MIM-6-Var. Test (formerly PSSM2)

The predictive value of tests for risk factors associated with multifactorial diseases, such as the MIM test for exertional myopathy, must not be equated with test results for monogenic hereditary disorders.

Misinterpretations arise when an analogous mutation–effect relationship is expected.

This leads to statements such as “the diagnostic value is insufficient” or “the MIM test is not validated” when, for example, a horse shows clinical signs of exertional myopathy despite testing n/n (no mutation detected) for all tested MIM/PSSM variants.

Therefore, it is important to understand that the MIM test is not a diagnostic test.

Rather, the test assesses whether a horse possesses a genetic predisposition that may increase its risk of developing the disease.

Different criteria therefore apply to such risk-factor tests than to tests used for evaluating monogenic hereditary diseases.

The examples below are intended to help you apply these tests correctly for the benefit of your animals.

If the test were (incorrectly) classified as a diagnostic test, the inevitable conclusion would be that it is unable to reliably identify clear clinical cases.

The correct interpretation would be: the tested variants are not present in the examined animal and cannot be contributing to the current clinical signs.

The causes must therefore lie within other factors, such as nutrition, management, training, stress, unknown genetic situations, infections, intoxications, injuries, or environmental influences. These are the areas that should now be investigated in order to determine the underlying cause(s) of the symptoms.

Importantly, the situation provides a good basis for improving the clinical signs through adjustments in feeding and management. Veterinary supervision to investigate the underlying causes, together with consultation from a specialized equine nutrition advisor (link), would be recommended.

From the perspective of a “monogenic” interpretation, this would be considered a false-positive test result, and the test would therefore be classified as “not diagnostically useful.”

The correct interpretation, however, is: the test result demonstrates that the examined horse carries genetic factors that predispose it to developing clinical signs of exertional myopathy.

The presence of these variants initially means only that the horse has a different inherited genetic background — not that it is necessarily diseased.

Importantly, knowledge about the extent of this predisposition can be used to optimize the other risk factors, such as nutrition, housing, training, and stress management. When these factors are well controlled, such horses can often be used without limitations. Particular attention should be paid to maintaining optimized nutrition and appropriate training after a sporting career or following changes in housing or management conditions.

In this situation, the clinical signs and DNA test results would appear to correspond in a diagnostic sense. However, it must be respected that only some of the genetic components of the condition has been evaluated.

A comprehensive assessment should take into account that, despite the presence of the detected variants, additional factors may contribute to the observed clinical signs. These factors may act individually or reinforce one another. They include age-related impairment of protein quality control, deficiencies of minerals or trace elements, inappropriate nutritional composition, unsuitable training, and stressful situations (e.g. surgery or relocation). These are also the areas where supportive countermeasures should be directed.

Depending on the extent of the genetic predisposition, optimization of these additional factors (link) can often result in a remarkably improved clinical outcome.