Duchenne muscular dystrophy
Mutations in the causative gene result in a lack of dystrophin at the muscle fiber membrane. Dystrophin is the essential link between the subsarcolemmal cytoskeleton and the extracellular matrix. Disruption of this link results in fiber necrosis and progressive muscle weakness. The muscle is progressively replaced by fibrous or fatty tissue.
Dystrophin-deficient dogs have been reported in many breeds, including the Golden Retriever, Labrador Retriever, German Short-Haired Pointer, Grand Basset Griffon Vendéen, Weimaraner and Corgi. Gene mutations have been determined in several cases.
Clinically affected dogs commonly present with generalized weakness, bradycardia, anorexia, episodic coughing, poor growth, skeletal muscle atrophy and pelvic limb weakness. Brachygnathism, trismus and dysbasia may be observed in some dogs.
Less than half of affected dogs survive beyond 6 weeks of age, and aspiration pneumonia is a common clinical complication.
Most dogs invariably die from degenerative cardiomyopathy, with concurrent nitrous oxide-mediated vascular endothelial dysfunction, yet paradoxically with no significant decrease in cardiac function.
Diagnosis is based on muscle biopsy, which shows characteristic dystrophic muscle pathology with prominent muscle degeneration, necrosis, myofiber size variation and inflammation. Immunohistochemical analysis usually reveals a lack of dystrophin protein. Blood tests are usually unrewarding, although creatinine kinase levels are usually elevated.
A differential diagnosis would include polymyositis, nemaline myopathy, Golden Retriever Muscular Dystrophy, Toxoplasma gondii, Hepatozoon americanum, Sarcocystis neurona, Neospora spp, Hammondia hammondi, masticatory muscle myositis, tetanus, myasthenia gravis, thymoma and dermatomyositis.
The use of prednisolone may benefit affected dogs in the short-term, but has been shown to promote disease progression. Adjunct therapy such as hematopoietic stem cell transplantation does not appear to improve clinical progress.
Although there is no remedial treatment for this disease, adeno-associated viral (AAV) vector-mediated gene replacement strategies hold promise as a treatment.
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