Chondrodystrophy, CDDY/ Intervertebral Disc Disease, IVDD

(Hansen’s Type 1)

 

Gene: FGF4 retrogene

Transmission: Autosomal dominant for Intervertebral Disc Disease (IVDD), autosomal semi-dominant for Chondrodystrophy (CDDY), or short legs. Note that the genetics of these phenotypes is complex, and although the FGF4 retrogene is known to be implicated, it is not presumed to be the only genetic factor involved.

Mutation: Insertion, FGF4 retrogene; ins.3209 bp, Chr.12 g.33,710,178

Medical system: Skeletal

Breeds: Breeds with short legs and at risk of IVDD include : Akita, Alaskan Klee Kai, American Cocker Spaniel, American Eskimo Dog, American Foxhound, Basset Hound, Beagle, Bloodhound, Cardigan Welsh Corgi, Dachshund Miniature Longhair/Shorthair, Dachshund Miniature Wirehair, Dachshund Standard Longhair/Shorthair, Dachshund Standard Wirehair, English Springer Spaniel, French Bulldog, Kooikerhondje, Kromfohrlander, Lhasa Apso, Nova Scotia Duck Tolling, Pekingese, Pembroke Welsh Corgi, Presa Canario, Shih Tzu.

Age of onset of symptoms: The chondrodystrophy (short legs) phenotype is a congenital feature and often a desired trait for the dog breeds affected. The Intervertebral Disc Disease is variable in onset and penetration, such that fairly young animals can be affected.

Short legs (Chondrodystrophy) is a characteristic of a number of our dog breeds. Chondrodystrophy is caused by a defect in endochondral ossification (bone formation) of long bones during development. In some breeds, the defects in long bone formation are also associated with defects in bone formation within vertebral bodies, which predispose these breeds to Intervertebral Disc Disease (IVDD). IVDD can have both genetic and environmental causes. An FGF4 retrogene on chromosome 12 is associated with both short legs and Intervertebral Disc Disease (IVDD) in dogs, while a separate FGF4 retrogene on chromosome 18 is only associated with short legs. Intervertebral Disc Disease is characterized by prolapsed discs, acute back pain, loss of coordination, weakness, reluctance for voluntary movements, paralysis and myelopathy. For Dachshunds, estimates for the frequencies of IVDD range from 20 to 62% of the population, while mortality rates of affected dogs can be as high as 24%.

 

References:

OMIA link: [0157-9615]

Bianchi CA, Marcellin-Little DJ, Dickinson PJ, et al. (2023) FGF4L2 retrogene copy number is associated with intervertebral disc calcification and vertebral geometry in Nova Scotia Duck Tolling Retrievers. Am J Vet Res 84:1-10.  [pubmed/36662606]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Palus V, Stehlik L, Necas A, et al. (2023) Cervical intervertebral disc disease in 60 Yorkshire terriers. Front Vet Sci 10:1148802.  [pubmed/37252381]

Thatcher H, Targett M, Alcoverro E, et al. (2023) Incidence and clinical characterisation of thoracolumbar intervertebral disc extrusions in Basset Hounds compared with Dachshunds. Vet Rec 19(1):90. [pubmed/37481518]

Bannasch D, Batcher K, Leuthard F, et.al. (2022) The Effects of FGF4 Retrogenes on Canine Morphology. Genes (Basel). 2022 Feb 10;13(2):325. doi: 10.3390/genes13020325. [pubmed/35205370]

Batcher K, Dickinson P, Maciejczyk K, Brzeski K, et al. (2020) Multiple FGF4 retrocopies recently derived within canids.  Genes 11:839.  [pubmed/32717834]

Batcher K, Dickinson P, Giuffrida M, Sturges B, et al. (2019) Phenotypic Effects of FGF4 Retrogenes on Intervertebral Disc Disease in Dogs. Genes (Basel) 10(6). [pubmed/31181696]

Murphy BG, Dickinson P, Marcellin-Little DJ, et al. (2019) Pathologic Features of the Intervertebral Disc in Young Nova Scotia Duck Tolling Retrievers Confirms Chondrodystrophy Degenerative Phenotype Associated With Genotype. Vet Pathol. 56(6):895-902. [pubmed/31526126]

Brown EA, Dickinson PJ, Mansour T, Sturges BK, et al. (2017) FGF4 retrogene on CFA12 is responsible for chondrodystrophy and intervertebral disc disease in dogs. PNAS 114(43):11476-11481. [pubmed/29073074]

Parker HG, VonHoldt BM, Quignon P, Margulies EH, et al. (2009) An expressed Fgf4 retrogene is associated with breed-defining chondrodysplasia in domestic dogs. Science 325(5943):995-998. [pubmed/19608863]