Etiology

• Ehlers-Danlos Syndrome (EDS) refers to a group of inherited connective tissue disorders which cause defective collagen synthesis.
• Classical EDS (cEDS) in humans is a rare autosomal dominant disorder predominantly associated with a deficiency of type V collagen (COLLV) encoded by the COL5A1 and COL5A2 genes.
• Various forms of EDS have been identified in many animal species, including cattle.
• Although genetically similar to human Ehlers-Danlos Syndrome, the phenotypic presentation of this condition is sufficiently different in cattle, cf humans, for the cattle condition to be referred to as Ehlers-Danlos-Like syndrome (EDLS).
• EDLS has not been extensively researched in cattle and so much of the published information is extrapolated from human research.
• Human EDS classification distinguishes 13 subtypes and 19 different associated genes mainly involved in collagen and extracellular matrix synthesis and maintenance.
• Human EDS forms are grouped based on the underlying pathogenetic mechanisms related to primary structure and processing of collagen (COL1A1, COL1A2, COL3A1, COL5A1, COL5A2, ADAMTS2), collagen folding and cross-linking (PLOD1, FKBP14), structure and function of the myomatrix (TNXB, COL12A1), glycosaminoglycan biosynthesis (B4GALT7, B3GALT6, CHST14, DSE), complement pathway (C1S, C1R), and intracellular processes (SLC39A13, ZNF469, PRDM5).
• One study has found EDS in cattle to be associated with the COL5A2 gene, which correlates with findings in human patients. However, further research is required.

Predisposing factors

General

• Dam or sire with signs of skin fragility, joint hyperextension, etc.

Pathophysiology

• A genetic abnormality results in an absence in activity of the enzyme procollagen I N-proteinase (pNPI). This results in an accumulation of pre-cursor molecules (pro-collagen) that self-assemble into ribbon-like fibrils, which do not have the normal tensile strength of organized collagen.
• An autosomal recessive mode of inheritance has been identified in Belgian Blue cattle, but further work is required to investigate the modes of inheritance and the genes affected in various cattle breeds.

Epidemiology

• This is a heritable condition and as such consideration should be given as to investigating the sire and dam.
• In-breeding has been associated with EDLS and dermatosparaxis in the Belgian Blue and Charolais breeds.