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Chondrodystrophy and Chondrodysplasia (CDPA/CDDY, IVDD)
| Acronym: | CDPA/CDDY, IVDD |
| Gene: | FGF4 |
| Mutation: | CFA18ins, CFA12ins |
| Inheritance: | Autosomal Dominant |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Chondrodystrophy in dogs is a common trait identified in many dog breeds, characterized by the shortened length of the limbs, which is a result of early changes in the structure of growth plates. The short-legged phenotype is known by two names: chondrodystrophy and chondrodysplasia. Chondrodysplasia is also known as canine dwarfism. Word ”chondro” comes from cartilage, and ”dysplasia” means abnormal growth, while the word ”dystrophy” means degeneration of the tissue, in this case, of the cartilage. Breeds are known for having shorter than normal limbs are: Bulldogs, Corgis, Dachshunds, Bassett Hounds, Pugs, French Bulldogs, Pekinese, Lhasa Apsos, Shih Tzus, Beagles, and many more.
Except for shorter limbs than normal, other skeletal characteristics of chondrodystrophy include a lower jaw that may protrude further than normal, an unusually short upper jaw, and an over under bit with crooked teeth. Named short-legged breeds are also prone to intervertebral disc disease (IVDD), which impacts the health of the affected animal. Based on the histopathological analysis of the short-legged breed puppies, that the short stature is a consequence of the defects in the process where cartilage is replaced with bone in the developing limb, which is known as endochondral ossification. Chondrodysplasia is caused by an FGF4-retrogene insertion in dog chromosome 18. This mutation explains the short-legged phenotype in breeds such as Basset Hound, Pembroke Welsh Corgi, Dachshunds, West Highland White Terriers, and Scottish Terriers. The mutation is inherited in an autosomal dominant pattern.
The chondrodystrophy is caused by a second FGF4 retrogene insertion on chromosome 12. This mutation is held responsible also for intervertebral disc disease (IVDD). Dogs in which this mutation has been identified are 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 in leg length. The affected breeds are in particular Basset Hounds, Dachshund, Welsh Corgi, and Scottish terriers. In breeds where both mutations are present, breeders can benefit from test results to implement breeding strategies to reduce the incidence of CDDY, while retaining the short-legged phenotype conferred by CDPA.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
AFFECTED HETEROZYGOTE |
Tested mutation was detected in animal with „affected heterozygote“ result. Animal tested as affected heterozygote has one wild-type and one mutation allele, it is in heterozygous state. It is likely to develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
**Penetrance of tested mutation, and potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Parker HG, VonHoldt BM, Quignon P, Margulies EH, Shao S, Mosher DS, Spady TC, Elkahloun A, Cargill M, Jones PG, Maslen CL, Acland GM, Sutter NB, Kuroki K, Bustamante CD, Wayne RK, Ostrander EA. 2009. An expressed fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs. Science 325(5943):995-8. doi: 10.1126/science.1173275.
Brown EA, Dickinson PJ, Mansour T, Sturges BK, Aguilar M, Young AE, Korff C, Lind J, Ettinger CL, Varon S, Pollard R, Brown CT, Raudsepp T, & Bannasch DL. (2017) FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs.
PNAS 114 (43) 11476-11481. http://m.pnas.org/content/early/2017/10/09/1709082114.