Myofibrillar myopathy (MFM) is a newly identified muscle disorder that causes exercise intolerance in horses.

MFM is a genetic condition that results from the abnormal build-up of desmin in muscle tissue. Desmin is a protein that is important for muscle contraction.

In response to strenuous exercise, horses with MFM may experience pain, stiffness, lameness, poor stamina and intermittent gait abnormalities. [5]

This disorder has been identified mostly in Warmblood, Arabian horses and their crosses. Affected Warmbloods often refuse to collect under saddle while Arabians tend to have episodes of tying-up or extreme cramping. [7]

There is no cure for Myofibrillar Myopathy in horses, but tolerance to exercise can be improved with management strategies to address diet and conditioning. However, some horses may be retired from competition due to poor performance.

Myofibrillar Myopathy

Myofibrillar myopathy is an exertional muscle disorder that shares clinical signs with more common exercise disorders, such as polysaccharide storage myopathy type 1 or type 2 (PSSM1 or PSSM2) or recurrent exertional rhabdomyolysis (RER).

Unlike RER, horses with MFM do not have elevations in serum creatine kinase (CK) or aspartate transaminase (AST). [6]

MFM can present differently in individual cases, making diagnosing difficult without a muscle biopsy.

Signs of MFM in Horses

Muscle disorders can dramatically impair the abilities of horses in various levels of work by causing pain and weakness in response to exercise. [6]

Clinical signs of MFM in horses can present during and after an exercise bout, resembling other muscle disorders such as PSSM or tying up. [6]

The signs of MFM include: [7][8][9]

  • Poor performance
  • Muscle pain & stiffness
  • Tying-up or rhabdomyolysis
  • Reluctance to move forward
  • Vague hindlimb lameness
  • Tremors
  • Extreme sweating
  • Movement abnormalities
  • Pigmenturia or dark urine

It has been suggested that the clinical presentation of MFM can differ between breeds. [7] For example, Arabians are more likely to experience tying up than Warmbloods. The actual cause of these differences is unknown but may be related to breed genetics.

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Cause of MFM

The genetic cause of MFM remains under investigation and likely involves a complex interaction between several genes, instead of one specific gene. [9][12]

MFM-affected horses have a disorderly alignment of broken myofibrils (contractile proteins) in their muscle cells. These damaged myofibrils cause a clumpy build-up of the cytoskeleton protein desmin near the breakage sites in fast-twitch muscles. [6][7]

The alignment of muscle proteins is essential for strength and effective muscle contractions. [6] When desmin cannot stabilize muscle filaments and maintain alignment, muscle contraction becomes less effective. This leads to exercise intolerance and early exhaustion.

MFM in Arabians

The Arabian is a successful endurance breed because of metabolic adaptations that allow the horse to efficiently break down fatty acids, providing energy for long-distance exercise.

However, this adaptation can also lead to oxidative stress during aerobic exercise, in which antioxidant defences in the body are overwhelmed. [1][7] This imbalance can affect several physiological processes, including muscle function.

Arabians with MFM seem to have a deficiency of cysteine antioxidants in the body, which are responsible for combatting inflammation and oxidative stress. [10]

This can lead to chronic protein loss and build-up of excessive desmin during or following exercise.

MFM in Warmbloods

The onset of exercise intolerance in MFM-affected warmblood horses usually occurs between 6-8 years of age. [6] Even high-performing horses can lose stamina and the ability to collect in several gaits.

Many warmbloods lose the ability to sustain a normal canter for more than a few strides along with sloppy and stiff canter transitions. They may demonstrate hindlimb lameness with no apparent cause.

Exercise intolerance in warmbloods with MFM may be explained by abnormal adjustment of muscle fibre signalling pathways to exercise demands. Protein synthesis may be reduced resulting in ineffective muscle repair, damage to cell mitochondria and increased oxidative stress. Warmbloods with MFM may also show slow-onset muscle atrophy. [7]

Other breeds

In rare cases, MFM has been identified in Thoroughbreds, Quarter Horses and Paso Finos through muscle biopsy. [7] However, little is known about the causes, symptoms, management or prognosis of MFM in these breeds.

Diagnosis

A detailed examination including biopsy and immunohistochemical staining is required for diagnosis.

There are commercially available genetic tests for MFM that report the presense of the variants (P2, P3, P4). However, when comparing control horses to those with features of MFM based on muscle biopsy analysis, the presense of these variances does not differ. [11] Therefore, the current genetic tests should be considered inaccurate for an MFM diagnosis.

Because MFM is relatively rare, your veterinarian will first examine your horse to rule out other conditions and causes of exercise intolerance.

Physical Examination

A physical examination must be conducted to rule out lameness and neurological conditions that could be causing MFM symptoms.

If a horse shows alterations in their gait or symptoms of hoof pain, your veterinarian will ask about your horse’s medical history and conduct a hands-on assessment to examine and palpate muscles, joints and tendons.

A horse with MFM may have lameness in the hindlimb without apparent cause, so isolating the specific location of pain through physical examination is often difficult. [7]

Muscle Biopsy

MFM can be diagnosed with a muscle biopsy in which tissue is removed from affected muscles to be analyzed microscopically. These biopsies are sensitive and can yield false negative or positive results. [7] Therefore, other conditions must be ruled out first.

Muscle tissue can be removed for sampling safely, quickly and painlessly through a percutaneous needle biopsy. [3] The gluteus medius muscle or semimembranosus tendinosis muscle are commonly sampled for diagnosis.

The muscle fibres are examined to determine if Type 2A or 2B (fast-twitch) muscle fibres contain desmin build-up. [6][8]

If the desmin aggregates are found in mature muscle cells, the horse can be diagnosed with MFM. [6] However, a false positive diagnosis may occur if the sample is taken from a horse with actively regenerating muscle fibres.

If a biopsy is needed for diagnosis, it should be conducted following the physical examination and before other treatment plans are commenced. Treatment can decrease the build-up of desmin, potentially leading to a false negative result for MFM. [6]

Immunohistochemical Stains

Immunohistochemical staining for desmin is currently the most accurate way to diagnose myofibrillar myopathy. Immunohistochemistry uses antibodies to detect the presence of specific protein markers in biological tissue.

Stains can identify desmin aggregates in tissue samples obtained during a muscle biopsy. Desmin build-up is identified by abnormal red clumping in scattered muscle fibres. [8]

This method of diagnosis is not reliable for horses under eight years of age, horses that are out of work or horses under specific management plans for MFM. Desmin build-up is difficult to identify in young horses, as significant accumulation is needed for diagnosis. [6]

Given the limitations of current diagnostic techniques, more sensitive markers to identify MFM are needed.

Differential Diagnosis

It is recommended that horses undergo neurological and lameness examinations before considering an MFM diagnosis. Other conditions tha