A form of disproportionate dwarfism, hereditary and autosomal recessive, described in the Dogo Argentino and the Vizsla. In the Dogo Argentino it is caused by a splice variant in PRKG2 that affects chondrocyte differentiation, with shortening and deformity of the limbs and premature closure of the distal ulnar physis. In the Vizsla (designated SD3) it is associated with a missense variant in PCYT1A, with marked shortening and deformity of the humerus and femur. In both cases affected animals have a relatively normal-sized trunk and short, deformed limbs.

Affected breeds: Dogo Argentino and Vizsla. Carrier frequencies are not reliably published on a large scale; cases are concentrated in consanguineous lines. In the Vizsla, cases have been described in related families and the specific genetic test is available.

- Short, deformed limbs relative to a relatively normal-sized trunk
- In the Dogo Argentino, premature closure of the distal ulnar physis and deformity of the forelimbs
- In the Vizsla, marked shortening of the humerus and femur, with knobbly carpi and curvature of the limbs
- Reduced withers height relative to the standard (in the Vizsla, ~11 cm less than clear dogs)
- Proportionally large head in the Dogo Argentino
- No manifest joint pain described to date, although the long-term course is not fully defined

Disproportionate dwarfism was described in the Dogo Argentino in a consanguineous family with two affected half-siblings; Rudd Garces and colleagues (2021) identified by homozygosity mapping and whole-genome sequencing the variant PRKG2:c.1634+1G>T, which affects the donor splice site and co-segregated perfectly with the phenotype. In the Vizsla, Ludwig-Peisker and colleagues (2022) described a new form, proposed as SD3, associated with the variant PCYT1A:c.673T>C (p.Tyr225His), with perfect co-segregation in a family of six affected dogs; in a study of 131 Vizslas (8 affected and 121 unaffected) the genotype-phenotype association was perfect except for one discordant case attributed to heterogeneity. Dogs homozygous for the variant were on average 11 cm shorter than unaffected ones. Both genes have orthologues implicated in human skeletal dysplasias.

- Test breeding animals with the breed-specific test (PRKG2 in the Dogo Argentino, PCYT1A in the Vizsla)
- Do not mate two carriers: 25% risk of affected homozygotes
- A carrier may be mated with a clear animal; test offspring intended for breeding
- Exclude affected homozygous animals from breeding
- In the Vizsla, watch for possible heterogeneity: a clear result for PCYT1A does not rule out other causes of dwarfism

Differential diagnosis with the desired chondrodysplasia of short-legged breeds (FGF4 retrogene insertion on CFA18, not associated with disease), with osteochondrodysplasia due to SLC13A1 deletion in the Miniature Poodle, with skeletal dysplasia 2 (COL11A2) in the Labrador and with spondylocostal dysostosis in the Miniature Schnauzer. Radiographs guide and the genetic test confirms. In humans, PCYT1A variants cause spondylometaphyseal dysplasia with cone-rod dystrophy; in affected Vizslas no manifest ocular phenotype has been described.

1. Rudd Garces G et al. (2021) PRKG2 splice site variant in Dogo Argentino dogs with disproportionate dwarfism. Genes (Basel) 12:1489. PMID: 34680883
2. Ludwig-Peisker O et al. (2022) PCYT1A missense variant in Vizslas with disproportionate dwarfism. Genes (Basel) 13:2354. PMID: 36553621