Golden Retriever Muscular Dystrophy

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Grade II dystrophy in a Golden Retriever showing advanced muscular atrophy[1]

Golden Retriever muscular dystrophy (GRMD) is a rare genetic disease of Golden Retriever dogs characterized by reduced muscle dystrophin.

Dystrophin is a vital cytoplasmic protein that connects the cytoskeleton of a muscle fiber to the surrounding extracellular matrix through the cell membrane.

GRMD is an X-linked dystrophy similar to Duchenne muscular dystrophy, but the underlying aberration is thought to be initiated by a reduced release of growth hormone in the pars distalis of the adenohypophysis, resulting in reduced effectiveness of transforming growth factor-β1 cytokines and consequent poor dystrophin development within skeletal muscle[2]. In GRMD dogs, growth factor-β1 is significantly elevated in dogs up to 60 days of age[3], implication its role in the pathogenesis of disease.

As with Duchenne muscular dystrophy, there is characteristic muscular atrophy observed. Milder phenotypes, some showing no clinical signs, may be due to a modifier gene most likely inherited through male-to-male transmission[4][1].

Clinically affected dogs commonly present at 3 - 4 months of age with poor weight gain, tarsal overflexion (cow hocks) hypoglycemia, generalized weakness, cardiac abnormalities such as atrial standstill (occult cardiomyopathy)[5], skeletal muscle atrophy and pelvic limb weakness[6]. Physical disease is usually graded I - III depending on extent of muscular atrophy. Many grade III cases terminate in extreme cachexia, sepsis and death at 6 - 12 months of age.

Diagnosis is based on muscle biopsy, usually the vastus lateralis muscle, 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 often elevated and there may be a mild eosinophilia.

A differential diagnosis would include polymyositis, nemaline myopathy, Duchenne muscular dystrophy[7], Toxoplasma gondii, Hepatozoon americanum, Sarcocystis neurona[8], Neospora spp[9], Hammondia hammondi, masticatory muscle myositis, tetanus, myasthenia gravis[10], thymoma[11] and dermatomyositis.

The use of prednisolone may benefit affected dogs in the short-term, but has been shown to promote disease progression[12]. Adjunct therapy such as hematopoietic stem cell transplantation does not appear to improve clinical progress[13].

Feeding of Grade III pups is difficult because of tongue hypertrophy and transient megaesophagus, resulting in suckling difficulties. Supplementation with a replacement milk product for puppies is usually done through an orogastric tube. Some pups will show clinical improvement and eventually gain weight and prosper to a degree.

Although there is no remedial treatment for this disease, adeno-associated viral (AAV) vector-mediated gene replacement strategies hold promise as a treatment[14].


  1. 1.0 1.1 Ambrósio CE et al (2009) Identification of three distinguishable phenotypes in golden retriever muscular dystrophy. Genet Mol Res 8(2):389-396
  2. de Lima AR et al (2007) Muscular dystrophy-related quantitative and chemical changes in adenohypophysis GH-cells in golden retrievers. Growth Horm IGF Res 17(6):480-491
  3. Passerini L et al (2002) Fibrogenic cytokines and extent of fibrosis in muscle of dogs with X-linked golden retriever muscular dystrophy. Neuromuscul Disord 12(9):828-835
  4. Ambrósio CE et al (2008) Ringo, a Golden Retriever Muscular Dystrophy (GRMD) dog with absent dystrophin but normal strength. Neuromuscul Disord 18(11):892-893
  5. Chetboul V et al (2004) Diagnostic potential of natriuretic peptides in the occult phase of golden retriever muscular dystrophy cardiomyopathy. J Vet Intern Med 18(6):845-850
  6. Marsh AP et al (2010) Kinematics of gait in golden retriever muscular dystrophy. Neuromuscul Disord 20(1):16-20
  7. Thibaud JL et al (2012) Comprehensive longitudinal characterization of canine muscular dystrophy by serial NMR imaging of GRMD dogs. Neuromuscul Disord 22(2):S85-S99
  8. Vashisht K et al (2005) Naturally occurring Sarcocystis neurona-like infection in a dog with myositis. Vet Parasitol 133(1):19-25
  9. Reichel MP et al (2007) Neosporosis and hammondiosis in dogs. J Small Anim Pract 48(6):308-312
  10. Clooten JK et al (2003) Myasthenia gravis and masticatory muscle myositis in a dog. Can Vet J 44(6):480-483
  11. Hackett TB et al (1995) Third degree atrioventricular block and acquired myasthenia gravis in four dogs. J Am Vet Med Assoc 206:1173–1176
  12. Liu JM et al (2004) Effects of prednisone in canine muscular dystrophy. Muscle Nerve 30(6):767-773
  13. Dell'Agnola C et al (2004) Hematopoietic stem cell transplantation does not restore dystrophin expression in Duchenne muscular dystrophy dogs. Blood 104(13):4311-4318
  14. Wang Z et al (2012) Successful regional delivery and long-term expression of a dystrophin gene in canine muscular dystrophy: a preclinical model for human therapies. Mol Ther 20(8):1501-1507