English
Myosin Heavy Chain Myopathy (MYHM) is a muscle disease that can affect Quarter Horses and related breeds with the associated mutation in the MYH1 gene.
MYH1, also called myosin heavy chain 1, is a gene that encodes a type of myosin found in fast-twitch muscle. Myosin is a protein responsible for muscle contraction and other motor functions. [1][2]
Horses with the MYH1 mutation have myosin with an altered amino acid sequence which interferes with the function of myosin in muscle tissue.
Horses with the MYH1 gene mutation are susceptible to MYHM, although not all will develop the condition. MYHM presents in two forms, including immune-mediated myositis (IMM) and non-exertional rhabdomyolysis.
Treatment of MYHM in both of its forms may include the administration of corticosteroids and antibiotics. Horses with IMM and non-exertional rhabdomyolysis may or may not recover fully, and recurrence of either condition is possible.
The best way to prevent MYHM is by using genetic testing to determine which horses have the MYH1 gene to make informed breeding decisions.
What is MYHM in Horses?
Myosin-heavy chain myopathy (MYHM) is a muscle disease that can affect horses with a genetic mutation in the MYH1 gene. [1][2]
Breeds, including Quarter horses and related breeds, such as American Paint, Appaloosa, and crosses, are most often affected by MYHM. [1][2][3]
The MYH1 gene contains the genetic information required for the body to produce a muscle specific protein called myosin heavy chain 2X. This protein is present in fast-contracting muscle fibers referred to as type 2 muscle fibers. [1]
More than 50% of the locomotor muscles in Quarter horses consist of type 2 muscle fibers. [3]
Types of MYHM
MYHM results in two distinct clinical disease presentations: immune mediated myositis (IMM) and non-exertional rhabdomyolysis.
IMM is believed to be initiated by a trigger such as vaccination or infectious illness and results in rapid muscle atrophy. Non-exertional rhabdomyolysis results in stiff, swollen, and painful muscles.
Horses with IMM and non-exertional rhabdomyolysis have increased serum creatine kinase (CK) activity on laboratory tests. IMM affected horses also have white blood cell (lymphocytes) infiltration of their gluteal or epaxial muscles on biopsy samples.
Immune-Mediated Myositis
IMM describes episodes of severe muscle atrophy in horses with the MYH1 genetic mutation. [4] IMM involves an immune system attack (autoimmune response) on the muscle tissues.
Specific triggers activate the immune system of horses with an altered MYH1 gene, resulting in inflammation and damage to type 2 muscle fibers and surrounding blood vessels. [4]
In horses affected by IMM, muscle loss (atrophy) occurs in the back and rump. The condition results in a rapid loss in the size and strength of these muscles. [4]
IMM can result in a 40% loss of muscle mass within 48 hours. [4] Muscle wasting caused by the condition can persist for months.
Non-Exertional Rhabdomyolysis
A second form of MYHM caused by a genetic mutation in the MYH1 gene is known as non-exertional rhabdomyolysis or “tying-up”. [4]
This form of the condition involves severe pain, stiffness, and muscle swelling in some cases. Non-exertional rhabdomyolysis can cause muscle damage that is not associated with exercise.
Unlike IMM, muscle atrophy is not typically present in horses with non-exertional rhabdomyolysis. [4]
Differentiation
The main features that differentiate non-exertional rhabdomyolysis from IMM are:
- No rapid‐onset muscle atrophy in horses with non-exertional rhabdomyolysis. [1]
- The absence of a type of white blood cells (lymphocytes) infiltrating the gluteal or epaxial muscles on biopsy samples from horses with non-exertional rhabdomyolysis. [1][4][5]
Chronic muscle atrophy in horses can result from causes other than MYHM. Examples include malnutrition, underlying illnesses such as cancer and kidney disease (cachexia), equine motor neuron disease, muscle disease (myopathy) due to vitamin E deficiency, pituitary pars intermedia dysfunction (PPID) and old age. [4]
Prevalence
MYH1 Genetic Mutation
The MYH1 genetic mutation occurs in approximately 7% of Quarter horses. [3]
Due to breeding for select disciplines, the MYH1 genetic mutation occurs in 16-22% of horses used for reining, halter-showing, and working cows. [2][3]
IMM
It is unknown what percentage of horses with the MYH1 mutation will develop IMM. IMM rarely occurs in horses that are not Quarter horses or a related breed.
Horses younger than eight and older than 17 are at an increased risk for IMM. [6] Both males and females are affected.
Non-exertional Rhabdomyolysis
Quarter horses and related breeds with the MYH1 genetic mutation are susceptible to developing non-exertional rhabdomyolysis. [3]
It is unknown what percentage of horses with the MYH1 mutation will develop non-exertional rhabdomyolysis.
How the MYH1 Gene Mutation is Inherited
Genes are the primary unit of heredity. They are segments of DNA that determine a specific trait.
Genes have different forms or variations called alleles, which are sets of matching genes, one received from each parent.
Alleles
The MYH1 gene can exist with alleles named: [3]
- N = Normal/Unaffected
- My = Myosin-heavy chain myopathy
Genotypes
Horses with an N/N genotype have no copies of the MYHM mutation and do not have an increased risk for IMM or non-exertional rhabdomyolysis.
Horses with an N/My genotype may develop MYHM. [3] This is a heterozygous mutation, as one allele is mutated. These horses will pass the MYH1 gene mutation to 50% of their offspring. [8]
Horses with the My/My genotype may be more severely affected by MYHM, have more rapid muscle atrophy and experience reoccurrence of the condition. [3][4][7]
The My/My genotype is called a homozygous mutation, as both alleles are mutated. Horses with the MY/MY genotype will pass the MYH1 gene mutation to all their offspring. [8]
However, not all horses with the MYH1 gene mutation will develop MYHM.
Causes of MYHM
Causes of IMM
IMM is an immune mediated disease involving abnormal activity of the immune system. The immune system of horses with IMM reacts to myosin proteins normally present in the muscle cells.
Muscle atrophy occurs in IMM-affected horses when the immune system responds to molecules present on the cells of muscle tissue called antigens. The immune system perceives these antigens as foreign and launches an attack.
When triggered, the MYH1 mutation causes the immune system to signal white blood cells to infiltrate muscle tissue and destroy type 2 muscle fibers. [6][7]
Potential triggers that cause the immune system to attack type 2 muscle fibers include: [3]
- Infectious agents such as Streptococcus equi and respiratory viruses
- Immune stimulants
- Vaccines (influenza or others)
Other triggers likely exist, although these have yet to be identified.
Causes of Non-Exertional Rhabdomyolysis
Rhabdomyolysis involves damage to and the death of muscle cells. This condition can occur due to exertion and when exertion is not a factor (as in non-exertional rhabdomyolysis).
Rhabdomyolysis is characterized by the breakdown of muscle cells and the release of their cellular components into the bloodstream.
It is unclear exactly how the MYH1 mutation contributes to non-exertional rhabdomyolysis. Potential explanations may involve: [3]
- An immune-response similar to IMM
- Altered motor protein function: The mutation may change how motor proteins, including myosin, interact during muscle contractions
- Infections caused by bacteria such as Streptococcus equi and Anaplasma phagocytophila
- Fungal infections affecting the guttural pouch are also associated with non-exertional rhabdomyolysis