Fragile Foal Syndrome Type 1 (FFS)

by Amy Young
September 23, 2019

Takeaways

FFS is an autosomal recessive, inherited defect that causes hyperextensible, thin, fragile skin that is subject to open lesions.
The disease is present at birth and affected foals are euthanized due to the severity of the clinical signs.
A mutation in the PLOD1 gene is associated with the disease and a DNA test is available.
The FFS mutation has been reported in warmblood breeds and is at a low frequency in Thoroughbreds.
Eighteen cases of FFS have been reported in warmbloods. One case has been reported in a Thoroughbred. No cases have been reported in other breeds.

What is fragile foal syndrome type 1?

Fragile foal syndrome type 1 (FFS), formerly warmblood fragile foal syndrome (WFFS), is an inherited defect of connective tissue characterized by hyperextensible, abnormally thin, fragile skin and mucous membranes that are subject to open lesions. Affected horses may also have hyperextensible limb joints, floppy ears, accumulation of fluid (hydrops), subcutaneous emphysema, hematomas, and premature birth. The disease is present at birth and affected newborn foals are euthanized shortly after birth due to the poor prognosis of this untreatable condition.

Fragile foal syndrome type 1 is an autosomal recessive disease, meaning that both males and females are equally affected and two copies of the mutation are required to cause the disorder. Horses with one copy do not show clinical signs, but can transmit the mutation to their offspring. A mutation in the PLOD1 (procollagen-lysine, 2-oxoglutarte 5-dioxygenase1) gene has been associated with FFS and a DNA test is available to inform breeding decisions and avoid producing affected foals.

What are the clinical signs of fragile foal syndrome type 1?

The clinical signs of FFS are present from birth and include hyperextensible skin that is abnormally thin and fragile. Friction and pressure points can result in open lesions, often in utero. Affected horses may also exhibit hyperextensible limb joints, floppy ears, hematomas, seromas, hydrops, subcutaneous emphysema, and premature birth. One case report of a confirmed homozygous affected newborn foal described an open abdomen and extensive skin lesions (Monthoux et al. 2015).

How is fragile foal syndrome type 1 diagnosed?

Few cases of FFS have been described, and clinical signs overlap with other diseases such as hereditary regional dermal asthenia (HERDA). As such, necropsy alone is often insufficient for a definitive diagnosis. The available genetic test may be utilized to confirm a diagnosis of FFS.

How is fragile foal syndrome type 1 treated?

Due to the severity of the disease, there is no treatment or “cure” for FFS.

What is the prognosis for fragile foal syndrome type 1?

Affected foals are unfortunately euthanized shortly after birth. The prognosis for carriers is excellent as there are no known health problems associated with carrier status for this disease. It is possible that homozygosity for the PLOD1 mutation results in early embryonic loss, but additional research is needed to explore this hypothesis.

How can fragile foal syndrome type 1 be prevented?

Breeders can prevent FFS in their horses by performing DNA testing on potential sires and dams and avoiding carrier matings. Hair samples (with the roots attached) can be submitted to the UC Davis Veterinary Genetics Laboratory. Offspring of two FFS carriers have a 25% chance of being affected. Breeding an unaffected horse to a carrier will not result in an affected foal but will produce a FFS carrier foal 50% of the time.

The FFS genetic test is currently recommended for all warmblood/sport horse populations and those non-warmblood breeds where the allele has been detected. The carrier frequency of the FFS mutation in warmblood horses is estimated to be 9-11%. A low carrier frequency of the FFS mutation has also been identified in Thoroughbreds (1.2%). Eighteen cases of FFS have been reported in Warmbloods. One case has been reported in a Thoroughbred. No cases have been reported in other breeds. A study of 4,081 horses from 38 different breeds did not detect the FFS allele in most non-warmblood breeds, with the exception of Thoroughbreds, Haflingers, American Sport Ponies, and Knabstruppers.

For more information:

UC Davis Veterinary Genetics Laboratory WFFS Type 1 DNA testing

International collaboration identifies the first case of Fragile Foal Syndrome (FFS) in the Thoroughbred, UC Davis Veterinary Genetics Laboratory

Grillos, A., Roach, J., de Mestre, A., Foote, A., Kinglsey, N., Mienaltowski, M. and Bellone, R. (2022), First reported case of fragile foal syndrome type 1 in the Thoroughbred caused by PLOD1 c.2032G>A. Equine Veterinary Journal. In press.

Metzger, J.; Kreft, O.; Sieme, H.; Martinsson, G.; Reineking, W.; Hewicker-Trautwein, M.; Distl, O. (2020) Hanoverian F/W-line contributes to segregation of Warmblood fragile foal syndrome type 1 variant PLOD1:c.2032G>A in Warmblood horses. Equine Vet. J.:22, 1–9.

Reiter, S., Wallner, B., Brem, G., Haring, E., Hoelzle, L., et al. (2020) Distribution of the Warmblood Fragile Foal Syndrome Type 1 Mutation (PLOD1 c.2032G>A) in Different Horse Breeds from Europe and the United States. Genes 11(12):1518. doi: 10.3390/genes11121518.

Bellone, R., Ocampo, N. , Hughes, S. , Le, V. , Arthur, R. , Finno, C. and 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 52(3):411-414.

Aurich, C.; Müller-Herbst, S.; Reineking, W.; Müller, E.; Wohlsein, P.; Gunreben, B.; Aurich, J. (2019) Characterization of abortion, stillbirth and non-viable foals homozygous for the Warmblood Fragile Foal Syndrome. Anim. Reprod. Sci. 211:106202.

Monthoux C, S Brot, M Jackson, U Bleul, J Walter. (2015) Skin malformations in a neonatal foal tested homozygous positive for Warmblood Fragile Foal Syndrome. BMC Veterinary Research 11:12. doi:10.1186/s12917-015-0318-8.

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). https://patentimages.storage.googleapis.com/df/43/9b/787cf972a3365b/WO2012158711A1.pdf