BHD syndrome and intracranial vascular pathologies?

The difficulty with rare diseases is determining if known pathologies are causatively linked to additional phenotypes. A recent report from Kapoor et al., (2015) hypothesises a link between BHD and intracranial vascular pathologies caused by aberrant HIF-1α activity.  Kapoor et al., present three case studies of aneurysms or hematomas in BHD patients of varying age (18-50). Previously an increase in HIF1α activity, and subsequent expression of its target VEGF, have been linked to the pathogenesis of aneurysms and vascular malformations (Lim et al., 2013). As a reduction in FLCN has been shown to result in increased HIF1α activity in the lungs of BHD patients (Preston et al., 2011) it is possible that a similar increase in HIF1α expression is occurring in other tissues. Kapoor et al., also identified a second potential pathway linking FLCN activity to vascular wall defects; namely the loss of SMAD7 inhibition on MMP-9 expression following FLCN loss (Hong et al., 2010). However further research is required to determine if there is a firm link between BHD and intracranial vascular lesions.

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