Test Detail

Pharmacogenetic muscle disorder caused by a variant of the RYR1 gene (ryanodine receptor type 1) in the horse. The altered calcium channel releases calcium in an uncontrolled manner in response to triggers such as halogenated inhalational anaesthetics, stress or intense exercise, producing hyperthermia, muscle rigidity, acidosis and rhabdomyolysis. The episodes are potentially life-threatening if not treated immediately. The test allows the status to be known before anaesthesia or before incorporating the animal into breeding.

Rare disease. Described mainly in the Quarter Horse and derived breeds (Paint, Appaloosa), although the test is offered for all breeds. There are no reliable population frequency figures (limited data).

- During anaesthesia: rapid and progressive hyperthermia, tachycardia, muscle rigidity and hypercapnia/acidosis
- Episodes triggered by stress or exercise with high fever and profuse sweating
- Muscle rigidity and pain, dark urine (myoglobinuria)
- Rhabdomyolysis with marked elevation of CK and AST
- Sudden death in untreated cases

Malignant hyperthermia was first described in humans and later in the pig, always linked to RYR1. In the horse, the first compatible anaesthetic cases were reported in the early 2000s, especially in Quarter Horse lines. In 2004, Aleman and colleagues identified the equine variant C7360G (p.Arg2454Gly) of RYR1 associated with the disease. Later studies (Aleman et al. 2009) confirmed the association in the Quarter Horse and its coexistence with PSSM1 glycogen storage myopathy (GYS1).

- As it is dominant, a single copy of the allele is enough to transmit the risk: do not use affected or mutated animals in breeding
- Test breeding animals from stock lines, especially if there is a history of anaesthetic reactions or tying-up
- Combine the result with the PSSM1 (GYS1) test: double mutants present more severe muscle conditions
- Communicate the result to the veterinarian before any anaesthesia, sedation or castration
- Avoid triggering anaesthetics and stress and extreme exercise management in animals at risk

Differential diagnosis of the episode: heat stroke, rhabdomyolysis due to PSSM, atypical pasture myopathy, anaphylactic reaction and sepsis. In a mutated animal, plan anaesthetic protocols with non-triggering agents and dantrolene available. Elevation of CK/AST and myoglobinuria point to rhabdomyolysis. Remember that a negative test does not rule out myopathy of another origin.

Aleman M et al. 2004. Association of a mutation in the ryanodine receptor 1 gene with equine malignant hyperthermia. Muscle Nerve. PMID: 15318347; Aleman M et al. 2009. Malignant hyperthermia associated with ryanodine receptor 1 (C7360G) mutation in Quarter Horses. J Vet Intern Med. PMID: 19220734; Rosenberg H et al. 2015. Malignant hyperthermia: a review. Orphanet J Rare Dis. PMID: 26238698; OMIA:000621-9796