Understanding Fragile Foal Syndrome

Symptoms, Causes, Diagnosis, Treatment & Prevention

Some of you may remember when alarm bells suddenly rang a few years ago in the horse community when an unfortunate birth in the warmblood world shined a spotlight on the existing (but stealth) issue of what was then referred to as “Warmblood” Fragile Foal Syndrome (FFS). Given the concern and rise in testing, the team at Etalon Equine Genetics gathered their research data together and provided an eye-opening publication showing that the term “Warmblood” Fragile Foal Syndrome was misleading…we found genetic evidence of FFS in many common breeds! Shortly thereafter, other groups also published similar findings and followed Etalon’s lead in officially renaming this miserable condition, “Fragile Foal Syndrome.”

So what is FFS really and what can be done about it? Read on, dear horse person, and let’s explore what Fragile Foal Syndrome is, the importance of genetic testing, and the best approaches for preventing this disorder in the future.

What is Fragile Foal Syndrome?

Fragile Foal Syndrome is a hereditary connective tissue disorder that is caused by a genetic mutation. You may have previously heard the condition referred to as “Warmblood” Fragile Foal Syndrome due to its association with Warmblood horses when the original discovery was announced in 2015 following the study of a foal born in 2012. “Warmblood” was dropped from the name when Etalon’s research showed that this inherited genetic defect is present in a variety of horses of other breeds.¹

Rarely are FFS foals born alive. Because of this, it is hypothesized that FFS has largely gone undetected because many affected foals are aborted by their dams. For the incredibly few foals that do make it to term, FFS causes them to be born with extremely thin skin that is only loosely connected to the body and joint laxity. The skin is easily torn, resulting in lacerations, hematomas, and seromas across the foal.

FFS is an autosomal recessive disorder, meaning horses must inherit two copies of the FFS allele (ffs/ffs) to show the disease. Horses with only one allele (ffs/n) are known as carriers due to their ability to produce affected offspring.

Common symptoms of Fragile Foal Syndrome include:

• Thin skin
• Hyperextensible skin
• Hyperextensible joints
• Abnormally floppy ears
• An overaccumulation of placental fluid
• Subcutaneous emphysema - air trapped under the subcutaneous layer of skin
• Hematomas
• Seromas
• Premature birth
• Stillbirth

What causes Fragile Foal Syndrome?

Fragile Foal Syndrome is caused by a mutation in the PLOD1 gene. The PLOD1 gene codes for an enzyme that is necessary for processing collagen, the most abundant protein in the body. Collagen gives structure, strength, and support to many of the body’s tissues, such as the skin, bones, muscles, tendons, and cartilage.

The mutation of the PLOD1 gene that causes FFS hinders the normal function of the enzyme it is associated with. This causes the horse’s body to synthesize collagen improperly which impacts the overall strength of the collagen fibers. Due to the vital nature of collagen, this impairment results in the debilitating symptoms associated with the disease. Mutations of the PLOD1 gene are also seen in humans with a disease known as Ehlers-Danlos Syndrome Type VI which is characterized by similar symptoms.

FFS is often compared to Hereditary Equine Regional Dermal Asthenia (HERDA) because they are both recessive genetic mutations that are related to collagen in the body, resulting in similar symptoms. Where FFS and HERDA differ, however, is that HERDA is caused by a mutation of the PPIB gene and is seen in stock-type horses such as Quarter Horses, Appaloosas, and Paints.

How is Fragile Foal Syndrome diagnosed?

The most accurate way to diagnose FFS is through genetic testing. Because the clinical symptoms of FFS present similarly to other diseases such as HERDA, physical examination and necropsy are not enough to diagnose the condition.

It is believed that most foals who have FFS are aborted early in the pregnancy, and never get the chance to be diagnosed with the condition. This is why genetic testing of the sire and dam prior to breeding is so important to mitigate the number of foals lost. The cost of testing before breeding is minimal compared to the financial and emotional costs associated with caring for a Fragile Foal.

How is Fragile Foal Syndrome treated?

Unfortunately, there are currently no treatment options for horses afflicted by FFS at this time due to the severity of the condition. Because of this, affected foals are typically humanely euthanized shortly after birth. Using statistics, based on how many known and estimated carriers are currently in the horse world, we can further surmise that many more FFS foals are never carried to term, but, rather, are lost in failed pregnancies.

At this time, there is no indicated treatment for carriers of FFS as it is not deemed necessary.

Can Fragile Foal Syndrome be prevented?

