Is it Genetic? What Truly Lies in a Horse's Genes – and What is Merely Claimed

This article was translated using AI.

Key Points at a Glance

• A genetic disease and a genetic predisposition are two completely different things: In a disease, a single gene alteration causes the illness; in a predisposition, many genes only shift the probability – management, feeding, and environment are the deciding factors.
• There are a number of true, monogenic hereditary diseases in horses that are closely linked to certain breeds and sometimes even color patterns – from HYPP in Quarter Horses to Lethal White Syndrome in Overo paints.
• For some conditions, a hereditary predisposition is well-documented without being monogenic – summer eczema (sweet itch) is the best-known example.
• In others, a genetic predisposition is suspected, but the responsible gene has not been found to date – such as in Chronic Progressive Lymphedema in draft horses, which underlies the classic susceptibility to scratches (pastern dermatitis) in Belgian bloodlines.
• Genetic tests marketed as “PSSM2” or “MIM tests” have shown no correlation in independent studies with the disease they promote – the tested variants occur just as frequently in healthy horses.
• A genetic test is only as good as the science behind it. When you hear “genetic,” you should ask: proven disease, documented predisposition, or mere claim?

Three Things That Are Constantly Confused

“Your horse is genetically burdened.” Hardly any sentence causes as much confusion – and as much misinformation. Behind it can lie three fundamentally different scenarios that are frequently mixed up in everyday life, in sales pitches for genetic tests, and in Facebook groups alike.

The first is the true genetic disease in the narrow sense. It is usually monogenic, following Mendelian rules: a defined change in a single gene causes a defined disease. Whoever carries the corresponding gene copies develops the disease – with one copy in dominant inheritance, with two in recessive – largely independent of how the horse is kept and fed. Here, a genetic test is actually a diagnosis.

The second is genetic predisposition, and it is something completely different. It is multifactorial: usually, several genes each contribute a small part, and in total, they merely shift the probability that a disease will occur. Whether the horse actually becomes ill and how severe the disease turns out to be is decided by the environment – feeding, management, exercise, metabolism. A genetic test here can at best quantify a risk, but never provide a diagnosis.

The third is the most sensitive case: the claimed but unproven genetic cause. Here, a connection between a gene and a disease is sold that independent research cannot confirm. This category includes the much-discussed “PSSM2” or “MIM tests,” which we will discuss in detail below.

This article provides an overview: of confirmed hereditary diseases, documented and suspected predispositions, and the tests that promise more than they deliver – and finally, the question of what daily practice with the horse contributes that no laboratory can answer.

Confirmed Hereditary Diseases

Let's start with the cases where everything is clear: a single gene, a known mutation, a traceable inheritance pattern. These diseases are often closely linked to individual breeds because they have spread through a few, heavily used breeding lines. A licensed genetic test is useful here and valuable for breeding decisions in order to eliminate the “hereditary disease” in the long term.

Regarding the musculoskeletal system, muscle diseases are of particular importance. Hyperkalemic Periodic Paralysis (HYPP) is due to a change in the sodium channel gene SCN4A, is inherited semidominantly, and is found in Quarter Horses of the Impressive line as well as in Paints and Appaloosas with corresponding ancestry; affected horses show muscle tremors, weakness, and, in the worst case, life-threatening cardiac arrhythmias.

Polysaccharide Storage Myopathy Type 1 (PSSM1) is based on a mutation in the glycogen synthase gene GYS1, is inherited dominantly, and affects many Draft and Quarter Horse lines; here, abnormal glycogen accumulates in the muscles, leading to episodes similar to tying-up (exertional rhabdomyolysis).

Malignant Hyperthermia is a dominant change in the ryanodine receptor RYR1 of the Quarter Horse, which becomes dangerous primarily under anesthesia. Immune-Mediated Myositis (MYHM) via the MYH1 gene causes muscle wasting in Quarter Horses following an infection. And the glycogen branching enzyme deficiency (GBED) via the GBE1 gene is recessive and fatal for affected Quarter Horse and Paint foals.

