Hereditary syndrome of the German Shepherd combining bilateral nodular dermatofibrosis with renal cysts and, frequently, bilateral renal cystadenocarcinoma. It is caused by a missense mutation in the FLCN gene (folliculin; formerly called BHD), the homologue of the gene for human Birt-Hogg-Dubé disease. Affected animals develop skin and renal lesions that may compromise renal function; a lethal effect in homozygosity has been described.

Specific to the German Shepherd. The population frequency is low, but the disease is emblematic because of its similarity to human Birt-Hogg-Dubé. No reliable carrier figures are published; limited data.

- Firm, bilateral and symmetrical skin nodules on the face and limbs
- Bilateral renal cysts
- Renal masses (cystadenocarcinoma) that may be bilateral
- Haematuria and abdominal pain in advanced stages
- Deterioration of renal function with polyuria and polydipsia
- Possible dyspnoea if there is pulmonary metastasis

The syndrome was described in the German Shepherd as a familial association of dermal fibrosis and renal neoplasia. Molecular characterisation identified the responsible gene as the canine homologue of BHD, placing the disease as the natural counterpart of human Birt-Hogg-Dubé. This finding allowed the development of a carrier genetic test for the breed.

- Test breeding animals before mating
- Do not use affected animals as breeding stock; if the line is maintained, always mate with clear animals
- Do not mate two carriers or affected animals
- Clinical monitoring of carriers: periodic renal and skin ultrasound
- Communicate the status to buyers

Differential diagnosis with sporadic renal neoplasms, other hereditary skin syndromes and acquired renal cysts. Skin biopsy and abdominal ultrasound are useful in follow-up. The therapeutic approach is surgical and supportive depending on renal extent.

1. Jónasdóttir TJ, Mellersh CS, Klungland H, et al. Genetic mapping of a naturally occurring hereditary renal cancer syndrome in dogs. Proc Natl Acad Sci U S A 2000;97(8):4132-7. PMID: 10759551
2. 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;12(23):3043-53. PMID: 14532326
3. OMIA:001335-9615 (FLCN). https://omia.org/OMIA001335/9615/