OMIA:000621-9796 : Malignant hyperthermia in Equus caballus
Categories: Homeostasis / metabolism phene
Links to MONDO diseases: No links.
Mendelian trait/disorder: yes
Mode of inheritance: Autosomal dominant
Considered a defect: yes
Key variant known: yes
Year key variant first reported: 2004
Cross-species summary: A progressive increase in body temperature, muscle rigidity and metabolic acidosis, leading to rapid death.
Species-specific symbol: RYR1, MH
Species-specific description: Malignant hyperthermia (MH) is a potentially life-threatening disorder in horses that can be triggered by halogenated anaesthetics and other non-aesthetic factors that may include exercise, stress, breeding, illnesses, and concurrent myopathies. It has an estimated mortality rate of 34% when halothane anaesthesia is administered (cited by Aleman et al., 2009). MH occurs primarily in Quarter horses, but has been reported in other breeds including Thoroughbred, Appaloosa, Arabian horses, and ponies (Aleman et al., 2004). Horses are generally mature before exhibiting clinical signs.
[IT thanks Hailey Anderson, working under the guidance of Professor Ernie Bailey, for contributions to this entry in April 2022]
History: The first report of the disease in horses occurred in 1975 (cited by Aleman et al., 2004).
A likely causal variant was identified in 2004 (Aleman et al., 2004).
A synergistic relationship between MH and PSSM1 was reported by McCue et al. (2009).
Inheritance: As noted by Aleman et al. (2004), the fact that the two affected animals with which they dealt were heterozygous suggests autosomal dominant inheritance. However, a pedigree analysis has still to be conducted.
Molecular basis: By cloning and sequencing a very likely comparative candidate gene (based on the homologous disorder in other species, especially pigs and humans), Aleman et al. (2004) characterised the molecular basis of this disorder in two affected horses: a base substitution (C7360G) in exon 46 of the RyR1 gene results in an amino-acid substitution (R2454G). This codon is also mutated in two of the five exon-46 RyR1 mutations in humans.
Clinical features: “Mutations in the RYR1 gene cause dysfunction of the calcium release channel of the sarcoplasmic reticulum in skeletal muscle, resulting in excessive release of calcium into the myoplasm and a hypermetabolic state characterized by intense heat, hypercapnia [elevated carbon dioxide (CO2) levels in the blood], lactic acidosis, and, in many cases, death” (Aleman et al., 2004)
Malignant hyperthermia episodes can include signs such as muscle contracture (rigidity), elevated body temperature, elevated heart rate, irregular heart rhythm, excessive sweating, and shallow breathing. Horses with the MH likely causal variant can exhibit more severe clinical symptoms if they also have a PSSM1 mutation (McCue et al., 2009) (see also OMIA 001158-9796 : Polysaccharide storage myopathy/PSSM1/Exertional rhabdomyolysis in Equus caballus).
Genetic testing: Genetic testing for the reported likely causal variant is available.
|Symbol||Description||Species||Chr||Location||OMIA gene details page||Other Links|
|RYR1||ryanodine receptor 1 (skeletal)||Equus caballus||10||NC_009153.3 (9633620..9739087)||RYR1||Homologene, Ensembl , NCBI gene|
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WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.
Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.
|OMIA Variant ID||Breed(s)||Variant Phenotype||Gene||Allele||Type of Variant||Source of Genetic Variant||Reference Sequence||Chr.||g. or m.||c. or n.||p.||Verbal Description||EVA ID||Inferred EVA rsID||Year Published||PubMed ID(s)||Acknowledgements|
|159||Quarter Horse (Horse)||Malignant hyperthermia||RYR1||missense||Naturally occurring variant||EquCab3.0||10||g.9678680C>G||c.7363C>G||p.(R2455G)||XM_023649662.1; XP_023505430.1; published as c.7360C>G and p.(R2454G); coordinates in the table have been updated to a recent reference genome and / or transcript||2004||15318347||The genomic position in EquCab3.0 was provided by Hailey Anderson, working under the guidance of Professor Ernie Bailey in April 2022|
Cite this entry
Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.
