WFFS (Warmblood Fragile Foal Syndrome)

WFFS or Warmblood Fragile Foal Syndrome is an inherited disorder of connective tissue that affects the Warmblood and other relative breeds. The disorder displays a relatively wide range of clinical features that correspond to the symptoms of Ehlers-Danlos syndrome in humans. Similar diseases have been already described in dogs, cats, rabbits, minks, sheep and cattle for tens of years and that as a result of various types of mutations with different mode of inheritance.

In the Warmbloods the syndrome is caused by a single mutation (c.2032G> A, p.Gly678Arg) in PLOD1 gene. The PLOD1 encodes the enzyme called lysyl hydroxylase 1 that converts an amino acid called lysine to hydroxylysine. Hydroxylysine is essential for correct function and strength of collagen fibres.

The result of mutation is an extremely thin and fragile to tearing skin that is only loosely attached to subcutaneous tissue.  Due to this mutation the skin is tearing and develops lacerations, seromas, heamatomas, ulcers and scars. Frequent skin lesions occur on legs, head and abdomen.  Besides the skin, lesions can also be found on gums und buccal membrane, the joints of the extremities are lax and hyperextensible.

From the histology point of view, markedly reduced amount of dermal collagen bundles, with changed thickness and spatial orientation of the bundles and abnormally large spaces between dermal fibres can be observed.

The WFFS is incurable. The affected foal dies in prenatal stadium or is born with numerous skin injuries. The infection spreads rapidly in the skin lesions and the health condition of the foal worsens and the foal suffers from pain. The affected foal dies within several days or is euthanatized.

Mutation that causes WFFS is inherited as an autosomal recessive trait. That means the disease affects horses with P/P (positive / positive) genotype only. The horses with P/N (positive /negative) genotype are clinically without any symptom. They are genetically considered carriers of the disease (heterozygotes). In offspring of two heterozygous animals following genotype distribution can be expected: 25 % N/N (healthy non-carriers), 25 % P/P (affected), and 50 % N/P (healthy carriers). Because of high risk of producing affected offspring, mating of two N/P animals (carriers) can not be recommended.

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Reference:

Monthoux, C., de Brot, S., Jackson, M., Bleul, U., Walter, J.: Skin malformations in a neonatal foal tested homozygous positive for Warmblood Fragile Foal Syndrome. BMC Vet Res 11:12, 2015