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Renal Cystadenocarcinoma and Nodular Dermatofibrosis (RCND)
| Acronym: | RCND |
| Gene: | FLCN (BHD) |
| Mutation: | c.764A>G |
| Inheritance: | Autosomal dominant |
| Sample type: | CHS (Cheek Swab), WBE (Whole Blood EDTA) |
Genetics and characteristics
Renal Cystadenocarcinoma and Nodular Dermatofibrosis (RCND) is a genetic disorder causing kidney, dermal and uterine cancer in German Shepherd Dog. This canine disease is equivalent to a human disorder called Birt-Hogg-Dube. They share phenotypical similarities, such as firm nodules in the skin and subcutis and kidney tumors, and are suspected to share the same causative gene. However, the difference is that Birt-Hogg-Dube human patients frequently experience pneumothorax (lung collapse) and they do not experience uterine leiomyomas, unlike German Shepherds. Versions of the same causative mutation, except in German Shepherds and humans, have been found in rats, mice, and fruit flies. The terms ”carcinoma” and ”adenocarcinoma” are used for a condition in which cancers are formed in the epithelial tissues of skin and body organs. Adenocarcinoma is a type of cancer that forms in mucus-secreting glands throughout the body. It has an aggressive nature with a persistent tendency for metastasis. Dermatofibroma is a term used for a slowly growing benign skin nodule. Benign tumors over time may transition to malignant tumors.
The main complaints in renal Cystadenocarcinoma and Nodular Dermatofibrosis (RCND) affected German Shepherd are tumors and nodules in the skin. Generally, clinical signs can vary greatly between affected dogs, depending on age and the stage of the disease during the examination. Females and males were affected equally. With aging, the number of skin tumors and uterine tumors increased, and the bilateral renal changes became more pronounced. In all examined dogs, nodular dermatofibromas was present, while changes in the kidney region or in the abdomen were present in 60% of the dogs. Excessive thirst and fluid intake (polydipsia), fever, and blood in the urine (haematuria) may be present. Behavioral changes have been recognized, in form of depression and loss of appetite. The first symptoms appear around 6 to 7 years, as small, firm bumps under the surface of the skin. The bumps are most commonly located on the limbs and head. Their range is usually from 2 to mm in diameter. Histopathological examination of kidneys reveals multiple solid and cystic tumors and cysts. Both kidneys are always affected, but they vary in degree. The most frequent metastatic sites were the sternal lymph nodes, liver, lung, renal, and other abdominal lymph nodes, pleura, and peritoneum. Metastasis was also recorded in the spleen and bronchial lymph nodes.
Most of the dogs are euthanized due to the severity of the disorder, while other affected dogs die naturally around 9 years of age. The main causes of natural death are renal cystadenocarcinomas and complications, such as metastasis, together with nodular dermatofibromas and secondary skin infections. Renal Cystadenocarcinoma and Nodular Dermatofibrosis (RCND) in German Shepherd is caused by a mutation in the gene encoding folliculin (FLCN). The gene is mapped to a canine chromosome 5. The function of the protein folliculin, encoded by this gene, is unknown. The disorder is inherited as an autosomal dominant disorder. Homozygous and heterozygous dogs for the mutation will be affected. Homozygous puppies are most likely to die very early in gestation. Since the clinical signs develop in adult age, affected dogs are likely to be already used for breeding. Therefore it is important to be aware of the disorder prior to dog breeding, which is enabled through the performance of Renal Cystadenocarcinoma and Nodular Dermatofibrosis (RCND) DNA test.
Results Reported As
Test Result |
Interpretation of test result |
CLEAR |
Tested mutation was not detected in animal with „clear“ result. Animal tested as clear has wild-type allele in homozygous state (i.e. two pairs of healthy alleles). It will not develop disease caused by tested mutation.* It will pass only wild-type allele to its offspring. |
AFFECTED HETEROZYGOTE |
Tested mutation was detected in animal with „affected heterozygote“ result. Animal tested as affected heterozygote has one wild-type and one mutation allele, it is in heterozygous state. It is likely to develop disease caused by tested mutation.* It can pass wild-type or mutation allele to its offspring. |
AFFECTED |
Tested mutation was detected in animal with „affected“ result. Animal tested as affected has two copies of mutation alleles affecting the gene. It is likely the animal will experience a genetic disorder due to this mutation.** It will pass only mutation allele to its offspring. |
*Test excludes only tested mutation but not possible unknown mutations or factors that can lead to similar condition/symptoms.
**Penetrance of tested mutation, and potential unknown mutations or multiple other factors can possibly affect the likelihood of experiencing a genetic disorder.
References:
Lingaas F, Comstock KE, Kirkness EF, Sørensen A, Aarskaug T, Hitte C, Nickerson ML, Moe L, Schmidt LS, Thomas R, Breen M, Galibert F, Zbar B, Ostrander EA. (2003): 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.
Moe, L., Lium, B. (1997): Hereditary multifocal renal cystadenocarcinomas and nodular dermatofibrosis in 51 German shepherd dogs. Journal of Small Animal Practice (1997) 38.498-505.