OMIA:001214-9615 : Osteochondromatosis, EXT2-related in Canis lupus familiaris (dog)

Categories: Skeleton phene (incl. short stature & teeth)

Links to possible relevant human trait(s) and/or gene(s) in OMIM: 133701 (trait) , 608210 (gene)

Mendelian trait/disorder: yes

Mode of inheritance: Autosomal dominant

Considered a defect: yes

Key variant known: yes

Year key variant first reported: 2018

Species-specific name: also called: multiple osteochondromas, multiple hereditary exostoses, multiple cartilaginous exostoses, diaphyseal aclasis and hereditary deforming chondrodysplasia

Molecular basis: Friedenberg et al. (2018) reported a likely de novo causal variant in American Staffordshire Terriers as "One heterozygous variant (c.969C > A) is predicted to result in a stop codon in exon 5 of the [EXT2] gene. Sanger sequencing identified the identical mutation in all affected offspring. The mutation was absent in the unaffected offspring, both parents, all available grandparents, and 26 healthy unrelated American Staffordshire Terriers." These same authors note that "Because this mutation arose de novo, the identical mutation is unlikely to be the cause of osteochondromatosis in other dogs. However, de novo mutations in EXT2 are common in humans with osteochondromatosis, and by extension, it is possible that dogs with osteochondromatosis could be identified by sequencing the entire EXT2 gene."

Clinical features: Osteochondromatosis is a skeletal developmental disorder that results in exostoses (cartilage capped bone outgrowths) that develop during the growth period (Pacifici, 2017). Depending on the location and size of the exostoses, osteochondromatosis can clinically present asymptotically, or can cause pain, lameness, paresis and paralysis (Czerwik et al. 2019). Clinical signs often occur due to compression of nearby tissues, including nerve root compression (causing pain) or spinal cord compression (causing paralysis) (Friedenberg et al., 2018). [IT thanks DVM student Lilli Wilhelm, who provided the basis of this contribution in April 2022]

Pathology: Whilst the pathophysiology and progression of the condition remains unclear, the disease is associated with abnormal migration of chondrocytes from the epiphyseal growth plates towards the bony cortex (Czerwik et al., 2019). The heterotopic cartilage cells that become ossified causes irregular bone formation on bone surfaces (Doige, 1987). The exostoses mainly occur on tissues that undergo endochondral ossification, including long bones, ribs and spinous processes of vertebrae (Doige, 1987). Growth of osteochondromas ceases at the time of physeal closure, known as skeletal maturity (Mozos et al., 2002). [IT thanks DVM student Lilli Wilhelm, who provided the basis of this contribution in April 2022]

Breed: American Staffordshire Terrier (Dog) (VBO_0200055).
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).

Associated gene:

Symbol Description Species Chr Location OMIA gene details page Other Links
EXT2 exostosin glycosyltransferase 2 Canis lupus familiaris 18 NC_051822.1 (45796802..45647570) EXT2 Homologene, Ensembl , NCBI gene


By default, variants are sorted chronologically by year of publication, to provide a historical perspective. Readers can re-sort on any column by clicking on the column header. Click it again to sort in a descending order. To create a multiple-field sort, hold down Shift while clicking on the second, third etc relevant column headers.

WARNING! Inclusion of a variant in this table does not automatically mean that it should be used for DNA testing. Anyone contemplating the use of any of these variants for DNA testing should examine critically the relevant evidence (especially in breeds other than the breed in which the variant was first described). If it is decided to proceed, the location and orientation of the variant sequence should be checked very carefully.

Since October 2021, OMIA includes a semiautomated lift-over pipeline to facilitate updates of genomic positions to a recent reference genome position. These changes to genomic positions are not always reflected in the ‘acknowledgements’ or ‘verbal description’ fields in this table.

OMIA Variant ID Breed(s) Variant Phenotype Gene Allele Type of Variant Source of Genetic Variant Reference Sequence Chr. g. or m. c. or n. p. Verbal Description EVA ID Year Published PubMed ID(s) Acknowledgements
980 American Staffordshire Terrier (Dog) Osteochondromatosis EXT2 nonsense (stop-gain) Naturally occurring variant CanFam3.1 18 g.45101754G>T c.924C>A p.(Y308*) XM_014121199.2; XP_013976674.1; published as c.969C>A and p.(Y323*); coordinates in the table have been updated to a recent reference genome and / or transcript 2018 29485212

Cite this entry

Nicholas, F. W., Tammen, I., & Sydney Informatics Hub. (2022). OMIA:001214-9615: 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.

