This is an ever-developing story and will be updated as we gain more information.

Dwarfism in horses can stem from genetics resulting in abnormal growth. Pathology can include a disproportionately small body type, larger head, short limbs and an overall reduction in size; possibly with health, functionality and mobility issues. While dwarfism in horses is most commonly associated with miniature horses and Shetland ponies, it is seen in other breeds as well.

To date, a handful of genetic variants have been identified that are found in studies to either directly cause dwarfism or are closely correlated with dwarfism in the horse. Still, scientists recognize that many genetic variants and factors remain undiscovered, as there continue to be documented cases of dwarf foals born to parents who both test negative for all currently known dwarfism variants. Currently known genetic causes are largely due to mutations in the aggrecan (ACAN) gene while another form of dwarfism has been identified in Friesian horses caused by a mutation in the B4GALT7 gene. Other examples of causes for dwarfism are skeletal atavism (SHOX) and some types of osteochondrodysplasia which are not a result of the ACAN mutations. The count, at present, includes approximately 6 to 7 identified or suspected variants in the horse. By comparison, human dwarfism results from hundreds of genetic variants, so we still have a ways to go in our depth of understanding.

Ongoing research provides a deeper understanding of known genetic variants, allowing for more precise testing and informed breeding and health care decisions. Although the previously mentioned mutations on ACAN and B4GALT7 are not newly discovered variants, they do offer refinements in our knowledge of the equine genome and help us identify other suspect regions.

At Etalon, we are dedicated to ongoing research and thorough due diligence, ensuring we share the most recent and accurate information with our community. In the case of Fragile Foal Syndrome (FFS), for example—a variant discovered in 2013—we were the first to identify and publish its presence in breeds beyond the previously believed “Warmblood” group. We are committed to providing widespread access to testing and continue advancing equine genetic knowledge for horse owners, breeders, and veterinarians.

The Role of the ACAN Gene in Dwarfism

The ACAN genetic region is responsible for producing aggrecan, a crucial component of cartilage that supports proper bone development. Variations (mutations) in this gene disrupt normal growth, leading to dwarfism in horses. Researchers have identified several specific ACAN mutations, commonly labeled D1, D2, D3 and D4, that contribute to dwarfism when inherited in certain combinations.

Key Genetic Combinations and Their Effects

D1-4/D1-4 (Homozygous for Dwarfism) – The foal expresses severe dwarfism traits, or possibly incompatible with life.

D1-4/n (Heterozygous for Dwarfism) – The horse is a carrier and does not exhibit dwarf characteristics but it is possible that they may be slightly smaller than other siblings.*

n/n (No Variant Detected) – The horse is genetically clear of these mutations.

Horses inheriting two dwarfism variants (such as D2/D2, D2/D3, etc) typically exhibit dwarf characteristics, while homozygous specifically including “D1”, such as “D1/D4” cases are often lethal.

*There have been some studies indicating that the presence of one variant (i.e. D1/n) that the horse may have slightly reduced body size when compared to like-bred horses.

New Discoveries in ACAN Research

The "Brazilian Variant (ACAN_D5bR)" Mystery

A variant initially identified in Brazilian Miniature horses, formerly labeled ACAN_D5, was believed to be associated with dwarfism. However, further research indicated that this variant does not directly cause dwarfism but is correlated with dwarfism. This means it may be linked to another, still-unknown, mutation in miniature horses. Due to this uncertainty, this variant is not classified as a confirmed “cause” of dwarfism but as an associated variant and therefore classified as a “risk” variant.

*** The Newly Identified ACAN_D5kyR Mutation

A recent 2023 PhD study by Dr. John Eberth uncovered another novel ACAN mutation in American Miniature horses, now labeled ACAN_D5kyR. This mutation helps explain previous mystery cases where horses exhibited dwarfism despite not carrying the known D1-D4 mutation combinations. The discovery of ACAN_D5kyR may enhance the accuracy of genetic testing and provide breeders with better insight into potential dwarfism risks. This newly discovered variant is, again, an associated variant, not causative, and therefore classified as a risk variant.

