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.
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Diagram of how Myosin-heavy chain myopathy (MYHM) results in two distinct clinical disease presentationsClick here for Price and Turnaround Time

Phenotype: 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.

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Turnaround Time
At least 15 business days; may be delayed beyond 15 business days if sample requires additional testing, or a new sample is requested.
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.

    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 was initially estimated at about 4%, with approximately 7.5% of Quarter Horses having 1 copy of the My allele; the frequency being higher in the reining (13.5%), working cow (8.5%) and halter (8%) categories, and not observed in barrel and racing categories. In 2022, results from a retrospective study conducted with VGL clients revealed a higher prevalence of the MYH1 mutation in the study population. The study led by Dr. Stephanie Valberg, Mary Anne McPhail Dressage Chair in Equine Sports Medicine from Michigan State University, and Dr. Carrie Finno, Gregory L. Ferraro Endowed Director of the UC Davis Center for Equine Health (CEH), in collaboration with Dr. Rebecca Bellone and Shayne Hughes of the UC Davis Veterinary Genetics Laboratory (VGL), found the prevalence of the MYH1 mutation to be 29% in the study population, with homozygous horses being relatively rare in the population (~3% of the study population were My/My). Muscle atrophy that was less likely to resolve occurred in 80% of homozygous horses whereas only about 20% of the heterozygous horses experienced rapid muscle atrophy. Importantly, the study also showed that factors like vaccination or infectious diseases were not apparent in 75% of homozygous horses and 54% of heterozygous horses known to have developed atrophy or stiffness, indicating more work is needed to better understand additional environmental triggers.

    Previous studies had indicated that 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

    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.

    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

    Valberg, SJ, Schultz, AE, Finno, CJ, Bellone, RR, Hughes, SS. (2022) Prevalence of clinical signs and factors impacting expression of myosin heavy chain myopathy in Quarter Horse-related breeds with the MYH1E321G mutation. J Vet Intern Med, 1- 8. doi:10.1111/jvim.16417

    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