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SPECIAL REPORT ROLLING THE DICE: Genetics is an odds game Genetic Disease Strikes the Warmblood Breeds Little known until this year, warmblood fragile-foal syndrome is rocking the sport-horse world. An overview of WFFS and how breeders are fighting back. BY HEATHER SMITH THOMAS lthough horse people have known for decades Advocates say that warmblood breeders, buyers, and regis- that some breeds are affected by genetic diseas- tries alike need to educate themselves about WFFS and to es, the sport-horse industry has been content take steps to halt its spread. Read on for an overview of the in the knowledge that the warmblood breeds disorder and a look at how breeders are responding. are free from such disorders. Genetics 101 AUntil this year. The case of a Texas foal born with the almost unheard-of To understand what WFFS is and how it proliferates, start disease called warmblood fragile-foal syndrome (WFFS), a with this genetics refresher. severe genetic defect, led to the realization that this “sleep- The color of your eyes and your horse’s coat color are er” disorder has actually been lurking in some warmbloods’ examples of genetic traits, or inherited characteristics. Ge- DNA for over 100 years. (See “The Foal That Changed the netic diseases, like genetic traits, are passed on to the off- Warmblood World” on page 37.) spring from one or both parents. Sport-horse breeders and veterinary researchers are Some genetic traits are dominant, while others are re- SHUTTERSTOCK working to publicize the issue and to effect industry change. cessive. A dominant trait is passed directly from parent USDF CONNECTION • December 2018/January 2019 35 TELLTALE SIGNS: The skin of foals with warmblood fragile-foal syndrome tears abnormally easily (left). Affected foals’ joints are so lax that they are unable to stand (right). to offspring. A recessive trait appears only if both parents gional dermal asthenia (HERDA), causes skin fragility and is not only carry that recessive gene, but also pass it to the found primarily in some lines of American Quarter Horses offspring. That’s why a recessive trait may “hide” for many that trace back to a popular stallion that originated the defect. years and suddenly appear as if out of nowhere, like the sur- “One thing HERDA taught us,” says Winand, “is that prise of a red-headed baby born into a brown-haired family. recessive traits may exist in horse populations for decades Genetic diseases or defects result from gene mutations. before they are recognized as a problem.” Mutations occur from time to time as species reproduce, In 2007, a veterinary researcher at the University of and “there is no way to avoid them, so it is important to stay Guelph in Canada contacted Winand and her Cornell col- on top of them,” says retired Cornell University veterinary league William H. Miller Jr., VMD, a professor of veterinary molecular geneticist Nena Winand, DVM, PhD. But that’s dermatology, about a Hanoverian foal that had been pre- hard to do when the genetic disease is recessive. “By the sented for necropsy to a Canadian laboratory. The foal had time a recessive genetic defect is recognized,” she explains, suffered from a strange combination of severe defects: ex- “carrier status for the trait may have already become wide- treme joint laxity and skin that tore like tissue paper at the spread in breeds or closed breeding populations.” slightest touch. The dead foal’s breeder provided blood samples from WFFS Explained the sire and dam and from other horses at the facility. “I processed the blood samples for DNA isolation,” says Wi- WFFS is a recessive genetic disease that manifests as a con- nand, “but this project had to stay on the back burner be- nective-tissue disorder in affected warmblood foals. WFFS cause it didn’t give me an avenue to study anything. This foals have extremely fragile skin that lacks normal durabil- material stayed in the freezer a long time.” ity and strength, tearing or ulcerating at the lightest contact. The samples came out of the freezer in a hurry in 2011, In addition, their limb joints are so abnormally lax that they when Winand and Miller got a call from the Wisconsin cannot stand. Mares frequently abort WFFS foals, but those Equine Clinic & Hospital in Oconomowoc, Wisconsin, that are carried to term must be euthanized soon after birth. about a warmblood foal that it had just euthanized. The foal Veterinary researchers and warmblood breeders are had been born with the same set of gruesome defects as the beginning to connect the dots between WFFS and foal Canadian Hanoverian foal. loss in the warmblood breeds, says Duncan Peters, DVM, Provided with tissue material from the dead Wisconsin DACVSMR, founder and co-owner of