Discovered at UC Davis Myosin-Heavy Chain Myopathy (MYHM)

Quick Summary

Myosin-heavy chain myopathy (MYHM) is a muscle disease in Quarter Horses and related breeds that results in two distinct clinical disease presentations, immune-mediated myositis (IMM) and non-exertional rhabdomyolysis. Both presentations involve muscle loss or damage and are linked to the same genetic variant.
Search Keywords
immune
immune-mediated
myositis
autoimmune
IMM
muscle

Diagram of how Myosin-heavy chain myopathy (MYHM) results in two distinct clinical disease presentationsPhenotype: Myosin-heavy chain myopathy (MYHM) is a muscle disease in Quarter Horses and related breeds that results in two distinct clinical disease presentations. The first presentation is called immune-mediated myositis or IMM and it is characterized by episodes of severe muscle atrophy following an autoimmune event. The second is severe muscle pain and damage termed non-exertional rhabdomyolysis or “tying-up” that is not associated with exercise and may or may not have muscle atrophy.

Mode of Inheritance: Autosomal codominant with variable penetrance

Alleles: N = Normal/Unaffected, My = Myosin-heavy chain myopathy

Breeds appropriate for testing: Quarter Horse and related breeds

Explanation of Results:

  • Horses with N/N genotype will not have increased susceptibility for a myosin-heavy chain myopathy and cannot transmit the MYHM variant to their offspring.
  • Horses with N/My genotype may develop a myosin-heavy chain myopathy. They may transmit this MYHM variant to 50% of their offspring. Matings to horses with the N/N genotype will result in a 50% chance of producing a foal that may develop myosin-heavy chain myopathy.
  • Horses with My/My genotype may develop a more severe form of a myosin-heavy chain myopathy. They will transmit this MYHM variant to all of their offspring.
Price

$40 one test per animal

Panels Available
Additional Details

Myosin-heavy chain myopathy (MYHM) is a muscle disease that results in two distinct clinical disease presentations, immune-mediated myositis and non-exertional rhabdomyolysis. The specific genetic mutation associated with risk for MYHM is in the MYH1 gene and was first identified in horses with immune-mediated myositis or IMM and is why initially the DNA test was named IMM. However, upon determining that there are two distinct clinical forms associated with the same mutation, the name of the DNA test was changed to Myosin-heavy chain myopathy (MYHM) to better reflect the two clinical syndromes.

The genetic variant associated with myosin-heavy chain myopathy was identified by Drs. Finno (UC Davis) and Valberg (Michigan State University) in 2017. This missense mutation is in the Myosin Heavy Chain 1 (MYH1) gene (chr11:52,993,878T>C) and causes an amino acid change from a glutamic acid (E) to glycine (G) at position 321 of the protein, which affects protein function.

With the IMM form of myosin-heavy chain myopathy, horses initially experience stiffness, weakness, and a decreased appetite followed by the rapid loss of 40% of muscle mass within 72 hours. Inflammatory cells, particularly lymphocytes, are present in muscle fibers and surrounding blood vessels, with preferential targeting of the gluteal (hindquarter) and back muscles. With the non-exertional rhabdomyolysis form of myosin-heavy chain myopathy, horses initially show stiffness, a short stride, firm muscles and may quickly lie down and be unable to get back up. These horses can have dark coffee-colored urine and blood samples show very high levels of muscle enzymes. There is often no evidence of lymphocytes in the muscle of horses with non-exertional rhabdomyolysis.

About 40% of horses that develop signs of muscle atrophy with MYHM have a history of exposure to Streptococcus equi subsp. equi infection, respiratory virus, or vaccination with influenza, equine herpes virus 4, or Streptococcus equi subsp. equi. Males and females are equally affected.

