A Genetic Concern: Immune-Mediated Myositis/MYH1 Myopathy

It took just days for the healthy weanling colt to go from well-fed and well-muscled to emaciated, despite ample feed and water.  

“If someone didn’t know the circumstances, they may have thought he was being starved because he had lost a drastic amount of weight across his top line and hindquarters,” said a horse owner, who prefers to remain anonymous. “I was so embarrassed. He went from muscled up to looking like I hadn’t fed him in months over just a couple days.  I had never seen anything like it.” 

Her weanling colt lost an incredible amount of muscle mass and weight literally overnight and she was frantic to figure out what was causing it. Her veterinarian had no idea what was going on.  

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Eventually, thanks to clues from her colt’s bloodwork and discovery that a sibling carried the gene for Immune Mediated Myositis (IMM), a quick genetic test confirmed the problem: Immune-Mediated Myositis, also referred to as Myosin-heavy chain myopathy (MYHM).  

IMM/MYHM is relatively new in the equine genetic disease world. The gene was identified in 2018, not long before the aforementioned colt got so sick. The owner had never heard of it. 

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Dr Carrie Finno, University of California-Davis, and Dr. Stephanie Valberg, Michigan State University, identified a mutation in the MYH1 gene that causes two forms of muscle disease in Quarter Horses and related breeds: Immune Mediated Myositis, which causes rapid atrophy of the topline and hindquarter muscles, and Non-Exertional Rhabdomyolysis, or tying up without exercise. This mutation in the Myosin Heavy Chain 1 (MYH1) gene causes an amino acid change detrimental to normal function of the myosin protein in muscle cells. The DNA mutation causes a change from a glutamic acid to glycine in the muscle protein. 

According to the U. C. Davis Veterinary Genetics Laboratory website (https://vgl.ucdavis.edu/test/imm) Myosin-heavy chain myopathy (MYHM) is considered a dominant genetic disease, meaning that a horse with only one copy of the gene can be affected. MYHM also has variable penetrance, meaning that not all horses with the mutation will develop the disease.  

The muscle atrophy attributed to IMM can result in the loss of 40 percent of muscle mass within 48-72 hours. Affected horses are usually under 8 years old, or are older than 17. Treatment with steroids can halt the muscle atrophy and may be combined with antibiotics if an infection is present. A diet of high quality protein and balanced vitamins and minerals during the recovery period can help in the recovery of muscle mass. Recurrence of muscle atrophy can occur and may require additional therapy. 

Emily Lloyd experienced this dramatic, rapid muscle loss with her filly. 

“The muscle just ‘melts’ off of their topline and rump VERY quickly,” she said. “It all happens fast. My filly stayed bright eyed, was not lethargic at all and never lost her appetite, but lethargy and appetite loss (along with stiffness and weakness) are common for other horses during an episode.” Just like IMM is linked with the MYH1 gene, non-exertional rhabdomyolysis (tying up not caused by exercise) is also a clinical presentation of the MYH1 gene, but that type of muscle tightness isn’t part of an IMM episode. 

While some horses show symptoms such as swollen lymph nodes, Emily said that the rapid muscle loss has been her only indicator that her IMM/IMM carrier filly is starting to have an episode.  

“I keep Dexamethasone on hand so I can treat immediately as soon as I see the slightest muscle loss on her topline in hopes of stopping the loss before it gets severe,” she said. 

Non-exertional rhabdomyolysis causes severe muscle pain, stiffness and reluctance to move. Horses lying down may have difficulty rising due to their high pain levels. Horses with MYHM can develop this form of muscle damage without showing any muscle atrophy. Treatment with steroids can decrease muscle damage and horses with non-exertional rhabdomyolysis can recover but they are susceptible to more episodes and to IMM. 

Environmental factors can also play a role in whether or not a horse carrying MYHM will develop IMM or non-exertional rhabdomyolysis. About 39 percent of MYHM horses have a history of exposure to a triggering factor such as Strangles infection or exposure, respiratory virus infection, Pigeon fever, or vaccination with Influenza, Equine Herpes Virus 4 or Strangles vaccine, according to the published study by Drs. Valberg and Finno. 

The unnamed horse owner said she had not vaccinated her colt prior to his IMM episode, but that she had noticed that one lymph node under his jaw was slightly swollen and that he seemed to be trying to catch a cold for about two weeks before his condition drastically deteriorated.  

“Testing showed that he is homozygous, carrying two copies of the gene (My/My),” she said. “I have now tested my other horses, and it turns out that several other horses I own each have one copy. They have not had any issues though. After we figured out what was going on with him and started steroid treatment he started to improve. I was able to get the weight back on and stiffness in his back legs slowly went away, but it took at least two months until he wasn’t stiff anymore.” 

The American Quarter Horse Association currently requires breeding stallions to be tested for five genetic diseases before their foals can be registered. MYHM testing is not currently required by the AQHA. Kylie Mull, AQHA genetic disease specialist, said that there is a lot of awareness and interest in IMM/MYHM testing.  

“Since we are a member organization, a motion to add IMM/MYHM testing to the list of required genetic disease tests will have to be brought to the convention and voted on by our members,” she said.  

The 2020 AQHA convention was cancelled due to Covid-19, but it is likely that MYHM testing will be brought up at the 2021 convention. 

Genetic testing for IMM/MYHM is available from several laboratories including the Veterinary Genetics Laboratory at U. C. Davis and can be a tool for breeders to consider.  

UC Davis Veterinary Genetics Laboratory director Dr. Rebeca Bellone says that results from testing for MYHM are assisting in clinical management of both affected horses and those at risk.  

The horse owner mentioned earlier said that she does not fault her colt’s breeder at all but wants to help other horse owners become aware of the effects of IMM/MYHM.   

“He has had no further issues since he got sick,” she said. “I have vaccinated him nasally, which is supposed to be easier.  I have vaccinated my other three horses that are only single copy of MYHM as usual. They have had no reaction from normal vaccinations. I would love to learn more about IMM/MYHM myself and am willing to help others in any way I can.”