Fragile foal syndrome, FFS

(Kyphoscoliotic Ehlers-Danlos syndrome)

 

Gene: PLOD1

Transmission: Autosomal recessive

For an autosomal recessive genetic disease an animal must have two copies of the mutation in question to be at risk of developing the disease.  Both parents of an affected animal must be carriers of at least one copy of the mutation.  Animals that have only one copy of the mutation are not at risk of developing the disease but are carrier animals that can pass the mutation on to future generations.

Mutation: Substitution, PLOD1 gene; c.2032 G>A, p.(G678R), exon20

Medical systems: Skeletal, dermal

Breeds: Warmblood breeds, Thoroughbred, Quarter Horse, Standardbred, Morgan

Age of onset of symptoms: At birth

Warmblood Fragile Foal Syndrome (WBFFS) is a hereditary disease seen predominantly in Warmblood breeds involving defective connective tissue synthesis due to a mutation in an enzyme involved in collagen synthesis.  Affected foals are stillborn or die (or are euthanized) shortly after birth due to evident defects.  The skin and mucus membranes are thin, rip easily and the joints are hyperextendable.  WBFFS is seen predominantly in Warmblood breeds but the mutation has also been detected in other breeds. WBFFS has a similar clinical presentation to the genetic disease HERDA, seen in the Quarter Horse, which is caused by a mutation in a different gene.  WBFFS is equivalent to the human disease Ehlers Danlos Syndrome type VI.

 

References:

OMIA link: [1982-9796]

Ablondi M, Johnsson M, Eriksson S, et al. (2022) Performance of Swedish Warmblood fragile foal syndrome carriers and breeding prospects. Genet Sel Evol 54:4. [pubmed/35062868]

Elcombe ME, Bellone RR, Magdesian KG, Finno CJ.  (2022) Prevalence of the RAPGEF5 c.2624C>A and PLOD1 c.2032G>A variants associated with equine familial isolated hypoparathyroidism and fragile foal syndrome in the US Thoroughbred population (1988-2019). Equine Vet J 55(4):666-671.  [pubmed/36199159]

Grillos AS, Roach JM, de Mestre AM, et al. (2021) First reported case of fragile foal syndrome type 1 in the Thoroughbred caused by PLOD1 c.2032G>A. Equine Vet J. [pubmed/34939209]

Roberts JH, Halper J. (2021) Connective tissue disorders in domestic animals. Adv Exp Med Biol 1348:325-335. [pubmed/34807427]

Rowe Á, Flanagan S, Barry G, et al. (2021) Warmblood fragile foal syndrome causative single nucleotide polymorphism frequency in horses in Ireland. Ir Vet J 74:27. [pubmed/34663462]

Martin K, Brooks S, Vierra M, et al. (2020) Fragile Foal Syndrome (PLOD1 c.2032G>A) occurs across diverse horse populations. Anim Genet 52:137-8. [pubmed/ 33165934]

Reiter S, Wallner B, Brem G, 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. [pubmed/33353040]

Dias NM, de Andrade DGA, Teixeira-Neto AR, et al. (2019) Warmblood Fragile Foal Syndrome causative single nucleotide polymorphism frequency in Warmblood horses in Brazil. Vet J. 248:101-102. [pubmed/31113555]

Monthoux C, de Brot S, Jackson M, et al. (2015) Skin malformations in a neonatal foal tested homozygous positive for Warmblood Fragile Foal Syndrome. BMC Vet Res. 11:12.[pubmed/25637337]