Warmblood fragile foal syndrome (WFFS) type I is a recessive inherited connective tissue defect characterized by hyperextensible joints and abnormally thin fragile skin and mucous membranes.
Phenotype: Warmblood fragile foal syndrome (WFFS) type I is an inherited connective tissue defect characterized by lax and hyperextensible joints and abnormally thin, fragile skin and mucous membranes causing extensive lesions throughout the body. This is a lethal condition.
Mode of Inheritance: Autosomal recessive
Alleles: N = Normal/Unaffected, WFFS = Warmblood fragile foal syndrome
Breeds appropriate for testing: Various Warmblood breeds, Thoroughbred
Explanation of Results:
Horses with N/N genotype will not have warmblood fragile foal syndrome and cannot pass this warmblood fragile foal syndrome variant to their offspring.
Horses with N/WFFS genotype will not have warmblood fragile foal syndrome, but are carriers. They may transmit this warmblood fragile foal syndrome variant to 50% of their offspring. Matings between two carriers will result in a 25% chance of producing a warmblood fragile foal syndrome-affected foal.
Horses with WFFS/WFFS genotype will have warmblood fragile foal syndrome, a fatal genetic defect of connective tissue.
Warmblood fragile foal syndrome type 1 (WFFS) is a fatal genetic defect of connective tissue characterized by hyperextensible, abnormally thin, fragile skin and mucous membranes (tissue that lines cavities and covers organs) that cause extensive lesions throughout the body. Other signs of the disease include hyperextension of limb articulations, floppy ears, hydrops (accumulation of fluid in fetus), subcutaneous emphysema, hematomas, and premature birth. Signs of the disease are present from birth. Newborn foals are euthanized because of poor prognosis for an untreatable condition.
WFFS is caused by a mutation (c.2032G > A) in the PLOD1 gene (procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1) that codes for an enzyme important for biosynthesis of collagen, which are complex molecules that provide strength and support to many body tissues. The mutation impairs normal function of the enzyme, which leads to development of the disease. In humans, mutations in this gene are associated with a similar defect known as Ehlers-Danlos Syndrome Type VI.
WFFS is inherited as anautosomal recessive defect, which means that both males and females are equally affected and that two copies of the mutation (WFFS/WFFS) are needed to cause the disorder. Horses that carry one copy (N/WFFS) of this recessive mutation are normal but can transmit the mutation to 50% of their offspring.
Testing for WFFS allows clinicians to confirm diagnosis of WFFS. The test benefits breeders and owners to identify carriers of WFFS and to select mating pairs accordingly to avoid producing affected foals. Mating between two carriers has a 25% chance of producing affected foals.
Research at the VGL has identified a low allele and carrier frequency of the WFFS mutation in Thoroughbreds. To date, no Thoroughbreds homozygous for the mutation have been detected. In studying over 700 horses, carrier frequency was 2.4%, meaning out of 200 horses approximately 5 would have one copy of the mutation. Investigating the WFFS allele and carrier frequencies in other breeds is is ongoing. Information about other breeds will be updated when the studies are complete.
Testing recommendation: The test is presently recommended for all Warmblood/Sport Horse populations. The incidence of carriers in Warmblood horses is estimated to be around 9-11%. Additionally, since the WFFS allele has also been detected in the Thoroughbred, albeit at a low frequency, testing could inform mating decisions to avoid breeding carriers.
1 copy of the WFFS mutation. Animal is normal but is a carrier. Horse can pass on the mutation to 50% of offspring.
2 copies of the WFFS mutation. Horse is affected.
Bellone, R., Ocampo, N., Hughes, S., Le, V., Arthur, R., Finno, C., & Penedo, M. (2019). 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. doi: 10.1111/evj.13182
Winand, N. Identification of the causative mutation for inherited connective tissue disorders in equines. United States Department Of Commerce Application Number: 61/486,464; (Filing Date: May 16th, 2011).
Monthoux, C., de Brot, S., Jackson, M., Bleul, U., & Walter, J. (2015). Skin malformations in a neonatal foal tested homozygous positive for Warmblood Fragile Foal Syndrome. BMC Veterinary Research, 11(1), 12. doi: 10.1186/s12917-015-0318-8