Dwarfism in Friesian Horses: The B4GALT7 Gene Mutation

Dwarfism in Friesian horses can be caused by a mutation in the B4GALT7 gene, specifically the ECA14:g.4535550C > T variant. Unlike ACAN-related dwarfism, which is primarily shown in miniature horses and Shetland ponies, B4GALT7 mutation causes a distinct form of dwarfism characterized by disproportionate growth, affecting the limbs and ribs while leaving the head size relatively normal.

Key Genetic Combinations and Their Effects

dfr/dfr (Homozygous for Dwarfism) – The foal expresses severe dwarfism traits, with abnormally short legs and a disproportionate back.

dfr/n (Heterozygous for Dwarfism) – The horse is a carrier but does not exhibit dwarf characteristics.

n/n (No Variant Detected) – The horse is genetically clear of this mutation.

Research indicates that Friesian dwarfism is inherited in an autosomal recessive manner, meaning that only horses inheriting two copies of the mutation will be affected. Heterozygous horses (dfr/n) are carriers but do not exhibit dwarfism traits.

Implications for Breeders and Horse Owners

With the latest advancements in genetic testing, breeders can make more informed decisions to minimize the risk of producing affected foals.

Key Takeaways:

ACAN mutations D1-D4 are confirmed causative variants for dwarfism in miniature horses and Shetland ponies when inherited in specific combinations.

The previously reported "Brazilian Variant" (ACAN_D5bR) is not currently shown as a causative mutation in Shetland ponies and miniature horses and is only reported as a Risk variant.

The newly discovered ACAN_D5kyR mutation in Shetland ponies and miniature horses clarifies some previously unexplained dwarfism cases. It is not confirmed as a causative mutation and is being reported as a Risk variant.

Both ACAN_D5bR (the Brazilian variant) and ACAN_D5kyR (the Kentucky variant) are seen in many breeds of horses. Published studies have documented homozygous positive horses (D5bR/D5bR) in adult, non-miniature horses who are not dwarves.

B4GALT7 mutations cause dwarfism in Friesian horses, affecting limb and rib growth. Genetic testing for ACAN and B4GALT7 mutations is crucial for responsible breeding practices and ensuring the health of affected horse populations.

Have you encountered dwarfism in your herd?

We’re inviting horse owners and breeders to take part in an important research study. Your insights and experiences are valuable to our understanding of equine dwarfism.

If you're interested in contributing, please reach out to our team. To support the research, be prepared to share horse photos, genetic testing history, and relevant health records.

Together, we can deepen our knowledge and make a difference.

About Etalon Equine Genetics

As genetic research continues to evolve, it is essential for breeders and horse owners to stay informed about the latest discoveries. Etalon Equine Genetics remains committed to providing the most up-to-date and scientifically validated genetic testing services to support responsible breeding and equine health management.

For more information on ACAN and B4GALT7 testing or to discuss your horse’s genetic profile, please contact Etalon Equine Genetics.

References

ACAN:

Etalon Equine Genetics Eberth, J.E., "MOLECULAR GENETIC STUDIES OF HORSES, ESPECIALLY WITH REFERENCE TO AGGRECAN AND DWARFISM" (2023). Theses and Dissertations--Veterinary Science. 59. https://doi.org/10.13023/etd.2023.276

Graves K.T., Eberth J.E. & Bailey E. (2020). Heterozygotes for ACAN dwarfism alleles in horses have reduced stature. Animal Genetics, 51, 420–422. https://pubmed.ncbi.nlm.nih.gov/32065671/ de Andrade, D.G.A., Basso, R.M., Magro, A.J. et al. Evaluation of a new variant in the aggrecan gene potentially associated with chondrodysplastic dwarfism in Miniature horses. Sci Rep 10, 15238 (2020). https://doi.org/10.1038/s41598-020-72192-3

B4GALT7:

Leegwater, P.A., Vos-Loohuis, M., Ducro, B.J. et al. Dwarfism with joint laxity in Friesian horses is associated with a splice site mutation in B4GALT7 . BMC Genomics 17, 839 (2016). https://doi.org/10.1186/s12864-016-3186-0