Understanding Myosin-Heavy Chain Myopathy in Quarter Horses

Myosin-heavy chain myopathy (MYHM) is a muscle disease that leads to two distinct clinical presentations: immune-mediated myositis and non-exertional rhabdomyolysis. The specific genetic mutation linked to the risk of MYHM is found in the MYH1 gene, first identified in horses with immune-mediated myositis (IMM), which is why the DNA test was originally termed IMM. However, after recognizing that two distinct clinical forms arise from the same genetic mutation, the DNA test was renamed Myosin-heavy chain myopathy (MYHM) for better representation of both clinical syndromes.

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

In the IMM form of myosin-heavy chain myopathy, affected Quarter Horses initially exhibit stiffness, weakness, and a reduced appetite, leading to a rapid loss of about 40% of muscle mass within 72 hours. Inflammatory cells, particularly lymphocytes, are found in muscle fibers and around blood vessels, mainly affecting the gluteal (hindquarter) and back muscles. In the non-exertional rhabdomyolysis form of myosin-heavy chain myopathy, these horses display stiffness, a short stride, firm muscles, and may quickly lie down without being able to rise. Such horses can have dark coffee-colored urine, and blood tests show significantly elevated muscle enzyme levels. Notably, there is often no evidence of lymphocytes present in the muscles of horses with non-exertional rhabdomyolysis.

The Veterinary Genetics Laboratory (VGL) tests for susceptibility to myosin-heavy chain myopathy and reports the genetic mutation as My. The inheritance pattern for this disorder is autosomal codominant with variable penetrance, meaning that both horses with one or two copies of the My variant are at risk for disease; however, not all horses carrying the My mutation will exhibit clinical signs. My is considered a genetic risk factor which necessitates certain environmental 'triggers' (e.g., infection, vaccination) to manifest as clinical disease. Additionally, homozygous horses (My/My) that do display clinical signs tend to be more severely affected. Age also influences disease susceptibility, with younger and older Quarter Horses being more likely to develop symptoms due to environmental triggers typically around the ages of 8 years and younger or 17 years and older.

The frequency of the My variant among the general Quarter Horse population was initially estimated at around 4%, with approximately 7.5% of Quarter Horses having one copy of the My allele. This frequency increases in certain subsets, including reining (13.5%), working cow (8.5%), and halter (8%) horses, while it is not observed in the barrel racing and racing categories. In a 2022 retrospective study led by Dr. Stephanie Valberg, Mary Anne McPhail Dressage Chair in Equine Sports Medicine at Michigan State University, along with Dr. Carrie Finno, Gregory L. Ferraro Endowed Director of the UC Davis Center for Equine Health, in collaboration with Dr. Rebecca Bellone and Shayne Hughes of VGL, a higher prevalence was found for the MYH1 mutation, reaching 29% in the study population. Homozygous horses constituted a small fraction (~3%), with 80% of these horses experiencing muscle atrophy that was unlikely to resolve, compared to only 20% of heterozygous horses. Notably, the study indicated that vaccination or infectious diseases were not observed in 75% of homozygous and 54% of heterozygous horses that developed atrophy or stiffness, suggesting further investigation is needed to identify other environmental triggers.

Previous studies have shown that approximately 40% of horses that exhibit muscle atrophy symptoms related to MYHM have had prior exposure to Streptococcus equi subsp. equi infection, respiratory viruses, or certain vaccinations. Both male and female Quarter Horses are affected in equal measure.

While not all triggers for MYHM are currently known, confirmed triggers include:

- Respiratory infections

- Streptococcal infections, particularly strangles

- Corynebacterium pseudotuberculosis infections (also known as "pigeon fever")

- Vaccinations that may cause muscle damage, particularly for influenza, rhinovirus, and strangles

- Immune stimulants

- Muscle damage

Recommendations for horses genotyped as N/My or My/My include:

- Avoid all strangles vaccines

- Prefer intranasal vaccines when possible and limit necessary intramuscular vaccines to those essential for horses in specific regions

- Space out vaccinations over time

Horse breeders can benefit from the MYHM test to inform breeding strategies that minimize the risk of producing at-risk horses. Additionally, MYHM testing can aid in clinical decisions regarding potential environmental triggers and better guide vaccination protocols for heterozygous (N/My) and homozygous horses (My/My), reducing the risk of an autoimmune response. Test results may also assist clinicians in confirming diagnoses of IMM or non-exertional rhabdomyolysis when linked to the My allele. Furthermore, testing for MYHM may facilitate additional research endeavors aimed at unraveling other risk factors, paving the way for better management strategies.

Testing for MYHM is highly recommended for Quarter Horses, Quarter Horse crosses, and other breeds influenced by Quarter Horse genetics.