FFS is an inherited disease, and it is best prevented by investing in genetic testing before breeding a horse, regardless of its breed and ancestry. Based on the results of testing, the best way to minimize the risk of producing a foal with FFS is achieved by selectively breeding an FFS carrier to an FFS non-carrier or even potentially choosing to not breed a carrier horse at all if the status of the other horse is unknown.

How can I test to see if my horse is a carrier of Fragile Foal Syndrome?

The only way to know for sure if your horse is a carrier of FFS is through genetic testing. Etalon Equine Genetics offers testing for FFS as an individual test and is included in our most comprehensive genetic testing panel.

What will my horse’s results look like?

There are 3 possible test outcomes:

n/n or negative - Non-carrier, non-affected. Unable to pass FFS to any offspring.

ffs/n - Carrier; one allele detected. Currently no known effect. Can pass one FFS allele to 50% of any offspring.

ffs/ffs - Affected. Foal may be aborted, stillborn or born with lesions and thin skin resulting in death.

Implications for Fragile Foal Syndrome Carriers

While it was previously believed that carriers of FFS do not exhibit symptoms of the disorder, recent studies using artificial intelligence (AI) technology have shown that may not actually be the case.

The first study assessed the conformational differences between the necks, forelimbs, and hindlimbs of FFS and non-FFS carrier horses. Initial results showed that FFS carriers had longer measurement lengths across all three examined areas compared to the non-FFS carriers.²

The second study looked to assess the gait quality of FFS versus non-FFS carrier horses. The results of this study showed that “FFS carriers had a greater extension and swing of all 4 limbs,” resulting in “an altered hoof flight path throughout the stride cycle.” ³

These preliminary findings lend themselves to the theory that there could be more FFS carrier horses out there than we realize as more and more horses are being bred to be hypermobile. This hypermobility results in what appears to be flashier movement due to an increased range of motion, which is especially sought after and even selectively bred for in some disciplines such as dressage.

It has also been theorized that carriers of the FFS mutation might also be more likely to experience soft tissue injury later in life because the disease is related to collagen, which is the main component of all connective tissues. So far, there is little scientific evidence to prove this theory. One study from 2020 examined 716 Thoroughbreds and found that out of the 22 horses that experienced “catastrophic breakdown,” though only one was a FFS carrier.⁴ The horses evaluated in this study were all relatively young, however, so it does not definitively rule out the theory that FFS carrier horses may experience soft tissue injuries as they age. Future research is needed to answer these questions.

Fragile Foal Syndrome is a recessive genetic disorder that is caused by a mutation of the PLOD1 gene, which affects the horse’s ability to process collagen. It causes horses to be born with extremely thin and easily torn skin, and rarely are FFS foals born alive. There is no treatment for horses that are affected by FFS, so genetic testing of sires and dams before breeding is strongly recommended to minimize the risk of producing a foal with two copies of the FFS gene. Recent studies using artificial intelligence technology have also shed light on the idea that there may be more FFS carriers out there than we realize, potentially linked to the desire to selectively breed for a more hypermobile horse. Protecting the future of the equine industry is in our hands, and testing for FFS is a critical component of responsible breeding.

References

¹ Martin, K., Brooks, S., Vierra, M., Lafayette, W. T., McClure, S., Carpenter, M., & Lafayette, C. (2021). Fragile Foal Syndrome (PLOD1 c.2032G>A) occurs across diverse horse populations. Animal Genetics, 52(1), 137-138. https://doi.org/10.1111/age.13020

² Rahael, H., Smythe, M., Dewberry, S., Oberdorfer, A., Allen, K., & Brooks, S. (2023). 44 Detecting conformational differences in Fragile Foal Syndrome carriers utilizing artificial intelligence. Journal of Equine Veterinary Science, 124, 104346. https://doi.org/10.1016/j.jevs.2023.104346

³ Smythe, M., Dewberry, S., Staiger, E., Allen, K., & Brooks, S. (2023). 45 Quantifying gait quality changes in fragile foal syndrome carriers using artificial intelligence. Journal of Equine Veterinary Science, 124, 104347. https://doi.org/10.1016/j.jevs.2023.104347

⁴ Bellone, R. R., Ocampo, N. R., Hughes, S. S., Le, V., Arthur, R., Finno, C. J., & T. Penedo, M. C. (2020). Warmblood fragile foal syndrome type 1 mutation (PLOD1 c.2032G>A) is not associated with catastrophic breakdown and has a low allele frequency in the Thoroughbred breed. Equine Veterinary Journal, 52(3), 411-414. https://doi.org/10.1111/evj.13182