Contents
Malignant Hyperthermia (MH)
Summary
Understanding the Results
Disease Name and Genes
Inheritance
Citations

Malignant Hyperthermia (MH)

Summary

Malignant Hyperthermia (MH) is an inherited disease that causes severe tying up and possible death in affected horses after exposure to anesthesia. It has been reported in Quarter Horses and related breeds, Thoroughbreds, Arabians, and ponies. Episodes may also be triggered by exercise, stress, or episodes of other myopathies such as PSSM1. Signs include high temperature and profuse sweating, rapid heart rate and breathing, muscle rigidity, and high blood pressure. Fatalities may be prevented by treatment with dantrolene prior to administering anesthesia or application of body-cooling therapy during episodes.

The most common known genetic cause of MH is an autosomal dominant variant of the RYR1 gene that encodes the ryanodine receptor (a calcium release channel) of the sarcoplasmic reticulum of skeletal muscle. The variant form of this channel leads to an uncontrolled release of intracellular calcium from the sarcoplasmic reticulum.

Less than 1% of Quarter Horses are affected, with most being of halter bloodlines. Horses affected with both the GYS1-R309H (PSSM1) and RYR1 (MH) mutation have higher exercise intolerance than those with PSSM1 alone. The American Quarter Horse Association requires genetic testing for MH and four other genetic conditions (GBED, PSSM1, HYPP, and HERDA).

Date of Last Update: 08/02/2016


Results

Understanding the Results

Results of the genetic test for MH are presented as shown below.

Malignant Hyperthermia (MH)
n/n Clear This horse tested negative for MH and does not carry the RYR1-R2454G mutation.
n/MH Affected Both the normal and mutant alleles are present. This horse is positive for the RYR1-R2454G mutation and is expected to display symptoms of MH.
MH/MH Affected This horse carries two copies of the RYR1-R2454G mutation and is positive for MH. The horse is expected to develop symptoms of MH.

Disease Name and Genes

Malignant Hyperthermia (MH) is caused by a missense mutation that replaces an Arginine (R) with a Glycine (G) at amino acid position 2454 in the RYR1 gene that encodes the ryanodine receptor (RYR1-R2454G).

Inheritance

Malignant Hyperthermia (MH) is associated with a dominant variant of the RYR1 gene (RYR1-R2454G). The dominant allele is commonly abbreviated as MH, with the recessive wild-type allele abbreviated as n.



A horse with one copy of the dominant allele (n/MH) will potentially have symptoms. If this horse is bred to a normal horse (n/n), each foal has a 50% chance of having one copy of the semidominant allele (n/MH) and a 50% chance of having two copies of the normal allele (n/n).



If two horses, each with one copy of the dominant allele (n/MH), are bred, each foal has a 25% chance of having two copies of the normal allele (n/n), a 50% chance of having one copy of the semidominant allele (n/MH), and a 25% chance of having two copies of the semidominant allele (MH/MH). Because horses with one copy (n/MH) or two copies (MH/MH) of the dominant allele are affected, each foal will have a 75% chance of being affected.



If a horse with two copies of the semidominant allele (MH/MH) is bred to a normal horse (n/n), all of the foals will have one copy of the semidominant allele (n/MH) and will be affected.

Citations

Aleman M et al. (2004). "Association of a mutation in the ryanodine receptor 1 gene with equine malignant hyperthermia." Muscle & Nerve. 30(3):356-365. PMID: 15318347.
Aleman, M et al. (2005). "Malignant Hyperthermia in a Horse Anesthetized with Halothane." Journal of Veterinary Internal Medicine. 19(3):363-367. PMID: 15954554.
McCue ME et al. (2009). "Polysaccharide storage myopathy phenotype in quarter horse-related breeds is modified by the presence of an RYR1 mutation." Neuromuscular Disorders. 19(1):37-43. PMID: 19056269.
Aleman, M et al. (2009). "Malignant hyperthermia associated with ryanodine receptor 1 (C7360G) mutation in Quarter Horses." Journal of Veterinary Internal Medicine. 23(2):329-334. PMID: 19220734.
Rosenberg, H et al. (2015). "Malignant hyperthermia: a review" Orphanet Journal of Rare Diseases. 10(0):93. PMCID: PMC4524368.

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