Chondrodystrophy with Intervertebral Disc Disease (CDDY with IVDD Dog)
One form of shortened legs (disproportionate dwarfism) in dogs is caused by an FGF4 retrogene at a specific site on dog chromosome 12. This mutation has also been identified as a risk factor for intervertebral disc disease (IVDD). In IVDD, degeneration and/or calcification of the intervertebral discs occurs, causing the gelatinous core to press on the spinal cord. This causes pain and paralysis and can damage the nerves. Two types are distinguished: IVDD type 1 and IVDD type 2. This genetic test identifies the risk factor for IVDD type 1.
The disease occurs predominantly, but not exclusively, in certain short-legged dog breeds. The inheritance is incomplete autosomal dominant. In the study in which the mutation was identified, in all studied dogs with a herniated disc, the mutation was found in homozygosity (two copies) or in heterozygosity (one copy).
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CDDY/IVDD type 1
CDDY
Disproportionate dwarfism has multiple causes, including the tested FGF4 retrogene insertion on Chromosome 12. The shortened leg trait is inherited in an autosomal semi-dominant manner. Dogs with one copy have somewhat shortened legs, while those with two copies have significantly shortened legs, often with bowing. This mutation on chromosome 12 is independent from the mutation on chromosome 18 that also causes short legs; however, it is possible for dogs to have both mutations.
IVDD type I
- Degeneration and calcification of all intervertebral discs (intervertebral discs) already occurs in young dogs.
- As a result of the loss of elasticity, the outer fibrous ring surrounding the gelatinous core of an intervertebral disc can tear.
- The rupture causes the contents of the intervertebral disc to explosively spill out and press on the spinal cord.
- Type 1 therefore proceeds acutely with sudden pain and paralysis.
With the currently available data, it is not yet measurable how high the individual animal's risk is for the actual occurrence of IVDD.
IVDD type 2
- In IVDD type 2, the outer fibrous ring of the intervertebral discs loses its strength and the gelatinous core presses the fibrous ring onto the spinal cord.
- This causes pain and paralysis.
- The symptoms develop gradually and increase over time.
- The continuing pressure impairs the blood supply and often leads to permanent damage to the nerves.
- Usually only individual intervertebral discs are affected.
Breeds affected
Breeds in which the mutation segregates with the onset of disc herniation type 1 according to Brown et. al (2017):
- American Cocker Spaniel
- Basset Hound
- Beagle
- Cardigan Welsh Corgi
- Chesapeake Bay Retriever
- Chihuahua
- Coton de Tulear
- English Springer Spaniel
- French Bulldog
- Jack Russell Terrier
- Miniature Schnauzer
- Nova Scotia Duck Tolling Retriever
- Pekingese
- Pembroke Welsh Corgi
- Poodle
- Portuguese Water Dog
- Scottish Terrier
- Shih Tzu
- Dachshund ***
*** a recent publication (Bruun et al, 2020) states that the test is not meaningful in assessing IVDD risk in dachshunds.
Test Information
The test detects the FGF4 retrogene insertion on chromosome 12. Dogs will have shortened legs, but with the data currently available, it is not yet possible to estimate the risk of IVDD in the individual animal.
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Genotype and Lab Report
Inheritance: incomplete autosomal dominant.
→ The dog will have shortened legs (CDDY), the length of which depends on the number of copies of the mutation. The risk of developing IVDD type 1 is increased if one copy (n/IVDD) or both copies of the gene (IVDD/IVDD) are affected by the mutation. Dogs that do not have a copy of the causative mutation (n/n) do not have an increased susceptibility to disc herniation type 1.
Risk
The test investigates whether the dog carries the FGF4 retrogene insertion on chromosome 12. With the data currently available, it is not yet possible to measure the individual animal's risk of actually developing IVDD.
Genotypes:
n/n = genetically normal
The dog does not have shortened legs as caused by the chromosome 12 FGF4 insertion and has no extra predisposition for developing IVDD. It can therefore not pass it on to its offspring.
n/CDDY = shortened legs, increased risk for IVDD
The dog has one copy of the mutation. It has shortened legs and an increased susceptibility to type 1 IVDD. The mutation is passed on to 50% of the offspring.
CDDY/CDDY = short legs, increased risk for IVDD
The dog has short legs and an increased risk of developing IVDD. The mutation is passed on 100% to the offspring.
Recommendations
When breeding with two affected animals (n/CDDY or CDDY/CDDY), there is a probability for each puppy to inherit one or two copies of the mutation (n/CDDY or CDDY/CDDY) and thus an increased risk of developing IVDD. This should be taken into account when planning breeding and animals with symptoms should be excluded.
Literature
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.
Bruun, C.S., Bruun, C., Marx, T., Proschowsky, H.F., Fredholm, M.: Breeding schemes for intervertebral disc disease in dachshunds: Is disc calcification score preferable to genotyping of the FGF4 retrogene insertion on CFA12? Canine Med Genet 7:18, 2020. Pubmed reference: 33292664. DOI: 10.1186/s40575-020-00096-6.
Further information is available at: Online Mendelian Inheritance in Animals.