Introduction:  Sturge-Weber syndrome is a neurocutaneous vascular malformation consisting of a facial capillary malformation, a choroid angioma of the eye and a leptomeningeal angioma.  Affected patients develop seizures, hemiparesis, visual deficits, and cognitive impairments.  We recently identified the somatic mosaic mutation in GNAQ which causes both Sturge-Weber syndrome and port-wine birthmarks. 

Methods:  Subjects (n=38) with Sturge-Weber syndrome and family member controls (n=30) provided urine samples and neurological scores at time 1, a year later and two years later.  MMP, VEGF and bFGF levels were quantified in the urine samples.  Immunohistochemistry was performed for phosphorylated ERK in cortical brain tissue samples from subjects with SWS and more affected areas compared to less affected areas.  

 Results:  Urinary MMP2 and bFGF were more likely to be seen or to be abnormally high in the urine of subjects with SWS (21/33 versus 7/20, p=0.02; and 19/38 versus 7/29, p=0.015). Furthermore, MMP9 was higher in females than males (p=0.02); this was not seen in the family control data. MMP9 correlated with total neurological clinical score r=0.523, p=0.005 and with hemiparesis score r=0.399, p=0.03.   Abnormal leptomeningeal vessels from more affected areas demonstrated increased expression of p-ERK in endothelial cells compared to expression in endothelial cells in less affected brain regions. 

Conclusions:  The hyperactivating somatic mutation in GNAQ, or alternatively blood stasis with resulting hypoxia-ischemia, may result in increased endothelial cell p-ERK expression in abnormal leptomeningeal vessels.  Increased p-ERK expression may drive increased MMP and bFGF release and these angiogenesis factors may prove useful as clinical biomarkers.