BEVA warns against unvalidated genetic tests

BEVA has offered strong advice to horse owners to steer clear of using independent and unvalidated genetic testing for certain myopathies.

The association is concerned about a growing trend for use of tests among some breed groups for myopathies including type 2 polysaccharide storage myopathy (PSSM2), myofibrillar myopathy (MFM) or muscle integrity myopathy (MIM).

But evidence to support use of the tests is lacking, says BEVA, while drastic results in some cases have included euthanasia of seemingly normal animals.

Temptation

Vet Richard Piercy, of the comparative neuromuscular diseases laboratory, RVC, said: “There is currently no scientifically validated genetic test for PSSM2, MFM or MIM.

“Scientists still do not know whether these are diseases at all, or whether they reflect histopathological features of non-specific muscle damage that might have various genetic, but also environmental, causes.

“It can, of course, be very tempting for a horse owner, when their horse has signs that might suggest a muscle problem, to seek any answer they can find, particularly when the problem is proving challenging to diagnose and manage.”

‘Unsubstantiated result’

Prof Piercy added: “It might be even more tempting for an owner to believe an unsubstantiated genetic result when it ‘fits’ with what they have suspected.

“But given the high prevalence of the genetic variants in the horse population that are tested for, many horses will test positive just by chance – whether or not they have any disease at all.”

Although type 1 PSSM can be diagnosed by DNA testing of a mutation that has been robustly evaluated^1,2, clinical evaluation, biochemical testing and, in some cases, muscle biopsy are described by BEVA as the optimal ways to identify horses with myopathies.

Unknown causes

As it is not yet known what causes PSSM2, MFM or MIM or whether they are specific diseases at all, recommendations for treatments, management or prognosis are speculative at best, says BEVA.

While companies in Europe and the US offer a panel of genetic tests commercially for diagnosis of equine muscle diseases including PSSM2, MFM and MIM, BEVA does not recommend them.

Prof Piercy said: “The results offered have not, to our knowledge, been scientifically validated in any peer-reviewed literature or shared in any form with the scientific community.

“In short, there is no evidence that the offered tests identify mutations that actually cause muscle disease or indeed, are associated with disease in any way at all.”

Speak to vets

Prof Piercy said it was vital owners were encouraged to speak to their vets about the evidence basis for investigating myopathies in horses.

He added: “Until results of genetic testing for PSSM2, MFM, MIM and other myopathies in horses are presented in peer reviewed, validated scientific literature that is accepted by the scientific community (as has been the case for PSSM1), we do not recommend their use and certainly do not support veterinary or life decisions being made based on their results.”

Two US papers^3,4 found no association between PSSM2 (or any other muscle disease) and the genetic variants offered by the testing companies.

References

1. McCue ME et al (2008). Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis, Genomics  91(5): 458-466.

2. Maile CA et al (2017). A highly prevalent equine glycogen storage disease is explained by constitutive activation of a mutant glycogen synthase, Biochim Biophys Acta Gen Subj 1861(1 Pt A): 3,388-3,398.

3. Valberg SJ et al (2021). Commercial genetic testing for type 2 polysaccharide storage myopathy and myofibrillar myopathy does not correspond to a histopathological diagnosis, Equine Vet J 53(4): 690-700.

4. Valberg SJ et al (2023). Absence of myofibrillar myopathy in Quarter Horses with a histopathological diagnosis of type 2 polysaccharide storage myopathy and lack of association with commercial genetic tests, Equine Vet J 55(2): 230-238.