Test Detail

Lethal congenital ciliopathy of the Norwich Terrier that combines diffuse cystic renal dysplasia with congenital portal hepatic fibrosis. Affected puppies are born with dysplastic kidneys and bile plate anomalies, and usually die in the first days of life from renal or respiratory failure. The disease is inherited in an autosomal recessive manner and is associated with a variant in the INPP5E gene, involved in primary ciliary function. It has no curative treatment.

Affected breed: Norwich Terrier. In the published Finnish cohort the carrier frequency was 6% (29/483 dogs), with the variant not detected outside that family and the breed. It is a rare disease, concentrated in lines related to a common ancestor traceable 15 generations back.

- Test breeding animals before mating (INPP5E test available)
- Do not mate two carriers: 25% risk of affected lethal homozygotes
- A carrier can be mated with a clear animal; offspring intended for breeding must be tested
- Prioritise breed genetic diversity when replacing carriers with clear descendants
- Exclude affected animals and their known carrier parents from breeding

Differential diagnosis with other hepatorenal ciliopathies (e.g. renal polycystosis due to PKD1 in the Bull Terrier) and with isolated juvenile renal dysplasias. Liver biopsy shows bile plate malformation with portal fibrosis without biliary stasis. Genetic testing is the diagnostic tool of choice, since the phenotype manifests in newborns and necropsy is usually the first finding.

1. Dillard KJ et al. (2018) A splice site variant in INPP5E causes diffuse cystic renal dysplasia and hepatic fibrosis in dogs. PLoS One 13(9):e0204073. PMID: 30235266
2. OMIA:002173-9615. Diffuse cystic renal dysplasia and hepatic fibrosis in Canis lupus familiaris. https://omia.org/OMIA002173/9615/