Contents
Myofibrillar Myopathy (MFM)
Summary
Understanding the Results
Disease Name and Genes
Inheritance
Citations

Myofibrillar Myopathy (MFM)

Summary

Myofibrillar Myopathy (MFM) is a form of exercise intolerance. The clinical signs manifesting during or after exercise resemble other types of exertional rhabdomyolysis. During an episode, horses are reluctant to move, experience pain, stiffness, and tremors, and sweat profusely. Serum creatine kinase (CK) and aspartate aminotransferase (AST) are elevated, indicating muscle damage. In severe episodes, pigmenturia (coffee-colored urine due to the presence of myoglobin), inability to stand, and death can occur. These symptoms resemble other forms of exercise intolerance such as Polysaccharide Storage Myopathy (PSSM), Recurrent Exertional Rhabdomyolysis (RER), and Vacuolar Myopathy (VM).

Myofibrillar Myopathy (MFM) is distinct from these other forms of exercise intolerance with respect to findings on muscle biopsy. Histopathology shows ectopic accumulation of cytoskeletal proteins (e.g. desmin) and Z-disc degeneration. Focal myofibrillar disruption with accumulation of glycogen particles is seen. The condition has been observed in a subset of Arabian horses with exercise intolerance. Initial descriptions of MFM classified it as a subtype of Recurrent Exertional Rhabdomyolysis (RER) because it was a form of exercise intolerance observed in Arabians and Thoroughbreds. Researchers at EquiSeq currently think that it more closely resembles Polysaccharide Storage Myopathy, type 2 (PSSM2).

Researchers at EquiSeq have identified a semidominant allele of an undisclosed gene that causes MFM in Thoroughbreds and related breeds. The results are not yet published in a peer-reviewed academic journal. Prior to publication, the variant has been termed P3.

Horses that carry one copy of the variant (n/P3) have a predisposition to develop MFM (also diagnosed as PSSM2). We have not yet identified horses with two copies of the variant (P3/P3). Dietary therapy (a high protein diet) and a specific exercise regimen may help to manage the symptoms.

Date of Last Update: 08/07/2016


Results

Understanding the Results

Results of the genetic test for MFM are presented as shown below.

Myofibrillar Myopathy
n/n Clear This horse tested negative for P3, the MFM-predisposing variant identified in Thoroughbreds. The horse will not pass on the defect to its offspring.
n/P3 Affected Both the normal and mutant alleles are present. This horse is positive for the P3 variant and may develop symptoms of exercise intolerance.
P3/P3 Affected This horse carries two copies of the P3 variant. The horse is expected to develop symptoms of exercise intolerance.

Horses carrying the P3 variant develop symptoms of exercise intolerance as they age. The age of onset and the severity of symptoms is variable.

Disease Name and Genes

The term Myofibrillar Myopathy (MFM) has been applied to the condition seen in some Arabians and Thoroughbreds with exercise intolerance. This condition has also been previously described as a type of Polysaccharide Storage Myopathy, type 2 (PSSM2).

MFM is associated with a semidominant allele (P3) of an undisclosed gene.

Inheritance

MFM is associated with a semidominant allele of an undisclosed gene that likely has incomplete penetrance. The semidominant allele is commonly abbreviated as P3, with the recessive wild-type allele abbreviated as n.



A horse with one copy of the semidominant allele (n/P3) will potentially have symptoms. If this horse is bred to a normal horse (n/n), each foal has a 50% chance of having one copy of the semidominant allele (n/P3) and a 50% chance of having two copies of the normal allele (n/n).



If two horses, each with one copy of the semidominant allele (n/P3), are bred, each foal has a 25% chance of having two copies of the normal allele (n/n), a 50% chance of having one copy of the semidominant allele (n/P3), and a 25% chance of having two copies of the semidominant allele (P3/P3). Because horses with one copy (n/P3) or two copies (P3/P3) of the semidominant allele are affected, each foal will have a 75% chance of potentially being affected.



If a horse with two copies of the semidominant allele (P3/P3) is bred to a normal horse (n/n), all of the foals will have one copy of the semidominant allele (n/P3) and will potentially be affected.

Citations

Valberg SJ et al. (2016). "Suspected myofibrillar myopathy in Arabian horses with a history of exertional rhabdomyolysis." Equine Vet J.. 48(5):548-556. PMID: 26234161.

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