Malignant hyperthermia, Quarter Horse

 

Gene: RYR1

Transmission: Autosomal dominant

For an autosomal recessive genetic disease, an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease, but are carrier animals that can pass the mutation on to future generations.  

Mutation: Substitution, RYR1 gene; c.7360 C>G, p.(R2455G), exon46

Medical system: Pharmacogenetics, muscular

Breed: Quarter Horse

Age of onset of symptoms: During anesthesia, associated with stress

Malignant hyperthermia is a pharmacogenetic disease often triggered by halogen anesthesia but also by stress or being overworked. The gene mutation causes a dysfunction of the calcium release channel from the sarcoplasmic reticulum in skeletal muscles. This disorder results in the excessive release of calcium into muscle cells and this causes a hypermetabolic state characterized by an intense rise in body temperature, increased CO2 levels in the blood (hypercapnia), lactic acidosis and muscle rigidity.  Malignant hyperthermia can be lethal. 

 

References:

OMIA link: [0621-9796]

Aleman M, McCue M, Bellone RR. (2025) Allele frequencies and genotypes for the ryanodine receptor 1 variant causing malignant hyperthermia and fatal rhabdomyolysis with hyperthermia in horses. J Vet Intern Med 39:e70081.  [pubmed/40298507]

Finno CJ. (2025) Genetics of muscle disease. Vet Clin North Am Equine Pract 41:17-29. [pubmed/39880731]

Durward-Akhurst SA, Marlowe JL, Schaefer RJ, et al. (2024) Predicted genetic burden and frequency of phenotype-associated variants in the horse. Sci Rep 14:8396.  [pubmed/38600096]

Aleman M, Scalco, R, Malvick J, et al. (2022) Prevalence of genetic mutations in horses with muscle disease from a neuromuscular disease laboratory. J Equine Vet Sci 118:104129.  [pubmed/36150530]

Rosenberg H, Pollock N, Schiemann A, et al. (2015) Malignant hyperthermia: a review. Orphanet J Rare Dis.10:93. [pubmed/26238698]

Aleman M, Nieto JE, Magdesian KG. (2009) Malignant hyperthermia associated with Ryanodine receptor 1 (C7360G) mutation in Quarter Horses. J Vet Intern Med 23:329-334. [pubmed/19220734]

McCue ME, Valberg J, Jackson M, et al. (2009) Polysaccharide storage myopathy phenotype in quarter horse-related breeds is modified by the presence of an RYR1 mutation. Neuromuscul Disord 19:37-43. [pubmed/19056269]

Nieto JE, Aleman M. (2009) A rapid detection method for the Ryanodine receptor 1 (C7360G) mutation in Quarter Horses. J Vet Intern Med 23:619-622. [pubmed/19298609]

Aleman M, Riehl J, Aldridge BM, et al. (2004) Association of a mutation in the ryanodine receptor 1 gene with equine malignant hyperthermia. Muscle Nerve. 30(3):356-365. [pubmed/15318347]