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Renal Cystadenocarcinoma and Nodular Dermatofibrosis (FLCN gene)

Renal Cystadenocarcinoma and Nodular Dermatofibrosis (FLCN gene)

Renal cystadenocarcinoma and nodular dermatofibrosis is caused by mutations in the FLCN gene that increase the risk of renal, dermal and uterine cancer.

Symptoms

This pathology is characterized by abnormal masses in the kidneys and skin of dogs, and, in females, it also produces tumors in the uterus. Affected dogs usually present, around 6 years of age, small firm lumps under the surface of the skin of the limbs and head. Tumors also develop in the kidneys between the ages of 9 and 11 years, appearing as nodules that cause chronic kidney disease and can lead to renal failure and metastasis. Signs of chronic kidney disease include frequent urination, blood in the urine, excessive thirst, bloating, poor appetite and weight loss.

Disease Management

There is currently no cure or specific treatment for this disease. Management is focused on relieving symptoms and improving the quality of life of the animal. Skin nodules can be painful and cause discomfort if they are located in areas where they interfere with the dog's normal movement, so treatment may involve surgical removal. Spaying of bitches is usually recommended to reduce the risk of uterine cancer. Veterinary follow-up is performed to assess renal function and supportive treatments are available for the management of renal disease such as special diet and fluid therapy.

Genetic basis

This disease follows an autosomal dominant mode of inheritance. Autosomal dominant inheritance means that dogs only have to inherit one copy of the mutation or pathogenic variant to be at risk of developing the disease. Each puppy 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. Breeding between dogs carrying genetic variants that can cause disease is not recommended, even if they do not show symptoms.

Technical report

Renal cystadenocarcinoma and nodular dermatofibrosis is a rare, naturally occurring, hereditary oncologic syndrome seen in dogs. It is characterized by multifocal tumors in the kidneys and uterus, as well as skin cysts containing dense collagen fibers. It has been shown that this syndrome is caused by mutations that are inherited in an autosomal dominant manner in the FLCN gene. The FLCN gene or folliculin gene, also previously known as BHD, produces a protein that controls cell multiplication and is therefore considered a tumor suppressor gene. Lingaas et al. (2003) identified c.764A>G (FLCN gene) as the disease-causing variant in German shepherd dogs. This variant results in the substitution of an adenine for a guanine in a highly conserved region. The presence of a single copy of the variant is sufficient to increase the risk of developing tumors and puppies with two copies of the variant generally die during development.

Most affected breeds

German Shepherd Dog

Bibliography

Jónasdóttir TJ, Mellersh CS, Moe L,et al. Genetic mapping of a naturally occurring hereditary renal cancer syndrome in dogs. Proc Natl Acad Sci U S A. 2000 Apr 11;97(8):4132-7.

Lingaas F, Comstock KE, Kirkness EF,et al. A mutation in the canine BHD gene is associated with hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis in the German Shepherd dog. Hum Mol Genet. 2003 Dec 1;12(23):3043-53.

Lium B, Moe L. Hereditary multifocal renal cystadenocarcinomas and nodular dermatofibrosis in the German shepherd dog: macroscopic and histopathologic changes. Vet Pathol. 1985 Sep;22(5):447-55.