Synovial osteochondromatosis, EXT1-related

Gene: EXT1

Transmission: Autosomal, dominant

The animal only has to have one copy of the mutation to be at risk of developing hypertrophic cardiomyopathy.  Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation.  Offspring are potentially at risk of developing the disease if at least one parent carries the mutation.  Alternatively, the disease is caused by a de novo mutation.

Mutation: Duplication (insertion), EXT1 gene; c1468dupC, p.(Leu490Pro frameshift STOP31), exon6, chromosome F2.

Breed: Domestic

Medical system: Skeletal

Age of onset of symptoms: Seen at 1 year of age.

Synovial osteochondromatosis is a disease that is observed quite rarely in domestic cats. It is characterized by the formation of non-inflammatory, non-malignant masses in several bones.  Small bodies composed of cartilage and bone are found within the synovial surface and may become loose bodies in the joint cavities. The most commonly affected joints are the knee and lower back. Clinical manifestations may vary depending on age and disease progression; early detection and appropriate management are important to improve the quality of life of the affected animal.

A viral etiology involving feline leukemia virus (FeLV) is suspected when synovial osteochondromatosis is diagnosed in mature adult cats that are FeLV positive.  However, when the disease occurs in young or virus-negative animals, a genetic etiology may be suspected.

A one-year-old FeLV-negative domestic cat showed clinical signs of osteochondrosis.  DNA studies using a candidate gene approach based on known human and mammalian mutations causing osteochondrosis revealed a potentially causative dominant mutation in the EXT1 gene.  However, this mutation was not found in a mature FeLV-negative cat also diagnosed with osteochondrosis, suggesting the possibility of a multigenic etiology of the genetic disease in cats.

The c1468dupC mutation described in the EXT1 gene, although of academic interest, does not constitute a major clinical concern for practitioners and feline breeders.

References:

OMIA link: [2554-9685]

Gómez Á, Rodríguez-Largo A, Pérez E, et al. (2023) Feline osteochondromatosis in a 12-year-old feline leukaemia virus-negative cat. J Comp Pathol 205:24-26.  [pm/37597496]

Fujii Y, Uno A, Takitani S, et al. (2022) A frameshift variant in the EXT1 gene in a feline leukemia virus-negative cat with osteochondromatosis. Anim Genet 53:696-699.  [pm/35719100]

Contributed by: Lucas Castonguay and Paul Olteanu, Class of 2029, Faculté de médecine vétérinaire, Université de Montréal.  (Translation DWS)