Congenital Myasthenic Syndrome (CMS) in Golden Retrievers
Congenital myasthenic syndrome is a group of inherited neuromuscular disorders that are characterized by progressive muscle weakening that worsens with exercise.
Phenotype: Progressive muscular weakening of dogs is first evident at 6-8 weeks of age. Affected dogs often have a choppy gait with a progressive stiffening of the legs during ambulation. Exercise exacerbates the symptoms.
Breeds appropriate for testing: Golden Retriever and Golden Retriever crosses
Explanation of Results:
Dogs with N/N genotype do not have the variant associated with congenital myasthenic syndrome found in Golden Retrievers.
Dogs with N/CMS genotype are carriers of the congenital myasthenic syndrome variant found in Golden Retrievers but will not develop congenital myasthenic syndrome. If two carriers are mated, approximately 25% of the puppies are predicted to develop disease and 50% are predicted to be carriers.
Dogs with CMS/CMS genotype are homozygous for the congenital myasthenic syndrome variant found in Golden Retrievers and are expected to develop this progressive neuromuscular disease.
Dogs affected with congenital myasthenic syndrome (CMS) demonstrate generalized muscle weakness with symptoms becoming evident at 6-8 weeks after birth. The symptoms of CMS are often exacerbated with exercise. The gait of affected pups has been described as choppy with increasingly short strides and stiffening of the legs. Unlike myasthenia gravis (another neuromuscular condition), megaesophagous (loss of motility of the esophagus) is not evident.
A variant in the collagen‐like tail of the asymmetric acetylcholinesterase gene (COLQ) was identified as the likely cause for congenital myasthenic syndrome (CMS) seen in Golden Retrievers. This variant, c.880G>A, is predicted to result in a change in the functional product of this gene by altering the protein sequence from glycine to arginine at amino acid position 294(p.G294R). Muscle biopsies from an affected litter of puppies (four puppies in total) homozygous for this variant lacked normal gene product. While the precise functional effect of this mutation has not been determined, the protein product is responsible for clearing acetylcholine from the neuromuscular junction thus enabling the successful ending of a muscle contraction. It is hypothesized that this variant affects the normal gene product through one of multiple mechanisms and thus acetylcholine cannot be cleared from the neuromuscular junction and this leads to muscle fatigue.
Congenital myasthenic syndrome in the Golden Retriever is inherited in an autosomal recessive fashion. Two copies of the variant must be present for the disease to manifest, and both sexes are equally affected.
In the initial study that identified the causal genetic variant, researchers did not find this variant in other Golden Retrievers, suggesting that it may be limited to a specific line or is at very low frequency in the population. Research to investigate the allele frequency in the Golden Retriever population is on-going at the VGL. Testing for this variant can assist veterinarians with diagnosis and helps breeders identify carriers among breeding stock to select appropriate mates that will reduce the risk of producing affected offspring. To avoid the possibility of producing affected puppies, matings between known carriers should be avoided. Dogs who genotype CMS/CMS should be clinically evaluated.
Note: This test is specific for the autosomal recessive COLQ variant present in the Golden Retriever. This assay does not detect the COLQ variants in Labrador Retrievers.
At least 15 business days; may be delayed beyond 15 business days if sample requires additional testing, or a new sample is requested.