OMIA:001163-9796 : Myeloencephalopathy, degenerative in Equus caballus (horse)

Categories: Nervous system phene

Mendelian trait/disorder: unknown

Considered a defect: yes

Species-specific name: Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy

Species-specific symbol: eNAD/EDM

Species-specific description: In a detailed review, Finno and Johnson (2022) stated "it was apparent that eNAD [equine NeuroAxonal Dystrophy; OMIA:000715-9796 : Neuroaxonal dystrophy, generic in Equus caballus] was clinically indistinguishable from EDM [Equine Degenerative Myeloencephalopathy; this OMIA entry], and the current consensus is that the conditions have such striking clinical and pathologic similarities that eNAD could be considered a localized form of EDM or EDM a more diffuse form of eNAD."

Inheritance: Posbergh et al. (2018): "The ABD [autozygosity by difference] score difference pattern suggests an autosomal recessive pattern of inheritance [in the Caspian breed] . . . [but] . . . the recessive inheritance pattern seen here contrasts with other studies of EDM in other breeds".

Mapping: Using the novel Autozygosity-by-Difference (ADB) method, Posbergh et al. (2018) mapped this disorder in the Caspian breed to ECA3:71,381,589-73,566,775 (equCab2), which contains just one gene, namely ADGRL3, encoding adhesion G protein-coupled receptor L3. Leeb (2109) questioned this mapping result, partly on the basis that the controls were not breed-matched with the cases. From Posberg et al. (2018), it appears that the 90 controls comprised almost all of a panel of 96 horses made up of 48 Thoroughbreds and 3 each of 16 other breeds, including 3 Caspians. In responding, Posbergh et al. (2019) defended their mapping result, but admitted that "Using a variety of controls reduces the chances of this correction [the breed correction that is key to the use of controls in the ADB method] taking place".

Molecular basis: Posbergh et al. (2018) reported a positional candidate missense SNP in the ADGRL3 gene at ECA3:71770084; c.?A>G; p.Asn?Ser. Noting that the only two surviving homozygotes for this variant within this breed do not show any clinical signs, Posbergh et al. (2018) cautiously described the variant as "a genetic risk factor, working in conjunction with environmental factors, in the development of the EDM in the Caspian breed". Responding to doubts raised by Leeb (2019), Posbergh et al. (2019) concluded that "We do not assert that the investigated change [i.e. the above variant] is causative of equine degenerative myeloencephalopathy (EDM) disease." This conclusion was reinforced by Marquardt et al. (2019) who, having investigated the above variant and related variants in "31 postmortem-confirmed eNAD [Equine neuroaxonal dystrophy]/EDM cases and 43 clinically phenotyped controls from various breeds", concluded that "the four SNPs, including the missense variant in the ADGRL3 region, are not associated with risk for eNAD/EDM across multiple breeds of horses".

Clinical features: Marquardt et al. (2019): "Equine neuroaxonal dystrophy/equine degenerative myeloencephalopathy (eNAD/EDM) is a neurologic disease that has been reported in young horses from a wide range of breeds. Equine degenerative myeloencephalopathy (EDM) is a more histologically advanced form of equine neuroaxonal dystrophy (eNAD)."

Breed: Caspian (Horse) (VBO_0000930).
Breeds in which the phene has been documented. (If a likely causal variant has been documented for the phene, see the variant table breeds in which the variant has been reported).

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2024). OMIA:001163-9796: Online Mendelian Inheritance in Animals (OMIA) [dataset].


Note: the references are listed in reverse chronological order (from the most recent year to the earliest year), and alphabetically by first author within a year.

