Chondrodysplasia

Gene: UGDH

Transmission: Autosomal dominant, embryo lethal

The animal with one copy of the mutation will develop the phenotype.  Embryos with two copies of the mutation will die in utero.  Offspring have a 50% risk of having the phenotype if one parent carries the mutation, and a 67% risk of having the phenotype in both parents have the phenotype.

Mutation: Deletion plus insertion, gene UGDH; deletion of 3303 nt, insertion of 108 nt in last 2 exons, chr.B1.

Medical system: Skeletal

Breeds: Munchkin, breeds mated to Munchkins

Age of onset of symptoms: Visible at birth, more pronounced with growth

Munchkin cats have short limbs due to a natural mutation in the UGDH gene that affects long bone formation resulting in disproportionate dwarfism (chondrodystrophy).   The UGDH gene is involved in the synthesis of heparan sulfate proteoglycans (HSGs), which regulate the function of growth factors such as Fibroblast Growth Factor (FGF), Hedgehog (HH), Transforming growth factor-β (TGFβ) that are all important in the endochondral growth of long bones. In the Munchkin cat, there is distal and proximal shortening of the humerus, radius, ulna, metacarpus, femur and tibia, with the anomalies present from birth.  In addition, lordosis and funnel chest (pectus excavatum) may be present. Munchkin cats can be at risk of developing osteoarthritis due to the physical limitations imposed by their short limbs.

It should be noted that the Munchkin cat breed exists in two forms, the “standard” (chondrodystrophic) phenotype with a carrier genotype (M/N) for the UGDH gene mutation, and the “non-standard” (normal) phenotype with a genotype of two normal copies (N/N) of the UGDH gene.  It should also be noted that embryos which are double mutated (M/M, homozygous mutated) for the UGDH gene mutation are not viable and die in utero.  Due to real and potential health problems, the Munchkin cat breed is not recognized by many cat-breeding associations and is banned by law in several countries.

References:

OMIA link: [2541-9685]

Anderson LM, Fox DB, Chesney KL, et al. (2021) Skeletal manifestations of heritable disproportionate dwarfism in cats as determined by radiography and magnetic resonance imaging. Vet Comp Orthop Traumatol 34:327-337.  [pm/34082456]

Buckley RM, Davis BW, Brashear, A, et al. (2020) A new domestic cat genome assembly based on long sequence reads empowers feline genomic medicine and identifies a novel gene for dwarfism. PLoS Genet 16:e1008926.  [pm/33090996]

Struck AK, Braun M, Detering KA, et al. (2020) A structural UGDH variant associated with standard Munchkin cats. BMC Genet 21:67. [pm/32605545]

Contributed by: Sarah Goulet and Siba Moukarzel, Class of 2028, Faculty of Veterinary Medicine, University of Montreal. (Translation DWS).