Chondrodysplasia

Chondrodysplasia is a genetic disorder characterized by abnormal cartilage development, resulting in impaired growth. This condition is due to mutations in the UGDH gene, which encodes an enzyme crucial for the synthesis of glycosaminoglycans, major components of cartilage. As a result, cats with chondrodysplasia may have short legs or skeletal abnormalities.

Symptoms

Chondrodysplasia in cats manifests primarily as short stature, with shortening of the forelimbs and hindlimbs compared to unaffected Munchkin cats. Shortening of the distal and proximal long bones, including the humerus, radius, ulna, and metacarpals, with significant reductions in length compared to normal domestic cats is observed. In addition, rotations and structural defects affecting the carpal and elbow joints are also observed.

Disease Management

Management of chondrodysplasia in cats primarily involves measures to improve their quality of life and reduce the discomfort associated with skeletal deformities. This may include adjustments to the environment to facilitate the cat`s mobility. In addition, dietary modifications may be made to maintain a healthy weight and reduce the load on the affected joints.

Genetic basis

This disease follows an autosomal dominant mode of inheritance. Autosomal dominant inheritance means that cats only have to inherit one copy of the mutation or pathogenic variant to be at risk of developing the disease. Each kitten born to a parent carrying one copy of the mutation has a 50% chance of inheriting one copy of the mutation and being at risk for the disease. It is important to note that the homozygous state is lethal in the early embryonic stages. Breeding between cats carrying genetic variants that may cause disease is not recommended, even if they do not show symptoms.

Technical report

Chondrodysplasia is a genetic condition affecting Munchkin cats, characterized by short stature and shortened limbs. In the study by Struck et al. (2020), a mutation in the UGDH (UDP-glucose 6-dehydrogenase) gene was identified on feline chromosome B1. UGDH is a gene involved in the synthesis of heparan sulfate proteoglycans (HSPGs), which play a crucial role in the regulation of growth factors and morphogens, such as fibroblast growth factor (Fgf), among others. The genetic variant responsible consists of a complex deletion of 3303 base pairs together with an insertion of 108 base pairs. This leads to the formation of a truncated and modified UGDH protein, which probably contributes to early embryonic death in homozygous mutant individuals.

Most affected breeds

Munchkin

Bibliography

Struck AK, Braun M, Detering KA, et al. A structural UGDH variant associated with standard Munchkin cats. BMC Genet. 2020 Jun 30