The skin and connective tissue are also affected. Hereditary Equine Regional Dermal Asthenia (HERDA) is based on a recessive change in the gene for cyclophilin B (PPIB) and occurs primarily in cutting lines of the Quarter Horse; the skin of these horses is hyperextensible and tears easily. Warmblood Fragile Foal Syndrome (WFFS) via the collagen gene PLOD1 is recessive and leads to extremely fragile skin in affected foals. Junctional Epidermolysis Bullosa (JEB) occurs in two separate forms: in Belgian and related Draft horses via an insertion in the LAMC2 gene, and in American Saddlebreds via a deletion in the LAMA3 gene – both are recessive and fatal for foals because the skin detaches over large areas.

In the immune system, Severe Combined Immunodeficiency (SCID) in Arabians is noteworthy – a recessive, usually fatal disease in which affected foals are born practically without a functioning immune defense. Neurologically, Arabians are known for Cerebellar Abiotrophy via the TOE1/MUTYH gene region – a progressive loss of coordination in foals – and Lavender Foal Syndrome via the MYO5A gene, which combines a pale coat color with severe neurological disorders.

Particularly instructive are the cases in which color and disease reside in the same gene. Our ancestors did not say without reason: A good horse has no color. Today's enthusiasm for colorful horses clearly demonstrates the risk that arises when breeding for original colors instead of health.

The best-known example is Overo Lethal White Syndrome: The homozygous form of the frame overo pattern via the endothelin B receptor EDNRB leads to foals being born white and dying within hours from a non-functional, nerve-less segment of the intestine. The grey color itself is linked to a significantly increased risk of melanoma.

The Silver gene (PMEL) can be associated with congenital eye malformations (MCOA) and occurs primarily when breeding for the “silver dapple” (Windfarbe) coveted in Icelandics, or “chocolate dapple” in the Rocky Mountain Horse, which combines a dark brown or dark grey coat with flaxen mane and tail. The leopard complex spotting, so coveted in Knabstruppers and Appaloosas, is often associated with congenital night blindness via the TRPM1 gene. And certain splashed white patterns, which are particularly popular in Paints and Appaloosas, can be linked to deafness.

A beautiful color variant is not always beautiful for the horse. Therefore, not only breeders but also potential buyers of such horses should inform themselves in advance about possible genetic defects.

Documented Predisposition: Summer Eczema

Now, the step from genetic disease to genetic predisposition. Summer eczema – professionally known as Insect Bite Hypersensitivity (IBH) – is an allergic skin inflammation reacting to the saliva of biting insects, primarily midges (Culicoides). And it has a hereditary component; this is well-documented.

In Icelandic horses, heritability was estimated at around 0.3 (Eriksson et al. 2008), and even higher in Belgian Warmbloods on the underlying scale. In the immune-regulating gene region MHC or ELA, variants were found that are linked to the disease in two separate populations with the same risk variant (Andersson et al. 2012, Klumplerova et al. 2013). So, there are demonstrably families and lines that are more susceptible than others.

But – and here lies the crucial point – the same figure that proves heritability also debunks the common short-circuit logic of “it's genetic, so nothing can be done.” A heritability of 0.3 also means that around 70 percent of the differences between horses are not in the genes but in everything else: in the insect pressure of the location, in management, in metabolism, in feeding. Predisposition loads the gun, but the environment pulls the trigger.

Suspected Predisposition: Scratches and CPL in Draft Horses

There is a third group that is particularly exciting for practice: diseases where everything points to a hereditary predisposition, but the responsible gene has not been found to date. The best example is also the answer to an old observation from draft horse stables – the striking susceptibility to scratches (pastern dermatitis) in certain lines.