East-West Equine foal, Winand set to work. Within 24 hours, she says, she had Sports Medicine in Lexington, Kentucky, and resident vet- identified a “devastating” homozygous mutation in a gene. erinarian/consultant for the Lexington-based sport-horse The stallion owners refused to provide Winand with DNA breeding facility Spy Coast Farm. material, she says, but she was able to obtain a blood sample “Some mares that suffer early pregnancy loss or abort from the dam. may have this condition,” Peters says, meaning that they “The dam was heterozygous for that mutation, which may be WFFS carriers. “Some of the warmblood-breeding means it was probably a recessive trait that had to come operations are starting to look into this, checking back from both parents,” she says. through their breeding records to figure this out.” Winand then tested her stored samples provided by How Was WFFS Discovered? the Canadian Hanoverian breeder. “Sure enough, both the sire and dam of that foal were carriers of the same muta- In the 1990s and early 2000s at Cornell, Winand was re- tion—evidence that this mutation is causing the very severe searching various hereditary genetic defects in equines and connective-tissue fragility,” she says. other species, including humans. One, hereditary equine re- Winand had to do a deep dive into equine family trees to COURTESY OF DR. NENA WINAND 36 December 2018/January 2019 • USDF CONNECTION try to identify the origin of the WFFS mutation. She eventu- A WFFS carrier has one normal gene and one recessive, ally concluded that the most likely source was a French Thor- abnormal gene. If a WFFS carrier is bred to a non-carrier, the oughbred stallion (whose name she declines to mention) offspring will be normal because it has inherited a normal gene “that was used in France and Germany to upgrade the war- from the non-carrier parent. However, the odds are 50/50 that horse types of horses being used in the mid-1800s. This was that same offspring will be a carrier of the WFFS gene. the only common link, but that stallion was used widely…and It’s a different story when a WFFS carrier is mated with is in the bloodlines of many [warmblood] registries.” another WFFS carrier. When that happens, there are three possible outcomes. The offspring can be: Rolling the Genetic Dice: 1. Normal but a WFFS carrier (50 percent chance) How WFFS Is Inherited 2. Normal and not a WFFS carrier (25 percent chance) 3. Afflicted with WFFS as a result of inheriting the -ab To geneticists, a carrier is an individual that possesses an un- normal gene from both parents (25 percent chance). expressed, recessive trait or defective gene. In other words, a carrier can pass the recessive gene on to its offspring but Breeders Confront the Disease itself does not have the trait or defect. That’s why it’s taken researchers a while to get a handle on WFFS—because carri- Many sport-horse enthusiasts learned of WFFS in April ers look and act like every other normal, healthy warmblood 2018, when the well-known breeding facility Hilltop Farm, sport horse. In fact, some known carriers are top performers, Colora, Maryland, announced that its Hanoverian stallion both in the dressage arena and as breeding stock. Sternlicht Hilltop (Soliman de Hus – EM Rhapsody GGF, WFFS is a recessive trait, meaning that both parents Rascalino) is a WFFS carrier. While the farm did further must carry the defective gene in order for it to be passed investigation into WFFS, Hilltop was removing Sternlicht on to the foal. But even when that happens, the foal doesn’t from its breeding roster for the remainder of 2018, manag- always have WFFS. Here is how the odds shake out. ing director Natalie DiBerardinis stated in the press release. The Foal That Changed the Warmblood World illtop Farm’s decision to test its breeding stallions for warmblood fragile-foal syndrome (WFFS)— Hwhich kicked off the publicizing of the disor- der—resulted from a tragic loss experienced by one of its clients. In February 2018, Mary Nuttall, co-owner of Southernwood Farm in Conroe, Texas, had to euthanize a WFFS foal born to one of her seasoned and success- ful broodmares, the Westfalen Dorothee (De Kooning – Alabaster, Cor de la Bryere). The attending veterinarians, who had never seen the colt’s horrific symptoms of frag- HEARTBREAKING: This colt, bred by Mary Nuttall, was born with ile, tearing skin and joints so lax he could not stand, fran- WFFS and had to be euthanized just 36 hours after birth tically began researching and eventually recommended that Nuttall have the foal tested for WFFS. When the test came back positive, Nuttall contacted Hilltop, which is the US semen broker for the sport-horse stallions of Van Olst Horses in the Netherlands.

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