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

Abstract

BackgroundSkin 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 presentationThis 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.ConclusionWFFS 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.

A frameshift variant in the COL5A1 gene in a cat with Ehlers‐Danlos syndrome

“…; Monthoux et al . ). A closely related phenotype is equine regional dermal asthenia (HERDA) in horses, which is caused by a variant in the PPIB gene (Tryon et al .…”

Hereditary equine regional dermal asthenia (HERDA) in Quarter Horses: A review of clinical signs, genetics and research

“…The mutation which causes Warmblood fragile foal syndrome (Monthoux et al . ), which is another form of EDS, has not been reported in Quarter Horses. Junctional epidermolysis bullosa (JEB) (Frame et al .…”

“…Trauma in an unaffected horse could certainly cause wounds similar to those seen with HERDA; however, hyperextensible, loose skin and abnormal scarring are not generally present. The mutation which causes Warmblood fragile foal syndrome (Monthoux et al 2015), which is another form of EDS, has not been reported in Quarter Horses. Junctional epidermolysis bullosa (JEB) (Frame et al 1988;Kohn et al 1989;Lieto et al 2002) could be confused with HERDA but it only occurs in neonatal animals and has not previously been reported in Quarter Horses.…”

Ehlers-Danlos Syndrome in a Mangalarga–Campolina Crossbreed Mare

“…Hereditary Equine Regional Dermal Asthenia is caused by a missense mutation (c.115G>A) in the peptidylprolyl isomerase B (PPIB) gene [4]. Warmblood Fragile Foal Syndrome is also an autosomal recessive disease, but it affects Warmblood breeds [10][11][12][13][14]. The disease is caused by a missense mutation (c.2032G>A) in the equine procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) gene [5].…”

“…The disease is caused by a missense mutation (c.2032G>A) in the equine procollagen-lysine, 2-oxoglutarate 5-dioxygenase 1 (PLOD1) gene [5]. Although the PLOD1 mutation has been identified in only one case report [14], there are four other case reports [10][11][12][13] published before the identification of the causative mutation where the animals were suspected to be affected by the same condition [14].…”