In many cases, this is due to Chronic Progressive Lymphedema (CPL). It is based on a disorder of lymphatic drainage in the lower limbs with progressive fibrosis, skin folds, nodules, and a disturbed elastin framework of the skin, and it is documented in Belgians, Shires, Clydesdales, and numerous other draft horse breeds. In a study on Belgian Draft horses, a prevalence of around 86 percent was reported (De Keyser et al. 2014), and certain bloodlines are more affected than others. This also coincides with the experience that the tendency toward stubborn scratches migrated into German draft horse breeds through the crossbreeding of certain Brabanters (Belgian Drafts).

That a genetic basis exists is considered very likely: CPL occurs practically only in related draft horse breeds, clusters in families, and cannot be completely prevented by even the most optimal management. A whole-genome analysis of German draft horses narrowed down gene regions associated with chronic pastern dermatitis (Mittmann et al. 2010). However, the obvious candidate gene FOXC2, which causes a comparable lymphedema disease in humans, was sequenced and ruled out as the cause (Towers et al. 2013). Thus, it is known that it is very likely inherited – but not which gene is responsible for it. This makes CPL a prime example of a suspected but unresolved genetic predisposition.

Important for classification: Scratches (pastern dermatitis) itself is not a hereditary disease. It has many possible causes – wetness, bacteria, the mange-causing mite Chorioptes, lack of hygiene, feeding errors, detoxification disorders, and others. The heavy feathering of draft horses also creates a warm, moist environment in which pathogenic germs can easily establish themselves. What is inherited in the draft horse is not the scratches, but the susceptibility of the tissue on which they thrive particularly well.

When Genetic Testing Promises More Than Science Knows

This brings us to the heart of the confusion: the genetic tests sold as “PSSM2 tests” and later as “MIM tests” (for Myofibrillar Myopathy). They promise to diagnose a muscle disease based on a few gene variants. A commercial laboratory has been offering them since 2016. One must know that veterinary genetic testing is not government-regulated – anyone can offer a test without any independent verification.

Variants are tested in three genes, all of which are responsible for structural proteins of the so-called Z-disc in the muscle: Myotilin (referred to as “P2,” gene MYOT), Filamin C (“P3,” gene FLNC), and Myozenin 3 (“P4,” gene MYOZ3). These proteins keep the contractile apparatus of the muscle cell in shape. The idea behind it sounds plausible at first – in humans, mutations in related Z-disc genes can indeed cause muscle diseases.

However, the claimed connection could not be confirmed in horses. The working group led by Stephanie Valberg, one of the world's leading myopathy researchers in the equine field, has examined the variants. In Warmbloods and Arabians clearly diagnosed as PSSM2 or MFM cases via muscle biopsy, the tested variants occurred no more frequently than in healthy control horses of the same breed; the very low hit rate means that the variants cannot indicate the disease (Valberg et al. 2021). In a second study, the result for Quarter Horses was exactly the same – and the affected horses did not even show the histopathological features of MFM (Valberg et al. 2023). The researchers' conclusion is unmistakable: these genetic tests are suitable neither for diagnosis nor for breeding selection or pre-purchase examinations.

The reason why such tests still turn out “positive” so often is obvious: the tested variants are widespread in the normal, healthy horse population. A “positive” result is therefore the rule, not the exception – and it says nothing about the cause of any symptoms.

What Practical Experience Tells Us

At this point, it is worth looking outside the research laboratory and the experimental stable, at what is not in any study. Summer eczema was long considered a kind of “Icelandic genetic defect” – an idea that is obvious because the breed is strikingly often affected and the disease clusters in certain lines. In the meantime, however, we see summer eczema in all sorts of breeds, from Warmbloods to ponies. If it were a simple genetic defect of one breed, that shouldn't happen. There must be more at play than just a hereditary predisposition.

Particularly revealing is a development that people in the Icelandic horse scene are reluctant to talk about: summer eczema is now also occurring in Iceland itself – and without the midges that never existed there in significant numbers. What has changed in Iceland is not the insect fauna, but the feeding: where sparse forage used to be the rule, haylage and muesli are now on the menu. Anyone who knows the connections between feeding, gut health, and excessive immune reactions is not surprised. It fits the picture that a sensitized metabolism makes the skin more susceptible – even if the classic trigger is missing.

