Introduction: Birt-Hogg-Dubé syndrome, first described in 1977, is a rare autosomal dominant condition that commonly presents with skin lesions, including fibrofolliculomas and trichodiscomas; pulmonary cysts; spontaneous pneumothoraces; and renal cancer. We present the only known cases of intracranial vascular pathologies in patients with Birt-Hogg-Dubé syndrome.

Methods: We present 3 cases (3 female; age range: 18-50) of intracranial vascular lesions in Birt-Hogg-Dubé patients, including 2 aneurysms and 1 arteriovenous malformation, and review 1 previously reported case of carotid aplasia.

Results: Case 1 A 50-year-old Caucasian female presented to the ED complaining of a moderate headache, photophobia, nausea/vomiting, unsteady gait, and blurry vision. The patient’s past medical history was remarkable for BHD syndrome and for multiple spontaneous pneumothoraxes, renal cell carcinoma, medullary thyroid carcinoma, and skin tags. Computed tomography (CT) of the head revealed a diffuse right subarachnoid hemorrhage. Angiography revealed a 4 x 3 mm saccular aneurysm of the right internal carotid terminus. The patient reported a family history of BHD syndrome and a ruptured intracranial aneurysm. Case 2 A 25-year-old female presented to the ED with aphasia and right hemiplegia after collapsing at work. CT of the head revealed a hematoma of the left posterior frontal region and subsequent angiography was consistent with arteriovenous malformation (AVM). The patient was treated and clinically diagnosed with BHD syndrome. The patient reported a family history of BHD syndrome as well. Case 3 An 18-year Caucasian female recently diagnosed with BHD syndrome following FLCN testing, due to a genetically confirmed maternal family history of the condition, was referred to our department after magnetic resonance imaging revealed a 2 mm intracavernous internal carotid artery aneurysm.

Conclusions: We present the only known cases of intracranial vascular pathologies in BHD patients.

Patient Care: Due to the rarity of Birt-Hogg-Dubé syndrome and significant variations in its clinical presentation, it is difficult to assess whether or not Birt-Hogg-Dubé patients are predisposed to intracranial vascular pathologies. Nonetheless, we present the only known cases of intracranial vascular pathologies in BHD patients and stimulate the exploration of a possible association between intracranial vascular lesions in BHD patients. Furthermore, we hypothesize that increased transcription of hypoxia-inducible factor 1-alpha (HIF-1a), resulting from a mutated form of the protein folliculin (FLCN) transcribed by the Birt-Hogg-Dubé gene, may be associated with vascular pathogenesis in Birt-Hogg-Dubé patients and thus provide a possible molecular basis for a link between these two conditions.

Learning Objectives: By the conclusion of this session, participants should be able to: 1) Describe the importance of the association between Birt-Hogg-Dubé syndrome and intracranial vascular pathologies and the possible molecular mechanism behind the pathology 2) Discuss, in small groups, whether Birt-Hogg-Dubé patients are predisposed to intracranial vascular pathologies 3) Identify an effective solution to further study this association that can illuminate possible treatments.

References: Kapoor, R., Evins, A.I., Steitieh, D. et al. Familial Cancer (2015) 14: 595. doi:10.1007/s10689-015-9807-y