Warmblood Fragile Foal Syndrome (WFFS) is an inherited disease primarily affecting Warmblood horses and their related breeds. This condition is also referred to as Fragile Foal Syndrome Type 1 (FFS).

WFFS is characterized by the production of defective collagen, which compromises the integrity of connective tissues. This defect primarily affects the skin, ligaments, and tendons, making them prone to injury and damage.

There is no treatment for WFFS. Foals born with two copies of the gene mutation responsible for WFFS are non-viable and die during gestation or shortly after birth. Foals with one copy of the gene do not exhibit symptoms but are carriers of the disease and can pass it on to their offspring.

WFFS is a relatively new disease, and a genetic test for the condition was only developed in 2011. [1] Research is ongoing to determine how the disease affects carrier animals, what breeds of horses are affected, and the original source of the gene mutation that causes the disease.

Warmblood Fragile Foal Syndrome

WFFS occurs due to a mutation in a gene called PLOD1 (procollagen-lysine, 2-oxoglutarte 5-dioxygenase1). This gene is involved in the synthesis of collagen, a major component of connective tissue. [1]

A mutation in the PLOD1 gene is also a known cause of Ehlers-Danlos Syndrome in humans, which is a condition of hyperelasticity affecting the skin, joints, and blood vessels. [1]

The normal function of the PLOD1 gene is crucial for crosslinking collagen fibrils, which provide structural strength to collagen. The defective gene results in collagen that is unstable. [2] The unstable collagen is very thin, brittle and fragile, which makes the tissues it supports prone to damage. [2]

Common tissues where collagen is a structural component include:

  • Skin
  • Blood vessels
  • Joint capsules

Inheritance Pattern

The PLOD1 gene has an autosomal recessive inheritance, which means that both parents must carry a copy of the gene to pass it along to a foal. [1]

When breeding two carriers, there is a 25% chance of the foal inheriting both copies. [1] There is also a 50% chance of the resulting foal being a carrier for the disease, who can pass the gene onto their foals.[1]

Affected Breeds

As the name suggests, WFFS primarily affects Warmblood horses, however it has been reported in other breeds. Examples of warmblood breeds include:

Many of the non-warmblood breeds with carriers are breeds derived from warmbloods or that allow warmblood crosses, such as the American Sport Pony and Knabstrupper. [3]

For these breeds, researchers presume that the mutation entered the breed from a warmblood carrier, rather than these breeds developing their own mutation.

Thoroughbreds

Thoroughbreds are common in warmblood pedigrees, as this breed was the foundation for many of the warmblood types. Originally, there was speculation that WFFS originated from the Thoroughbreds used in warmblood development, as many of the affected horses had pedigrees going back to Dark Ronald xx.

Although research has identified several WFFS carrier Thoroughbreds, studies show that carriers are uncommon overall in this breed. [4]

There is some speculation that the low prevalence of WFFS in Thoroughbreds is due to breeders selecting for racing performance, rather than the dressage and jumping-based performance, which Warmbloods are selected for. [4]

Therefore, WFFS-carrying Thoroughbreds may have been eliminated from racing breeding, but were still popular for use in Warmblood breeding, and introduced the mutation into warmblood breeds.

Other Breeds

Some breeds unrelated to warmbloods have also identified WFFS carriers. These breeds include: [3] [5]

Pedigree Analysis

Since the disease is inherited from the foal’s parents, researchers are currently conducting pedigree analyses of affected foals to try and identify commonly affected bloodlines. [1]

Many other genetic diseases of horses, such as hyperkalemic periodic paralysis (HYPP) in Quarter Horses, have a single common ancestor attributed to the disease. It is yet to be determined whether this is true for WFFS.

Current speculations on common ancestors or bloodlines include:

  • An unnamed Hanoverian stallion. Based on evaluation of 76 carriers, one Hanoverian stallion born in 1861 was identified as a common ancestor. This stallion was from the F/W line of Hanoverians, which contributed heavily to dressage breeding lines. [6]

Research has also ruled out some previously speculated bloodlines, including:

  • Dark Ronald, or his father, Bay Ronald, Thoroughbred stallions that heavily influenced both German Thoroughbred and Warmblood breeding. Preserved skin samples of Dark Ronald did not test positive for WFFS. [7]
  • Bairactar, an Arabian stallion commonly found in the pedigree of European Sport Horses. There are reports from 1855 of horses inbred to Bairactar having a condition similar to WFFS. [1] A tooth from Bairactar’s remains preserved in a m