Renal Cystadenocarcinoma and Nodular Dermatofibrosis (RCND)

 

Gene: FLCN

Transmission: Autosomal dominant

For an autosomal dominant genetic disease, an animal must have at least one copy of the mutation in question to be at risk of developing the disease.  Animals with two copies of the mutation generally have more severe symptoms and an earlier onset of the disease than animals with just one copy of the mutation.  One or both of the parents of an animal with the mutation has one or two copies of the mutation.  Animals that have one or two copies of the mutation can pass the mutation on to future generations.

Mutation: Substitution, FLCN gene; c.764 A>G, p(H255R)

Medical system: Renal, dermal

Breeds: German Shepherd

Age of onset of symptoms: Around the age of 5 years for skin lesions, by 8 years for renal tumors.

First clinical signs of this condition appear around the age of 5 years in the form of small, firm, non-painful nodules on the skin of the head and legs.  With time these nodules enlarge and can become ulcerated and painful.  Although asymptomatic renal cysts develop from an early age, by 8 years most affected dogs will have developed renal tumors of the type cystic adenocarcinoma.  Unsterilized females may also develop smooth muscle tumors within the uterus.  Clinical signs associated with the renal tumor include polyuria and polydipsia, loss of appetite and weight, distended abdomen due to ascites fluid accumulation and vomiting.  It is suspected that embryos with two copies of the mutation (M/M) do not survive and are resorbed during gestation.

 

References:
OMIA link: [1335-9615]

Donner J, Freyer J, Davison S, et al. (2023) Genetic prevalence and clinical relevance of canine Mendelian disease variants in over one million dogs.  PLoS Genet. 19(2):e1010651. [pubmed/36848397]

Ciccarelli S, Di Bello A, Valastro C, et al. (2019) Unilateral renal cystadenocarcinoma and nodular dermatofibrosis in a mixed-breed dog carrying a FLCN gene mutation. Vet Dermatol 30(2):174-e54. [pubmed/30672048]

Bønsdorff TB, Jansen JH, Thomassen RF, Lingaas F. (2009) Loss of heterozygosity at the FLCN locus in early renal cystic lesions in dogs with renal cystadenocarcinoma and nodular dermatofibrosis. Mamm Genome 20:315-20.  [pubmed/19387735]

Bønsdorff TB, Jansen JH, Lingaas F. (2008) Second hits in the FLCN gene in a hereditary renal cancer syndrome in dogs. Mamm Genome 19:121-6. [pubmed/18219524]

Lingaas F, Comstock KE, Kirkness EF, et al. (2003). A mutation in the canine BHD gene is associated with hereditary multifocal renal cystadenocarcinoma and nodular dermatofibrosis in the German Shepherd dog. Human Molecular Genetics 12(23):3043-3053. [pubmed/14532326]

Jónasdóttir TJ, Mellersh CS, Moe L, et al. (2000) 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. [pubmed/10759551]