OMIA 000621-9796 : Malignant hyperthermia in Equus caballus

In other species: domestic cat , cattle , dog , pig , rabbit , deer , turkey

Possibly relevant human trait(s) and/or gene(s)s (MIM numbers): 145600 (trait) , 180901 (gene)

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.

Breeds: Appaloosa, Arabian, Quarter Horse, Thoroughbred.

Associated gene:

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

Variants

By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

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 American Quarter 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

References


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.
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.

Edit History


  • Created by Frank Nicholas on 10 Sep 2005
  • Changed by Frank Nicholas on 11 Sep 2011
  • Changed by Frank Nicholas on 09 Dec 2011
  • Changed by Frank Nicholas on 17 Oct 2012
  • Changed by Imke Tammen2 on 25 Apr 2022