The situation is similar with supposedly “MIM-positive” horses. The vast majority presented with this label do not carry their actual problem in the Z-disc of the muscle cell, but in their metabolism: they are disproportionately often insulin resistant. And insulin resistance – unlike a hereditary disease – is generally not inherited, but “fed into existence” over years, very similar to type 2 diabetes in humans. If you change the diet, ensure that the muscles respond to insulin again, and the metabolism settles down, the symptoms disappear – in a horse whose gene variants cannot be changed by any diet in the world. A clearer argument against the genetic misdiagnosis is hard to find.

This is not hostility toward science, on the contrary. It is the supplement that the laboratory finding needs: Genetics says what is possible. Practice sees what actually happens – and in what order.

What a Genetic Test Can and Cannot Do

So, what does a genetic test for my horse provide? A genetic test is a powerful tool – for the right question. In a confirmed, monogenic hereditary disease such as HYPP, PSSM1, or JEB, it provides a real diagnosis and is indispensable for breeding decisions, especially in recessive inheritance, because it prevents two outwardly healthy carriers from being mated and producing sick foals.

In a predisposition, a test can at best indicate a risk – and even then only if the underlying research is sound. It never replaces looking at management, feeding, and metabolism, because that is where it is decided whether a predisposition becomes a disease.

And in the case of a test whose connection with the advertised disease is not independently proven, caution simply applies. A “positive” result that occurs in half of all healthy horses is not a diagnosis, but a number without meaning.

The next time you hear that a horse is “genetically burdened,” you are welcome to ask: Is it a confirmed hereditary disease, a documented predisposition, or a mere claim? The answer determines whether you are dealing with a fate, a risk, or a misunderstanding – and whether the actual solution might not lie in the laboratory, but in the feed bucket.

Sources

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Cappelli, K., Brachelente, C., Passamonti, F., Flati, A., Silvestrelli, M., Capomaccio, S. (2015): First report of junctional epidermolysis bullosa (JEB) in the Italian draft horse. BMC Veterinary Research 11:55. DOI: 10.1186/s12917-015-0374-0

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Klumplerova, M., Vychodilova, L., Bobrova, O., Cvanova, M., Futas, J., Janova, E., Vyskocil, M., Vrtkova, I., Putnova, L., Dvorakova, L., Marti, E., Horin, P. (2013): Major histocompatibility complex and other allergy-related candidate genes associated with insect bite hypersensitivity in Icelandic horses. Molecular Biology Reports 40(4):3333–3340. DOI: 10.1007/s11033-012-2408-z

Mittmann, E. H., Mömke, S., Distl, O. (2010): Whole-genome scan identifies quantitative trait loci for chronic pastern dermatitis in German draft horses. Mammalian Genome 21(1–2):95–103. DOI: 10.1007/s00335-009-9244-z

Towers, R. E., Murgiano, L., Millar, D. S., Glen, E., Topf, A., Jagannathan, V., Drögemüller, C., Goodyear, M. J., Fen Foo, I., Straub, R., Leeb, T., Elphick, M. R., Tervoort, T., Turner, E. C. (2013): Evaluation of FOXC2 as a candidate gene for chronic progressive lymphedema in draft horses. [Marked for DOI verification before publication.]

Valberg, S. J., Henry, M. L., Perumbakkam, S., Gardner, K. L., Finno, C. J. (2021): Commercial genetic testing for type 2 polysaccharide storage myopathy and myofibrillar myopathy does not correspond to a histopathological diagnosis. Equine Veterinary Journal 53(4):690–700. DOI: 10.1111/evj.13345

Valberg, S. J., Finno, C. J., Henry, M. L., Schott, M., Velez-Irizarry, D., Peters, D., Gardner, K., Chartier, M. (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 Veterinary Journal 55(3):506–515. DOI: 10.1111/evj.13574