BHD case reports

Patient case studies are an important part of clinical investigations into any disease. Such studies can lead to the identification of associated symptoms, genotype-phenotype correlations and further understanding regarding the onset and progression of symptoms. The only symptoms currently associated with BHD Syndrome are fibrofolliculomaslung cysts, pneumothoraxrenal cysts and renal tumours. However, several other manifestations have been reported in BHD patients and these are listed here and also discussed in more detail here. The association between BHD Syndrome and these symptoms are unknown.

A recent case study presented by Lindor et al. (2012) identified parotid tumours (salivary gland tumours), and subsequently fibrofolliculomas, in a 45 year old woman who was found to have a FLCN mutation. Parotid tumours have been reported previously in BHD individuals, first by Liu et al. (2000), with other reports by Schmidt et al. (2005), Palmirotta et al. (2008) and Maffe et al. (2011). The parotid tumours identified by Lindor et al. are of note as they were found to be oncocytic, a characteristic commonly seen in BHD kidney tumours.

The link between BHD and colorectal cancer has been debated previously in the literature and it is summarised here. A recent paper by Kashiwada et al. (2012) adds further evidence supporting this possible link by identifying a 60 year old woman with BHD who previously had colon carcinoma caused by familial adenomatous polyposis (FAP). Interestingly the woman had both a FLCN mutation and a mutation in the adenomatous polyposis coli (APC) gene, which is known to cause FAP. The authors suggest that the APC mutation could be the ‘driver mutation’ for colon cancer, but that the addition of the FLCN mutation contributed to its development. Further study is needed to investigate this link.

Finally, two separate case reports published this year identified renal angiomyolipomas in BHD patients (Byrne et al., 2012; Tobino and Seyama, 2012). Renal angiomyolipomas are commonly found in patients with Tuberous Sclerosis Complex (TSC), a syndrome with clinical similarities to BHD. It is not surprising that renal angiomyolipomas are seen in both these disorders, as FLCN and TSC1/2 function in the same molecular pathway (as seen in this diagram).

It is important to remember that only the skin, lung and kidney symptoms are currently associated with BHD Syndrome. Further investigation is required to understand the connection, if any, between BHD and other clinical manifestations.


  • Lindor NM, Kasperbauer J, Lewis JE, & Pittelkow M (2012). Birt-Hogg-Dube syndrome presenting as multiple oncocytic parotid tumors. Hereditary cancer in clinical practice, 10 (1) PMID: 23050938
  • Liu V, Kwan T, & Page EH (2000). Parotid oncocytoma in the Birt-Hogg-Dubé syndrome. Journal of the American Academy of Dermatology, 43 (6), 1120-2 PMID: 11100034
  • Schmidt LS, Nickerson ML, Warren MB, Glenn GM, Toro JR, Merino MJ, Turner ML, Choyke PL, Sharma N, Peterson J, Morrison P, Maher ER, Walther MM, Zbar B, & Linehan WM (2005). Germline BHD-mutation spectrum and phenotype analysis of a large cohort of families with Birt-Hogg-Dubé syndrome. American journal of human genetics, 76 (6), 1023-33 PMID: 15852235
  • Palmirotta R, Donati P, Savonarola A, Cota C, Ferroni P, & Guadagni F (2008). Birt-Hogg-Dubé (BHD) syndrome: report of two novel germline mutations in the folliculin (FLCN) gene. European journal of dermatology : EJD, 18 (4), 382-6 PMID: 18573707
  • Maffé A, Toschi B, Circo G, Giachino D, Giglio S, Rizzo A, Carloni A, Poletti V, Tomassetti S, Ginardi C, Ungari S, & Genuardi M (2011). Constitutional FLCN mutations in patients with suspected Birt-Hogg-Dubé syndrome ascertained for non-cutaneous manifestations. Clinical genetics, 79 (4), 345-54 PMID: 20618353
  • Kashiwada T, Shimizu H, Tamura K, Seyama K, Horie Y, & Mizoo A (2012). Birt-Hogg-Dubé syndrome and familial adenomatous polyposis: an association or a coincidence? Internal medicine (Tokyo, Japan), 51 (13), 1789-92 PMID: 22790147
  • Byrne M, Mallipeddi R, Pichert G, & Whittaker S (2012). Birt-Hogg-Dubé syndrome with a renal angiomyolipoma: further evidence of a relationship between Birt-Hogg-Dubé syndrome and tuberous sclerosis complex. The Australasian journal of dermatology, 53 (2), 151-4 PMID: 22571569
  • Tobino K, & Seyama K (2012). Birt-Hogg-Dubé syndrome with renal angiomyolipoma. Internal medicine (Tokyo, Japan), 51 (10), 1279-80 PMID: 22687807

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