Skin malformations in a neonatal foal tested homozygous positive for Warmblood Fragile Foal Syndrome

BACKGROUND: Skin malformations that resembled manifestations of Ehlers-Danlos-Syndrome were described in a variety of domestic animals during the last century as cutis hyperelastica, hyperelastosis cutis, dermatosparaxis, dermal/collagen dysplasia, dermal/cutaneous asthenia or Ehlers-Danlos-like syndrome/s. In 2007, the mutation responsible for Hereditary Equine Regional Dermal Asthenia (HERDA) in Quarter Horses was discovered. Several case reports are available for similar malformations in other breeds than Quarter Horses (Draught Horses, Arabians, and Thoroughbreds) including four case reports for Warmblood horses. Since 2013, a genetic test for the Warmblood Fragile Foal Syndrome Type 1 (WFFS), interrogating the causative point mutation in the equine procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1, or lysyl hydroxylase 1) gene, has become available. Only limited data are available on the occurrence rate and clinical characteristics of this newly detected genetic disease in horses. In humans mutations in this gene are associated with Ehlers-Danlos Syndrome Type VI (kyphoscoliotic form). CASE PRESENTATION: This is the first report describing the clinical and histopathological findings in a foal confirmed to be homozygous positive for WFFS. The Warmblood filly was born with very thin, friable skin, skin lesions on the legs and the head, and an open abdomen. These abnormalities required euthanasia just after delivery. Histologic examination revealed abnormally thin dermis, markedly reduced amounts of dermal collagen bundles, with loosely orientation and abnormally large spaces between deep dermal fibers. CONCLUSION: WFFS is a novel genetic disease in horses and should be considered in cases of abortion, stillbirth, skin lesions and malformations of the skin in neonatal foals. Genetic testing of suspicious cases will contribute to evaluate the frequency of occurrence of clinical WFFS cases and its relevance for the horse population.