Genetic basis of Diffuse Cystic Renal Dysplasia and Hepatic Fibrosis in dogs - is caused by a homozygous splice site variant in the INPP5E gene. This gene is linked to ciliary function, and its mutation leads to a ciliopathy affecting kidney and liver development. The disease is inherited in an autosomal recessive manner, meaning a dog must inherit two copies of the mutated gene to show clinical signs. This variant was first identified in Norwich Terriers but has similarities to ciliopathies reported in other breeds.
Pathophysiology - The mutation causes defects in primary cilia, which are essential for normal kidney and liver development during fetal growth. The kidneys develop multiple small fluid-filled cysts, losing the distinction between the renal cortex and medulla (diffuse cystic renal dysplasia). The liver develops fibrosis (scarring), which can impair its function. Additional abnormalities such as cleft palate, diaphragmatic hernia, and underdeveloped lungs are often seen.
Complications - Marked renal cyst formation leading to kidney failure. Liver fibrosis complicates metabolic and detoxification functions. Possible congenital defects such as cleft palate and diaphragmatic abnormalities impacting survival. Most affected puppies show severe symptoms shortly after birth and generally do not survive beyond infancy.
Why This Matters to Breeders and Vets - Puppies affected by this condition usually die shortly after birth due to kidney failure and associated organ dysfunction. Genetic testing allows breeders to avoid mating two carriers, preventing affected offspring. Early diagnosis helps vets and owners make informed decisions about management and humane care