title: Genetically diagnosed Birt-Hogg-Dubé syndrome and familial cerebral cavernous malformations in the same individual: a case report.
abstract: When faced with an unusual clinical feature in a patient with a Mendelian disorder, the clinician may entertain the possibilities of either the feature representing a novel manifestation of that disorder or the co-existence of a different inherited condition. Here we describe an individual with a submandibular oncocytoma, pulmonary bullae and renal cysts as well as multiple cerebral cavernous malformations and haemangiomas. Genetic investigations revealed constitutional mutations in FLCN, associated with Birt-Hogg-Dubé syndrome (BHD) and CCM2, associated with familial cerebral cavernous malformation. Intracranial vascular pathologies (but not cerebral cavernous malformation) have recently been described in a number of individuals with BHD (Kapoor et al. in Fam Cancer 14:595-597, 10.1007/s10689-015-9807-y , 2015) but it is not yet clear whether they represent a genuine part of that conditions' phenotypic spectrum. We suggest that in such instances of potentially novel clinical features, more extensive genetic testing to consider co-existing conditions should be considered where available. The increased use of next generation sequencing applications in diagnostic settings is likely to lead more cases such as this being revealed.
authors.affiliation: Department of Medical Genetics, University of Cambridge, Cambridge, UK. Jww39@medschl.cam.ac.uk.
authors.forename: James
authors.identifier: 0000-0003-2747-4006
authors.initials: J
authors.lastname: Whitworth
authors.affiliation: Department of Radiology, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Brian
authors.initials: B
authors.lastname: Stausbøl-Grøn
authors.affiliation: Department of Clinical Genetics, Aarhus University Hospital, Aarhus, Denmark.
authors.forename: Anne-Bine
authors.initials: AB
authors.lastname: Skytte
mesh_terms: D058249:Birt-Hogg-Dube Syndrome / Q000175:diagnosis / Q000235:genetics*; D002352:Carrier Proteins / Q000235:genetics*; D005260:Female; D020786:Hemangioma, Cavernous, Central Nervous System / Q000235:genetics*; D006801:Humans; D008875:Middle Aged; D009154:Mutation; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D025521:Tumor Suppressor Proteins / Q000235:genetics*
chemical_list: C502544:CCM2 protein, human; D002352:Carrier Proteins; C476078:FLCN protein, human; D011518:Proto-Oncogene Proteins; D025521:Tumor Suppressor Proteins
keywords: Birt–Hogg–Dubé syndrome; Cerebral cavernous malformation; Double heterozygote; Genetics