|2022||Aleman, M., Scalco, R., Malvick, J., Grahn, R.A., True, A., Bellone, R.R. :|
|Prevalence of genetic mutations in horses with muscle disease from a neuromuscular disease laboratory. J Equine Vet Sci 118:104129, 2022. Pubmed reference: 36150530 . DOI: 10.1016/j.jevs.2022.104129.|
|2009||Aleman, M., Nieto, JE., Magdesian, KG. :|
|Malignant hyperthermia associated with ryanodine receptor 1 (C7360G) mutation in Quarter Horses. J Vet Intern Med 23:329-34, 2009. Pubmed reference: 19220734 . DOI: 10.1111/j.1939-1676.2009.0274.x.|
|McCue, ME., Valberg, SJ., Jackson, M., Borgia, L., Lucio, M., Mickelson, JR. :|
|Polysaccharide storage myopathy phenotype in quarter horse-related breeds is modified by the presence of an RYR1 mutation. Neuromuscul Disord 19:37-43, 2009. Pubmed reference: 19056269 . DOI: 10.1016/j.nmd.2008.10.001.|
|Nieto, JE., Aleman, M. :|
|A rapid detection method for the ryanodine receptor 1 (C7360G) mutation in Quarter Horses. J Vet Intern Med 23:619-222, 2009. Pubmed reference: 19298609 . DOI: 10.1111/j.1939-1676.2009.0281.x.|
|2005||Aleman, M., Brosnan, RJ., Williams, DC., LeCouteur, RA., Imai, A., Tharp, BR., Steffey, EP. :|
|Malignant hyperthermia in a horse anesthetized with halothane. J Vet Intern Med 19:363-6, 2005. Pubmed reference: 15954554 .|
|2004||Aleman, M., Riehl, J., Aldridge, BM., LeCouteur, RA., Stott, JL., Pessah, IN. :|
|Association of a mutation in the ryanodine receptor 1 gene with equine malignant hyperthermia. Muscle Nerve 30:356-65, 2004. Pubmed reference: 15318347 . DOI: 10.1002/mus.20084.|
|1994||Cornick, J.L., Seahorn, T.L., Hartsfield, S.M. :|
|Hyperthermia during isoflurane anaesthesia in a horse with suspected hyperkalaemic periodic paralysis. Equine Veterinary Journal 26:511-514, 1994. Pubmed reference: 7889930 .|
|1992||Chowdhary, B.P., Harbitz, I., Davies, W., Gustavsson, I. :|
|Localization of the calcium release channel gene in cattle and horse by in situ hybridization - Evidence of a conserved synteny with glucose phosphate isomerase. Animal Genetics 23:43-50, 1992. Pubmed reference: 1315127 .|
|1989||Klein, L., Ailes, N., Fackelman, G.E., Kellon, E., Rosenberg, H. :|
|Postanesthetic equine myopathy suggestive of malignant hyperthermia. A case report. Vet Surg 18:479-82, 1989. Pubmed reference: 2603379 . DOI: 10.1111/j.1532-950x.1990.tb01131.x.|
|1985||Riedesel, D.H., Hildebrand, S.V. :|
|Unusual response following use of succinylcholine in a horse anesthetized with halothane. J Am Vet Med Assoc 187:507-508, 1985. Pubmed reference: 4055481 .|
|1983||Hildebrand, S.V., Howitt, G.A. :|
|Succinylcholine infusion associated with hyperthermia in ponies anesthetized with halothane. Am J Vet Res 44:2280-4, 1983. Pubmed reference: 6660617 .|
|Manley, S.V., Kelly, A.B., Hodgson, D. :|
|Malignant hyperthermia-like reactions in three anesthetized horses. J Am Vet Med Assoc 183:85-9, 1983. Pubmed reference: 6874529 .|
|1981||Waldron-Mease, E., Klein, L.V., Rosenberg, H., Leitch, M. :|
|Malignant hyperthermia in a halothane-anesthetized horse. J Am Vet Med Assoc 179:896-8, 1981. Pubmed reference: 7341603 .|
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