Radiographical Survey of Osteochondrodysplasia in Scottish Fold Cats caused by the TRPV4 gene variant

Hum Genet. 2021 Nov;140(11):1525-1534. doi: 10.1007/s00439-021-02337-5. Epub 2021 Aug 18.


The unique appearance of Scottish Fold cats is caused by a single gene variant in TRPV4, which impacts the development of cartilage. This results in the ears folding forward and variable effects on articular cartilage and bone. While some find this appearance desirable, early work demonstrated that homozygous cats with two copies of this variant develop severe radiographic consequences. Subsequent breeding programs have mated heterozygous cats with straight-eared cats to ensure an equal mix of heterozygous (fold) and wild-type (nonfolded) offspring, in the hope of raising healthy cats. More recent radiological surveys suggest that these heterozygous cats may also have medical problems consisting of deformed distal extremities in the worst cases and accelerated onset of osteoarthritis. However, these previous studies were undermined by selection biases, lack of controls, unblinded assessment and lack of known genotypes. Our aim was to determine if heterozygous cats exhibit radiological abnormalities when controlling for these limitations. Specifically, DNA and radiographs were acquired for 22 Scottish Fold cats. Four reviewers, blinded to the ear phenotype, assessed the lateral radiographs. Genotyping showed that all 10 folded-ear cats were heterozygous, and none of the straight-ear cats (n = 12) had the abnormal TRPV4 variant. Although each reviewer, on average, gave a numerically worse 'severity score' to folded-ear cats relative to straight-ear cats, the images in heterozygous cats showed much milder radiological signs than previously published. This study provides additional information to be considered in the complicated debate as to whether cats with the TRPV4 variant should be bred for folded ears given the potential comorbidities.

MeSH terms

  • Animals
  • Cat Diseases / diagnostic imaging*
  • Cat Diseases / genetics
  • Cats / genetics*
  • Ear, External / anatomy & histology
  • Female
  • Heterozygote
  • Hindlimb / diagnostic imaging
  • Male
  • Osteochondrodysplasias / diagnosis
  • Osteochondrodysplasias / genetics
  • Osteochondrodysplasias / veterinary*
  • Phenotype
  • Radiography
  • TRPV Cation Channels / genetics*


  • TRPV Cation Channels