Birt-Hogg-Dubé syndrome: novel FLCN frameshift deletion in daughter and father with renal cell carcinomas

Familial Cancer
Ernst NäfGabor Matyas

Abstract

Germline mutation of the FLCN gene causes Birt-Hogg-Dubé syndrome (BHD), a rare autosomal dominant condition characterized by skin fibrofolliculomas, lung cysts, spontaneous pneumothorax and renal tumours. We identified a hitherto unreported pathogenic FLCN frameshift deletion c.563delT (p.Phe188Serfs*35) in a family of a 46-year-old woman presented with macrohematuria due to bilateral chromophobe renal carcinomas. A heritable renal cancer was suspected due to the bilaterality of the tumour and as the father of this woman had suffered from renal cancer. Initially, however, BHD was overlooked by the medical team despite the highly suggestive clinical presentation. We assume that BHD is underdiagnosed, at least partially, due to low awareness of this variable condition and to insufficient use of appropriate genetic testing. Our study indicates that BHD and FLCN testing should be routinely considered in patients with positive family or personal history of renal tumours. In addition, we demonstrate how patients and their families can play a driving role in initiating genetic diagnosis, presymptomatic testing of at-risk relatives, targeted disease management, and genetic counselling of rare diseases such as BHD.

References

Dec 1, 1977·Archives of Dermatology·A R BirtW J Dubé
Apr 1, 1996·Der Hautarzt; Zeitschrift für Dermatologie, Venerologie, und verwandte Gebiete·A A SchachtschabelR Happle
Dec 10, 2002·Journal of Medical Genetics·S K KhooS Richard
Apr 12, 2005·The Journal of Urology·Christian P PavlovichW Marston Linehan
Apr 27, 2005·American Journal of Human Genetics·Laura S SchmidtW Marston Linehan
Jun 16, 2005·Journal of the National Cancer Institute·Cathy D VockeW Marston Linehan
Jul 6, 2007·The Journal of Investigative Dermatology·Edward M LeterFred H Menko
Dec 5, 2009·The Lancet Oncology·Fred H MenkoUNKNOWN European BHD Consortium
Jun 5, 2010·Journal of Medical Genetics·Michael S NahorskiEamonn R Maher
Nov 28, 2012·Familial Cancer·Lindsay A Middelton
Jan 12, 2013·Familial Cancer·Marigje VernooijBarry J Coull
May 25, 2013·Familial Cancer·Lambros StamatakisW Marston Linehan
May 30, 2013·Familial Cancer·Nishant GuptaFrancis X McCormack
Dec 19, 2014·Orphanet Journal of Rare Diseases·Patrick R BenusiglioUNKNOWN French National Cancer Institute Inherited Predisposition to Kidney Cancer Network

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Methods Mentioned

BETA
biopsy
PCR

Software Mentioned

LOVD
HGMD

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