2023 Ma, Y., Peng, S., Donnelly, C.G., Ghosh, S., Miller, A.D., Woolard, K., Finno, C.J. :
Genetic polymorphisms in vitamin E transport genes as determinants for risk of equine neuroaxonal dystrophy. J Vet Intern Med , 2023. Pubmed reference: 37937700. DOI: 10.1111/jvim.16924.
2022 Finno, C.J., Johnson, A.L. :
Equine neuroaxonal dystrophy and degenerative myeloencephalopathy. Vet Clin North Am Equine Pract 38:213-224, 2022. Pubmed reference: 35811203. DOI: 10.1016/j.cveq.2022.04.003.
2020 Hales, E.N., Esparza, C., Peng, S., Dahlgren, A.R., Peterson, J.M., Miller, A.D., Finno, C.J. :
Genome-wide association study and subsequent exclusion of ATCAY as a candidate gene involved in equine neuroaxonal dystrophy using two animal models. Genes (Basel) 11, 2020. Pubmed reference: 31936863. DOI: 10.3390/genes11010082.
2019 Leeb, T. :
Concern regarding the publication by Posbergh et al. "A nonsynonymous change in adhesion G protein-coupled receptor L3 associated with risk for equine degenerative myeloencephalopathy in the Caspian horse," J Equine Vet Sci 2018;70:96-100. J Equine Vet Sci 72:124, 2019. Pubmed reference: 30929777. DOI: 10.1016/j.jevs.2018.10.021.
Marquardt, S.A., Wilcox, C.V., Burns, E.N., Peterson, J.A., Finno, C.J. :
Previously identified genetic variants in ADGRL3 are not associated with risk for equine degenerative myeloencephalopathy across breeds. Genes (Basel) 10, 2019. Pubmed reference: 31491999. DOI: 10.3390/genes10090681.
Posbergh, C.J., Pollott, G.E., Southard, T.L., Divers, T.J., Brooks, S.A. :
Response to: "Concern Regarding the Publication by Posbergh et al". J Equine Vet Sci 72:124-125, 2019. Pubmed reference: 30929776. DOI: 10.1016/j.jevs.2018.10.022.
2018 Posbergh, C.J., Pollott, G.E., Southard, T.L., Divers, T.J., Brooks, S.A. :
A nonsynonymous change in adhesion G protein–coupled receptor L3 associated with risk for equine degenerative myeloencephalopathy in the Caspian horse. Journal of Equine Veterinary Science 70:96-100, 2018. DOI: 10.1016/j.jevs.2018.08.010.
2017 Finno, C.J., Kaese, H.J., Miller, A.D., Gianino, G., Divers, T., Valberg, S.J. :
Pigment retinopathy in warmblood horses with equine degenerative myeloencephalopathy and equine motor neuron disease. Vet Ophthalmol 20:304-309, 2017. Pubmed reference: 27491953. DOI: 10.1111/vop.12417.
2011 Finno, C.J., Higgins, R.J., Aleman, M., Ofri, R., Hollingsworth, S.R., Bannasch, D.L., Reilly, C.M., Madigan, J.E. :
Equine degenerative myeloencephalopathy in Lusitano horses. J Vet Intern Med 25:1439-46, 2011. Pubmed reference: 22092640. DOI: 10.1111/j.1939-1676.2011.00817.x.
1997 Miller, M.M., Collatos, C. :
Equine degenerative myeloencephalopathy Veterinary Clinics of North America - Equine Practice 13:43 ff., 1997.
1996 Picavet, M.T., Debaerdemaeker, P., Sustronck, B., Boussauw, B., Wilderjans, H. :
Equine degenerative myeloencephalopathy Vlaams Diergeneeskundig Tijdschrift 65:144-147, 1996.
1992 Blythe, L.L., Craig, A.M. :
Equine Degenerative Myeloencephalopathy .2. Diagnosis and Treatment Compendium on Continuing Education for the Practicing Veterinarian 14:1633-1636, 1992.
1991 Blythe, L.L., Hultgren, B.D., Craig, A.M., Appell, L.H., Lassen, E.D., Mattson, D.E., Duffield, D. :
Clinical, viral, and genetic evaluation of equine degenerative myeloencephalopathy in a family of Appaloosas. J Am Vet Med Assoc 198:1005-13, 1991. Pubmed reference: 2032902.
1990 Dill, S.G., Correa, M.T., Erb, H.N., deLahunta, A., Kallfelz, F.A., Waldron, C. :
Factors associated with the development of equine degenerative myeloencephalopathy. Am J Vet Res 51:1300-5, 1990. Pubmed reference: 2386332.
1988 Hultgren, B.D., Appell, L.H., Wagner, P.C., Blythe, L.L., Watrous, B.J., Slizeski, M.L., Duffield, D.A., Goldie, P., Clarkson, D., Shell, D. :
Current research topics in Equine Genetics, Part 2 Equine Practice 10:19-22, 1988.

Edit History

  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Frank Nicholas on 27 Sep 2018
  • Changed by Frank Nicholas on 04 Apr 2019
  • Changed by Frank Nicholas on 10 Sep 2019
  • Changed by Frank Nicholas on 12 Jul 2022
  • Changed by Imke Tammen2 on 10 Nov 2023
  • Changed by Imke Tammen2 on 15 Apr 2024