ABSTRACT
BACKGROUND: Birt-Hogg-Dubé syndrome (BHDS) is an autosomal-dominantly inherited genodermatosis that predisposes to the development of benign hair follicle tumours, lung cysts, kidney tumours, and possibly colonic cancers, due to mutations in the FLCN gene. We report cases involving a new mutation in three unrelated families. MATERIALS AND METHODS: Blood samples of three probands were submitted for a molecular diagnosis of BHDS. Following DNA extraction, FLCN gene sequencing was performed. The identified mutations were confirmed on a second sample. A cancer genetics consultation was organized and specific tests (dermatological examination, CT scan of chest and abdomen and colonoscopy) were proposed for each BHDS patient. RESULTS: FLCN gene-sequencing analysis revealed an identical complex harmful mutation in all three families. The first proband showed fibrofolliculomas (FF), a history of pneumothorax and colonic adenoma. The mutation was found in a brother and two sisters, who were asymptomatic, and in a niece with FF. The second proband showed FF. The mutation was found in her mother, who had FF. The third proband presented diffuse emphysema and very rare FF. DISCUSSION: This case report shows extremely wide intra- and interfamilial phenotype variation within individuals having a similar FLCN gene mutation. In large cohorts of BHDS patients, no genotype-phenotype correlation has been shown. This case emphasises the vital importance of presymptomatic diagnosis for each member of a BHDS family by means of a cancer genetics consultation, followed by a CT scan of the chest and abdomen, colonoscopy and annual kidney imaging.