All of the triggers for MYHM are not yet known but those that are known include;

  • Respiratory infections
    • Streptococcal infection and strangles, in particular
  • Corynebacterium pseudotuberculosis infections (aka “pigeon fever”)
  • Vaccinations that cause muscle damage
    • Often influenza, rhinovirus, and strangles vaccines
  • Immune stimulants
  • Muscle damage

Recommendations for horses who genotype N/My or My/My are:

  1. Avoid any form of strangles vaccines
  2. Use intranasal vaccines where possible and only use intramuscular vaccines that are necessary for horses in that region of the country
  3. Spacing vaccines out over time is also recommended

The VGL tests for susceptibility to myosin-heavy chain myopathy and reports the variant as My. The mode of inheritance for this disorder is autosomal codominant with variable penetrance. This means that horses with one or two copies of My are susceptible to disease, but not all horses with My will develop signs of disease. My is considered an associated genetic risk factor and requires specific environmental “triggers” of the immune system (e.g. infection, vaccination) to manifest as clinical disease. It has also been noted that My/My (i.e. homozygous) horses that show clinical signs are more severely affected. Age has also been shown to contribute to disease risk, with younger and older horses more likely to develop disease due to environmental triggers. Affected horses are typically 8 years and younger or 17 years and older.

The frequency of the My variant in the general Quarter Horse population is estimated at about 4%, with approximately 7.5% of Quarter Horses having 1 copy of the My allele. The frequency is higher in the reining (13.5%), working cow (8.5%) and halter (8%) categories, and not observed in barrel and racing categories.

Horse breeders can utilize the MYHM test to design appropriate breeding strategies that avoid producing at-risk horses. Testing for MYHM can also assist in clinical decisions about potential exposure to environmental triggers and help guide vaccination protocols for heterozygous (N/My) and homozygous horses (My/My), thereby lowering the chance of an autoimmune event. Testing results can also help clinicians confirm diagnosis of IMM or non-exertional rhabdomyolysis cases suspected to be caused by the My allele. Further, testing for MYHM has the potential to assist in additional research that should help to elucidate the other risk factors, allowing for the potential to develop more precise management strategies.

Testing is recommended for Quarter Horses, Quarter Horse crosses, and related breeds with Quarter Horse influence.

Turnaround Time
2-6 business days
Type of Sample

Species

Type of Test

Results Reported As
Test Result Immune-Mediated Myositis (IMM/MYH1)
N/N No copies of the MYHM mutation. Horse does not have increased susceptibility for IMM or non-exertional rhabdomyolysis.
N/My 1 copy of the MYHM mutation is present. Horse may develop IMM following infection or vaccination, or non-exertional rhabdomyolysis. Horse can pass on the mutation to 50% of offspring.
My/My 2 copies of the MYHM mutation are present. Horse is at risk and may develop IMM following infection or vaccination, or non-exertional rhabdomyolysis. Horses will pass on the mutation to all offspring.
References

Lewis, S. S., Valberg, S. J., & Nielsen, I. L. (2007). Suspected immune-mediated myositis in horses. Journal of Veterinary Internal Medicine, 21(3), 495-503. doi: 10.1111/j.1939-1676.2007.tb02996.x

Durward-Akhurst, S. A., & Valberg, S. J. (2018). Immune-Mediated Muscle Diseases of the Horse. Veterinary Pathology, 55(1), 68-75. doi: 10.1177/0300985816688755

Finno, C. J., Gianino, G., Perumbakkam, S., Williams, Z. J., Bordbari, M. H., Gardner, K. L., Burns, E., Peng, S., Durward-Akhurst, S. A., & Valberg, S. J. (2018). A missense mutation in MYH1 is associated with susceptibility to Immune-mediated myositis in Quarter Horses. Skeletal Muscle, 8(1). doi: 10.1186/s13395-018-0155-0

Valberg, S.J., Henry, M.L., Perumbakkam, S., Gardner, K.L., & Finno, C.J. (2018). An E321G MYH1 mutation is strongly associated with nonexertional rhabdomyolysis in Quarter Horses. Journal of Veterinary Internal Medicine, 32(5), 1718-1725. doi: 10.1111/jvim.15299

Gianino, G.M., Valberg, S.J., Perumbakkam, S., Henry, M.L., Gardner, K., Penedo, C., & Finno, C.J. (2019). Prevalence of the E321G MYH1 variant for immune-mediated myositis and nonexertional rhabdomyolysis in performance subgroups of American Quarter Horses. Journal of Veterinary Internal Medicine, 33(2), 897-901. doi: 10.1111/jvim.15393