Test Detail

Warmblood Fragile Foal Syndrome (WFFS) is an autosomal recessive genodermatosis caused by a variant in PLOD1. Homozygous foals are born with extremely thin and friable skin, with severe skin tears and even abdominal wall defects, necessitating euthanasia shortly after birth. Heterozygotes are clinically normal.

Reiter et al. (2020), on 4081 horses from 38 breeds, detected the allele in 4.9 % of the animals (21 breeds), mostly Warmblood, with carrier frequencies of up to 17 % in Hanoverian and Danish Warmblood. Carriers also appeared in Thoroughbred (17/716), Haflinger (2/48), American Sport Pony (1/12) and Knabstrupper (3/46); the allele was not detected in most non-Warmblood breeds.

- Very thin and friable skin at birth\n- Skin lesions and tears on the limbs and head\n- Abdominal wall closure defects\n- Fatal prognosis; euthanasia shortly after birth\n- Heterozygotes with no clinical signs

WFFS was described clinically in foals of Warmblood breeds; Monthoux et al. (2015) published the first detailed clinical and histopathological description in a homozygous foal. The causal variant (PLOD1 c.2032G>A, p.Gly678Arg) was initially documented in a patent application and later confirmed and its population distribution studied; Reiter et al. (2020) characterised its frequency in 38 breeds. Genealogical and historical DNA studies ruled out the Arabian origin previously proposed.

- Genotype breeding animals of Warmblood and related breeds before mating\n- Never mate carrier × carrier: 25 % risk of WFFS foals\n- The appearance of a case confirms that both parents are carriers: do not repeat that mating\n- A carrier may be mated to a clear animal; test the offspring intended for breeding\n- Report the results to the breeders' association to update the carrier map

Histology shows an abnormally thin dermis, with a greatly reduced amount of dermal collagen bundles, loose orientation and abnormally large spaces between the deep dermal fibres, in a picture resembling Ehlers-Danlos. The diagnosis is confirmed with the PLOD1 genetic test; there is no treatment and the prognosis is fatal.

1. Monthoux et al. (2015). Skin malformations in a neonatal foal tested homozygous positive for Warmblood Fragile Foal Syndrome. BMC Vet Res 11:12. PMID: 25637337
2. Reiter 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 (Basel) 11:1518. PMID: 33353040
3. OMIA:001982-9796. kyphoscoliotic Ehlers-Danlos syndrome (kEDS), PLOD1-related in Equus caballus (domestic horse).