Test Detail

Two-disease panel with molecular testing aimed at warmblood horses: warmblood fragile foal syndrome (WFFS) and polysaccharide storage myopathy type 1 (PSSM1). WFFS is an autosomal recessive genodermatosis caused by a variant in PLOD1: homozygous foals are born with extremely thin and friable skin, severe skin tears and abdominal wall defects, and are euthanised shortly after birth; heterozygotes are clinically normal. PSSM1 is a dominant muscle glycogenosis with incomplete penetrance caused by GYS1, typical of stock and draft breeds; its presence in the Warmblood population as a whole is not established in the sources consulted (limited data). Each test reports the genotype and makes it possible to plan matings.

Applicable breed: warmblood horses (Warmblood). Panel of 2 diseases.

The signs depend on the condition:\n- WFFS: very thin and friable skin at birth, skin lesions and tears on the limbs and head, abdominal wall closure defects; fatal prognosis and euthanasia shortly after birth. Heterozygotes show no signs.\n- PSSM1: stiffness and muscle pain (tying-up), dark urine and elevated CK/AST, especially after rest and resumption of exercise; it may be limited to poor performance or abnormal gait.

WFFS was described clinically in foals of Warmblood breeds; Monthoux et al. (2015) published the first detailed clinical-pathological description in a homozygous foal. The causal variant (PLOD1 c.2032G>A, p.Gly678Arg) was initially documented in a patent application and was later confirmed and its population distribution studied; Reiter et al. (2020) characterised its frequency in 38 breeds, mostly Warmblood. PSSM1 was defined in the 1990s in Quarter Horses and its mutation in GYS1 (R309H) was identified in 2008; the variant has been described mainly in stock and draft breeds.

Genotype breeding Warmblood and related breeds before mating, with special attention to WFFS.\n- WFFS (recessive): do not mate carrier with carrier (25 % WFFS foals, lethal); the appearance of a case confirms that both parents are carriers and that mating should not be repeated. Carrier with clear produces 50 % carriers and no affected animals; test offspring intended for breeding.\n- PSSM1 (dominant): every carrier transmits the allele to 50 % of the offspring; breed preferably with N/N and avoid carrier × carrier because of the 25 % of more severely affected homozygotes.\n- Report the results to the breeders' association to update the carrier map.

WFFS histology shows an abnormally thin dermis, with sparse dermal collagen bundles and abnormally large spaces between the deep fibres, in an Ehlers-Danlos-like picture. There is no treatment and the prognosis is fatal. As for PSSM1, most of the described cases correspond to stock and draft breeds, and its relevance in the Warmblood population as a whole is uncertain; in the face of a picture of rhabdomyolysis in a Warmblood, PSSM2 and other myopathies should be considered, and the workup completed with a biopsy when indicated. A negative PSSM1 test does not rule out myopathy of another origin.

1. Monthoux C, et al. Skin malformations in a neonatal foal tested homozygous positive for Warmblood Fragile Foal Syndrome. BMC Vet Res. 2015;11:12. PMID: 25637337.
2. Reiter S, et al. 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). 2020;11(12):1518. PMID: 33353040.
3. McCue ME, Valberg SJ, Miller MB, et al. Glycogen synthase (GYS1) mutation causes a novel skeletal muscle glycogenosis. Genomics. 2008. PMID: 18358695.
4. McCue ME, Valberg SJ, Lucio M, Mickelson JR. Glycogen synthase 1 (GYS1) mutation in diverse breeds with polysaccharide storage myopathy. J Vet Intern Med. 2008. PMID: 18691366.