Malignant Hyperthermia

Malignant hyperthermia in dogs is a condition that manifests itself as an adverse reaction to certain medications and stressful situations, which is why it is also known as canine stress syndrome. It is most prominent in greyhounds, although it can also affect other breeds.

Symptoms

Malignant hyperthermia in dogs does not cause symptoms until the dog is exposed to certain triggers such as anesthetics and muscle relaxants or stressful situations. Symptoms of the disease are tachycardia, generalized muscle stiffness and hyperthermia and can even result in the death of the animal if the anesthetic used is not discontinued.

Disease Management

When the dog suffers an attack of hyperthermia, an intravenous injection of a muscle relaxant called Dantrolene is required. The dog should be weaned off anesthetics immediately while its temperature is normalized and its breathing is controlled. Malignant hyperthermia, even if treated properly and quickly, can be fatal. It is important to inform your veterinarian if your dog is a carrier of a mutation in the RYR1 gene that may cause a hyperthermia reaction or if he shows any symptoms typical of this condition.

Genetic basis

This disease follows an autosomal dominant mode of inheritance. Autosomal dominant inheritance means that dogs only have to inherit one copy of the mutation or pathogenic variant to be at risk of developing the disease. Each puppy born to a parent carrying one copy of the mutation has a 50% chance of inheriting one copy of the mutation and being at risk for the disease. Breeding between dogs carrying genetic variants that can cause disease is not recommended, even if they do not show symptoms.

Technical report

Malignant hyperthermia is caused by the presence of a single copy of a pathogenic mutation in the RYR1 gene, i.e. it follows an autosomal dominant mode of inheritance. This condition causes severe physical reactions due to certain triggers which can range from a reaction to different drugs (gaseous anesthetics, especially halothane and some muscle relaxants such as succinylcholine) and substances such as caffeine and hops. Physical reactions can also be triggered by intense physical activity or when the dog is stressed. Here we analyzed the c.1643T>C mutation in RYR1 identified in dogs of the Collie, Doberman Pinscher, German Shepherd and Labrador Retriever breeds (Roberts et al., 2001). The RYR1 gene encodes for the sarcoplasmic reticulum calcium release channel, also known as the ryanodine receptor. This receptor plays a fundamental role in calcium release during the excitation-contraction process in skeletal muscle. Alterations in the RYR1 gene that cause hyperthermia cause the RYR1 protein channel to open for a longer than normal interval in the presence of triggering drugs, and excessive calcium outflow into the sarcoplasm or cytoplasm of muscle cells occurs. Elevated resting sarcoplasmic calcium concentrations trigger muscle contraction, accelerated metabolism and hyperthermia.

Most affected breeds

Collie
Doberman Pinscher
English Springer Spaniel
German Shepherd Dog
Greyhound
Labrador Retriever
Pointer
Saint Bernard

Bibliography

Roberts MC, Mickelson JR, Patterson EE,et al. Autosomal dominant canine malignant hyperthermia is caused by a mutation in the gene encoding the skeletal muscle calcium release channel (RYR1). Anesthesiology. 2001 Sep;95(3):716-25.