2021 Silva, C.I.F., Ecco, R., Pimentel, S.P., Pereira, R.D.O., Carvalho, P.H., Marliere, M.P., Torres, R.C.S., Nepomuceno, A.C. :
Lumbar myelopathy caused by multiple cartilaginous exostoses in a dog. Top Companion Anim Med 44:100529, 2021. Pubmed reference: 33631383. DOI: 10.1016/j.tcam.2021.100529.
2019 Czerwik, A., Olszewska, A., Starzomska, B., Korta, R., Henrich, M., Wrzosek, M., Schmidt, M.J. :
Multiple cartilaginous exostoses in a Swiss Mountain dog causing thoracolumbar compressive myelopathy. Acta Vet Scand 61:32, 2019. Pubmed reference: 31238951. DOI: 10.1186/s13028-019-0467-z.
2018 Friedenberg, S.G., Vansteenkiste, D., Yost, O., Treeful, A.E., Meurs, K.M., Tokarz, D.A., Olby, N.J. :
A de novo mutation in the EXT2 gene associated with osteochondromatosis in a litter of American Staffordshire Terriers. J Vet Intern Med 32:986-992, 2018. Pubmed reference: 29485212. DOI: 10.1111/jvim.15073.
2012 Smith, T.J., Baltzer, W.I., Löhr, C., Stieger-Vanegas, S.M. :
Primary synovial osteochondromatosis of the stifle in an English Mastiff. Vet Comp Orthop Traumatol 25:160-6, 2012. Pubmed reference: 22286965. DOI: 10.3415/VCOT-11-04-0049.
2002 Mozos, E., Novales, M., Ginel, P.J., Pérez, J., Pool, R.R. :
A newly recognized pattern of canine osteochondromatosis. Vet Radiol Ultrasound 43:132-7, 2002. Pubmed reference: 11954808. DOI: 10.1111/j.1740-8261.2002.tb01660.x.
1999 Green, E.M., Adams, W.M., Steinberg, H. :
Malignant transformation of solitary spinal osteochondroma in two mature dogs. Vet Radiol Ultrasound 40:634-7, 1999. Pubmed reference: 10608692. DOI: 10.1111/j.1740-8261.1999.tb00891.x.
1998 Farrett, W.D., Stone, P.A., McGarry, J.J. :
Rare presentation of hereditary multiple exostoses. A case report. J Am Podiatr Med Assoc 88:135-9, 1998. Pubmed reference: 9542355. DOI: 10.7547/87507315-88-3-135.
1996 Caporn, T.M., Read, R.A. :
Osteochondromatosis of the cervical spine causing compressive myelopathy in a dog Journal of Small Animal Practice 37:133-137, 1996. Pubmed reference: 8683956. DOI: 10.1111/j.1748-5827.1996.tb02362.x.
Jacobsen, L.S., Kirberger, R.M. :
Canine multiple cartilaginous exostoses - unusual manifestations and a review of the literature [Review] Journal of the American Animal Hospital Association 32:45-51, 1996. Pubmed reference: 8963735. DOI: 10.5326/15473317-32-1-45.
1993 Ness, M.G. :
Osteochondroma causing progressive posterior paresis in a Lakeland Terrier puppy Veterinary Record 132:608-609, 1993. Pubmed reference: 8337809. DOI: 10.1136/vr.132.24.608.
1983 Alexander, J.W. :
Selected skeletal dysplasias: craniomandibular osteopathy, multiple cartilaginous exostoses, and hypertrophic osteodystrophy. Vet Clin North Am Small Anim Pract 13:55-70, 1983. Pubmed reference: 6346655. DOI: 10.1016/s0195-5616(83)50004-1.
1978 Doige, C,E., Pharr, J.W. :
Chondrosarcoma arising in multiple cartilaginous exostoses in a dog. J Am Anim Hosp Assoc. 14:605–611, 1978.
1975 Prata, R.G., Stoll, S.G., Zaki, F.A. :
Spinal cord compression caused by osteocartilaginous exostoses of the spine in two dogs. J Am Vet Med Assoc 166:371-5, 1975. Pubmed reference: 1116955.
1971 Chester, D.K. :
Multiple cartilaginous exostoses in two generations of dogs. J Am Vet Med Assoc 159:895-7, 1971. Pubmed reference: 5315272.
Owen,L.N., Bostock, D.E. :
Multiple cartilaginous exostoses with develpment of a metastasizing osteosarcoma in a Shetland Sheepdog Journal of Small Animal Practice 12:507-512, 1971. Pubmed reference: 5315155. DOI: 10.1111/j.1748-5827.1971.tb06262.x.
1970 Canciani, B., Buja, G., Betto, A., Schiavinato, M.L., Martini, B., Miorelli, M., Nava, A., Dingwall, J.S., Pass, D.A., Pennock, P.W., Cawley, A.J. :
Case report. Multiple cartilaginous exostoses in a dog. Can Vet J 11:114-9, 1970. Pubmed reference: 5310518.
Gee, B.R., Doige, C.E. :
Multiple cartilaginous exostoses in a litter of dogs. J Am Vet Med Assoc 156:53-9, 1970. Pubmed reference: 5308093.

Edit History

  • Created by Frank Nicholas on 06 Sep 2005
  • Changed by Frank Nicholas on 26 Mar 2018
  • Changed by Imke Tammen2 on 24 May 2022