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Congenital Myasthenic Syndrome (CHAT gene, Old Danish Pointing Dog)

Congenital Myasthenic Syndrome (CHAT gene, Old Danish Pointing Dog)

Congenital myasthenic syndrome (CMS) is a rare neuromuscular disorder that causes transient paralysis after exercise. The disease has been linked to a mutation in the CHAT gene, involved in the production of choline acetyltransferase.

Symptoms

The main symptom of SMC is exercise-induced muscle weakness. Dogs can run normally for 5 to 30 minutes, but after this time, their limbs weaken and flex, causing them to fall. Although the symptoms disappear minutes later, they may reappear if exercise continues. Because of this, exercise intolerance and fatigue occur in affected dogs. It should be noted that the disease is not considered to worsen as it progresses.

Disease Management

Lifestyle interventions, such as limiting exercise and adequate rest periods, can regulate exercise intolerance and fatigue. Should your dog exhibit any symptoms, you should see your veterinarian for evaluation.

Genetic basis

This disease follows an autosomal recessive mode of inheritance. Autosomal recessive inheritance means that the dog, regardless of sex, must receive two copies of the mutation or pathogenic variant to be at risk of developing the disease. Both parents of an affected dog must carry at least one copy of the mutation. Animals with only one copy of the mutation are not at increased risk of developing the disease, but may pass the mutation on to future generations. Breeding between dogs carrying genetic variants that can cause disease, even if they do not show symptoms, is not recommended.

Technical report

Depending on the location of the altered protein at the neuromuscular junction, SMC has several subtypes: presynaptic, synaptic, postsynaptic and congenital disorders of protein glycosylation. In this case, the affected gene (CHAT) encodes a protein known as choline acetyltransferase. This enzyme is responsible for producing acetylcholine, which is released at the presynaptic terminal and is essential in muscle movement. Therefore, the congenital myasthenic syndrome discovered in the Old Danish Pointer breed is of the presynaptic subtype. The presence of a mutation in the CHAT gene implicated in the development of this subtype of CMS has been reported. The mutation consists of a substitution of a G for an A in exon 6, leading to the change of a valine for a methionine at position 29 of the protein (p.V29M).

Most affected breeds

Old Danish Pointing Dog

Bibliography

Proschowsky HF, Flagstad A, Cirera S,et al. Identification of a mutation in the CHAT gene of Old Danish Pointing Dogs affected with congenital myasthenic syndrome. J Hered. 2007;98(5):539-43.