BHD: Colon Cancer and Its Association With a Rare Genetic Syndrome

Abstract

Burt-Hogg-Dube (BHD) is a rare autosomal dominant genodermatosis characterized by benign tumors of the hair follicle known as fibrofolliculomas, trichodiscomas and acrochordons, pulmonary cysts with recurrent and frequently spontaneous pneumothoraces, and increased susceptibility to renal cancers. We present a case of a woman who presented with early onset CRC and pulmonary cysts, and was found to have BHD on subsequent germline testing. Our goal is to promote the use of multi-gene tumor testing combined with a thorough family and personal history to diagnose underlying familial syndromes early, and subsequently modify screening protocols in those patients at risk for syndromic cancers. A 46yo woman was diagnosed with CRC via colonoscopy. Her mother had two spontaneous pneumothoraces; family history was otherwise unremarkable. Staging CT demonstrated a 0.4cm left lower lobe pulmonary nodule and small left lower lobe cysts vs pneumatoceles (see figure 1). Genomic tumor testing (Foundation Medicine, Cambridge, MA) reported tumor mutations in FLCN S333fs*56 and TP53 C238Y. She was referred to our institution's Genetic Clinic where she underwent multi-gene panel testing for inherited colon cancer genes, in addition to the FLCN mutation found in her tumor. A germline mutation in FLCN (S333fs*56) was confirmed and post-test counselling was performed. Multi-gene tumor testing can identify candidate genes for germline testing, to be used in combination with a good personal and family history to identify rare heritable cancer syndromes. In this case, the history of recurrent spontaneous pneumothoraces in the family coupled with the FLCN mutation identified in the tumor was suggestive of BHD.Although the association between BHD and CRC has not been yet established, any patient presenting with early onset cancer warrants a workup for a possible inherited familial syndrome as many syndromes are still poorly described. As the use of NGS broadens, more diagnoses of rare syndromes such as BHD will be made, and additional phenotypic manifestations may possibly be identified. The diagnosis of BHD in this patient necessitates increasing surveillance to monitor the evolution of her syndrome. Early diagnosis of inherited genetic syndromes is crucial to prevent unnecessary morbidity and mortality of patients, as many of these syndromes are associated with cancers that require stricter screening protocols, which can be implemented as soon as a diagnosis is made.1625 Figure 1. Chest CT with lower lobe pulmonary nodule and LLL cysts