Chondrodysplasia, chondrodystrophy and degeneration of intervertebral discs

Extremely shortened legs are a trait that defines many dog breeds. The reduced long bone length occurs as a consequence of abnormal growth of cartilage and early changes in the structure of growth plates and their premature calcification that result in shortened leg bones with bowed appearance. Currently, two conditions causing these short-legged phenotypes (or disproportional dwarfism) are known – chondrodysplasia and chondrodystrophy.

Chondrodysplasia is caused by insertion of retrogene encoding fibroblast growth factor 4 (FGF4) in dog chromosome 18 that is involved in many biological processes incl. bone development. It occurs in breeds such as Basset Hound, Welsh Corgi, Dachshund, West Highland White Terrier and Scottish Terrier. The inheritance of this mutation is considered to follow an autosomal dominant mode. This means that this phenotype is expressed when a dog obtains only one allele from one of its parents.

The mutation causing chondrodystrophy has been discovered recently as a second FG4-retrogene insertion in dog chromosome 12.  This mutation explains a short-legged phenotype in other dog breeds such as Jack Russel Terriers, Dandie Dinmont Terriers, French Bulldogs, Chihuahua, Chinese Crested, Pekingese, Shih Tzu, Havanese, Coton de Tulear, Bishon Frise, Miniature  and Toy Puddle, Beagle, Cavalier King Charles Spaniel, English Springer  Spaniel, American Cocker Spaniel, Portuguese Water Dog, Nova Scotia Duck Tolling Retriever or Chesapeake Bay Retriever. Dogs that carry both mutations show a more drastic reduction of leg length. The affected breeds are in particular Basset Hounds, Dachshund, Welsh Corgi and Scottish terriers.

Beside the reduction of the leg length the insertion in chromosome 12 is also connected with predisposition to abnormal growth and development of intervertebral discs. In affected dogs, premature calcification at early age (from birth to 1 year of age) results in loss of flexibility and gradual degeneration of intervertebral discs. These abnormal discs are predisposed to herniation into the spinal canal where the inflammation and haemorrhage can cause severe pain and neurological dysfunction termed Intervertebral Disc Disease of type I (IVDD).  IVDD has high mortality rate and high cost of surgical and medical veterinary care.

To the breeds at high risk for IVDD belong Dachshunds, Welsh Corgi, Pekingese, Shih Tzu, Cocker Spaniel, French Bulldog and Beagle.

The mutation for chondrodystrophy is inherited as a semi-dominant trait for height, meaning that dogs with 2 copies of the mutation are smaller than dogs with only 1 copy. As to predisposition to degeneration of intervertebral discs, the inheritance follows an autosomal dominant mode meaning that 1 allele obtained from one of its parents is sufficient to expressing the phenotype.

Genetic testing for these mutations can help breeders determine if CDDY is present among breeding stock and to identify dogs at risk for IVDD. In breeds where both mutations are present, breeders can benefit from test results to implement breeding strategies to reduce  incidence of CDDY, while retaining the short-legged phenotype conferred by CDPA.

The list of breeds for which the IVDD examination is appropriate will be further expanded.

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Reference:

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