DLA class I (chr12: 89701-475348) were identified. Four additional dog breeds with an elevated risk for the development of MG were SNP genotyped, but no shared or significant associations were found. MHC involvement in canine MG disease manifestation overlaps with loci identified in human studies and highlights the value of dogs as a model for genetic studies of naturally occurring diseases.

Evaluation of Dogs with Border Collie Collapse, Including Response to Two Standardized Strenuous Exercise Protocols.

Clinical and metabolic variables were evaluated in 13 dogs with border collie collapse (BCC) before, during, and following completion of standardized strenuous exercise protocols. Six dogs participated in a ball-retrieving protocol, and seven dogs participated in a sheep-herding protocol. Findings were compared with 16 normal border collies participating in the same exercise protocols (11 retrieving, five herding). Twelve dogs with BCC developed abnormal mentation and/or an abnormal gait during evaluation. All dogs had post-exercise elevations in rectal temperature, pulse rate, arterial blood pH, PaO2, and lactate, and decreased PaCO2 and bicarbonate, as expected with strenuous exercise, but there were no significant differences between BCC dogs and normal dogs. Electrocardiography demonstrated sinus tachycardia in all dogs following exercise. Needle electromyography was normal, and evaluation of muscle biopsy cryosections using a standard panel of histochemical stains and reactions did not reveal a reason for collapse in 10 dogs with BCC in which these tests were performed. Genetic testing excluded the dynamin-1 related exercise-induced collapse mutation and the V547A malignant hyperthermia mutation as the cause of BCC. Common reasons for exercise intolerance were eliminated. Although a genetic basis is suspected, the cause of collapse in BCC was not determined.

An Inversion Disrupting FAM134B Is Associated with Sensory Neuropathy in the Border Collie Dog Breed.

Sensory neuropathy in the Border Collie is a severe neurological disorder caused by the degeneration of sensory and, to a lesser extent, motor nerve cells with clinical signs starting between 2 and 7 months of age. Using a genome-wide association study approach with three cases and 170 breed matched controls, a suggestive locus for sensory neuropathy was identified that was followed up using a genome sequencing approach. An inversion disrupting the candidate gene FAM134B was identified. Genotyping of additional cases and controls and RNAseq analysis provided strong evidence that the inversion is causal. Evidence of cryptic splicing resulting in novel exon transcription for FAM134B was identified by RNAseq experiments. This investigation demonstrates the identification of a novel sensory neuropathy associated mutation, by mapping using a minimal set of cases and subsequent genome sequencing. Through mutation screening, it should be possible to reduce the frequency of or completely eliminate this debilitating condition from the Border Collie breed population.

Total laryngectomy for management of chronic aspiration pneumonia in a myopathic dog.

A 5-month-old female pit bull terrier dog evaluated for ataxia, progressive regurgitation, and recurrent aspiration pneumonia had markedly elevated creatine kinase activity, non-inflammatory generalized myopathy, and severe esophageal dysmotility. A narrow-field total laryngectomy was performed. The dog is doing well 30 months after surgery, and no longer has episodes of aspiration pneumonia, despite intermittent regurgitation. This case represents the first application of total laryngectomy for the prevention of chronic recurrent aspiration pneumonia in the dog.

Laryngectomie totale pour la gestion d'une pneumonie par aspiration chronique chez un chien myopathique. Une chienne Pit Bull Terrier âgée de 5 mois évaluée pour de l'ataxie, de la régurgitation progressive et une pneumonie par aspiration récurrente présentait une activité de la créatine kinase particulièrement élevée, une myopathie généralisée non inflammatoire et un trouble de motilité de l'œsophage grave. Une laryngectomie totale à champ étroit a été réalisée. La chienne se porte bien 30 mois après la chirurgie et n'a plus d'épisodes de pneumonie par aspiration, malgré une régurgitation intermittente. Ce cas représente la première application d'une laryngectomie totale pour la prévention d'une pneumonie par aspiration chronique récurrente chez un chien.(Traduit par Isabelle Vallières).