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Chondrodystrophy (Type 1 IVDD)

General

Disease Name
Chondrodystrophy (Type 1 IVDD)
Mutation
On Ch 12; FGF4 retrogene insertion at 33,710,200 Mb
Test Type
Genetic Disease/Disorder
Details
"Chondrodystrophy, characterized by short limbs and intervertebral disc disease (IVDD), is a common phenotype in many of the most popular dog breeds, including the dachshund, beagle, and French bulldog." "[From Brown et. al 2017]"Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and premature degeneration and calcification of intervertebral discs... Histopathological analysis of the bones of puppies from these breeds demonstrated that their short stature is due to defects in endochondral ossification, the process whereby cartilage is replaced with bone, in the developing limb. Hansen described the two different types of canine IVD prolapse as type I and type II. Type I occurs exclusively in chondrodystrophic breeds and is characterized by premature degeneration of all discs in young dogs. In type I disc disease, the calcified nucleus pulposus may undergo an explosive herniation through the annulus fibrous into the vertebral canal, resulting in inflammation and hemorrhage and causing severe pain and neurological dysfunction..." [Brown et. al, 2017] In summary, Chondrodystrophy Type 1 IVDD means that the dog will have short legs and a stiffened spine - the spine of which may go on to degenerate, even in young dogs, causing inflammation, hemorrage, severe pain, and neurological problems.
Details 2
"Chondrodystrophy in dogs is defined by dysplastic, shortened long bones and premature degeneration and calcification of intervertebral discs... Long bone length in dogs is a unique example of multiple disease-causing retrocopies of the same parental gene in a mammalian species... Extensive examination of growth plates has been performed on many of these short-legged dog breeds (dachshund, Pekingese, French bulldog, spaniels, beagle), as these breeds are also prone to intervertebral disc disease (IVDD). Histopathological analysis of the bones of puppies from these breeds demonstrated that their short stature is due to defects in endochondral ossification, the process whereby cartilage is replaced with bone, in the developing limb. The long bone growth plates show disorganization of the proliferative zone and reduction in the depth of the maturation zone. In addition to the long bones, similar but more subtle changes exist in endochondral ossification of the vertebral bodies...In chondrodystrophic dogs, the nucleus pulposus is gradually replaced by chondrocyte-like cells in chondroid metaplasia (or metamorphosis) that occurs between birth and 1 y of age. Recent studies have shown that in advanced stages of degeneration in nonchondrodystrophoid dogs there is also replacement of notochordal cells by chondrocyte-like cells, similar to the changes observed in chondrodystrophoid dogs, although this happens at an older age. Hansen described the two different types of canine IVD prolapse as type I and type II. Type I occurs exclusively in chondrodystrophic breeds and is characterized by premature degeneration of all discs in young dogs. In type I disc disease, the calcified nucleus pulposus may undergo an explosive herniation through the annulus fibrous into the vertebral canal, resulting in inflammation and hemorrhage and causing severe pain and neurological dysfunction..." [Brown et. al, 2017]
Published
2017, Brown, E.A., Dickinson, P.J., Mansour, T., Sturges, B.K., Aguilar, M., Young, A.E., Korff, C., Lind, J., Ettinger, C.L., Varon, S., Pollard, R., Brown, C.T., Raudsepp, T., Bannasch, D.L. : FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs. Proc Natl Acad Sci U S A 114:11476-11481, 2017. Pubmed reference: 29073074. DOI: 10.1073/pnas.1709082114.
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