The development of renal cell carcinoma, fibrofolliculomas on the face and trunk and pneumothorax are the widely accepted ‘triad’ of symptoms associated with BHD Syndrome. It’s also important to consider that other clinical manifestations are associated (or at the very least, have been noted to co-occur) with BHD Syndrome in some cases. These include a range of benign and malignant tumours (detailed more fully by Menko et al, 2009*), but perhaps the association between colorectal cancer (CRC) and BHD syndrome is the most debated.
The earliest reports of BHD syndrome often described an association with CRC, but more recent genetic and clinical studies have provided conflicting data which only confuses matters further. A new article by Nahorski et al**, in the Journal of Medical Genetics, addresses this issue, and investigates the role of FLCN in sporadic CRC using combination of clinical and genetic methodologies. Their interesting results suggest that FLCN inactivation might contribute to colorectal tumourigenesis but you’ll have to read the paper yourself to find out the specifics (!). For me, this study represents an extremely informative investigation into an aspect of BHD Syndrome that’s ‘off the beaten trail’, since it doesn’t focus on the classic triad of symptoms previously mentioned, but is no less important, since identifying genotype-phenotype correlations could shed light on potential functional domains of the gene and in general adds to what we know about FLCN function.
Additionally, it’s important to keep in mind that the management and diagnosis of rarer diseases is often lead by current scientific findings (take the Menko* paper for example) and that providing medical professionals with a wider range of information about all the associated aspects of a disease is in the patient’s interest too.
*Menko FH et al, Birt-Hogg-Dubé syndrome: diagnosis and management. Lancet Oncol. 2009 Dec; 10(12):1199-206
**Nahorski M et al, Investigation of the Birt-Hogg-Dube tumour suppressor gene (FLCN) in familial and sporadic colorectal cancer. J Med Genet. 2010 Jun; 47(6):385-90.