This RDCRC proposal focuses on three relatively rare vascular malformations that are poorly understood in terms of biological mechanisms, resource-intensive to manage effectively and with high probability of serious neurological morbidity. Each disease is characterized by the development of a distinct category of vascular malformations and a unique spectrum of clinical and phenotypic outcomes, for which biological risk factors are either poorly understood or completely unknown. The identification of such risk factors that relate to disease progression would be of immediate significance for patient surveillance and for optimizing management. Further, although there are no specific medical therapies for these diseases, appropriate treatment (efficacy) trials will require risk stratification for selection and surrogate outcomes for trial development. The general effort is focused on the establishment of research grade, relational, scalable clinical databases to conduct observational or interventional trials. Further, we will identify novel markers for disease progression. The combined effort will foster new approaches to the diagnosis, prevention, and treatment of these three rare diseases, providing novel means of risk stratification that will be applicable to future clinical trials. The three projects synergize with one another in these common goals and objectives, their use of common infrastructure elements, and overlapping but complementary expertises of the investigators. For the Sturge-Weber Syndrome (SWS) project, our database will be capture SWS patients across the nation as they are seen at Sturge-Weber Foundation (SWF) Centers of Excellence. Thus, our database will be the first national SWS database with longitudinal clinical data. In addition, we will investigate urine biomarkers of angiogenesis as potential predictors of SWS disease progression and severity.
Our final aim will attempt to discover the molecular genetic basis for the syndrome, starting from a long-standing hypothesis first formulated by Rudolf Happle 20 years ago, but untested until now due to technical hurdles. Happle proposed that SWS is caused by somatic mutation in a critical gene mutations in which cannot be passed through the germline. We build on this hypothesis to propose that the somatic mutation might lie within a gene encoding a critical angiogenesis factor. Using high resolution SNP genotyping in affected and unaffected tissue from SWS patients, we propose a systematic approach to mapping and identifying the causative gene(s) for SWS. The illumination of the molecular genetic etiology of SWS will suggest new avenues for future development of therapy.

National Institute of Health (NIH)
National Institute of Neurological Disorders and Stroke (NINDS)
Specialized Center--Cooperative Agreements (U54)
Project #
Application #
Study Section
Special Emphasis Panel (ZRG1-HOP-Y)
Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
University of California San Francisco
San Francisco
United States
Zip Code
Choquet, Hélène; Nelson, Jeffrey; Pawlikowska, Ludmila et al. (2014) Association of cardiovascular risk factors with disease severity in cerebral cavernous malformation type 1 subjects with the common Hispanic mutation. Cerebrovasc Dis 37:57-63
Reidy, Teressa Garcia; Suskauer, Stacy J; Bachur, Cathy D et al. (2014) Preliminary reliability and validity of a battery for assessing functional skills in children with Sturge-Weber syndrome. Childs Nerv Syst 30:2027-36
Cheng, Kyle H Y; Mariampillai, Adrian; Lee, Kenneth K C et al. (2014) Histogram flow mapping with optical coherence tomography for in vivo skin angiography of hereditary hemorrhagic telangiectasia. J Biomed Opt 19:086015
Lance, Eboni I; Sreenivasan, Aditya K; Zabel, T Andrew et al. (2013) Aspirin use in Sturge-Weber syndrome: side effects and clinical outcomes. J Child Neurol 28:213-8
Sreenivasan, Aditya K; Bachur, Catherine D; Lanier, Kira E et al. (2013) Urine vascular biomarkers in Sturge-Weber syndrome. Vasc Med 18:122-8
Lopez, Jonathan; Yeom, Kristen W; Comi, Anne et al. (2013) Case report of subdural hematoma in a patient with Sturge-Weber syndrome and literature review: questions and implications for therapy. J Child Neurol 28:672-5
Siddique, Laila; Sreenivasan, Aditya; Comi, Anne M et al. (2013) Importance of utilizing a sensitive free thyroxine assay in Sturge-Weber syndrome. J Child Neurol 28:269-74
Arora, Karun S; Quigley, Harry A; Comi, Anne M et al. (2013) Increased choroidal thickness in patients with Sturge-Weber syndrome. JAMA Ophthalmol 131:1216-9
Shirley, Matthew D; Tang, Hao; Gallione, Carol J et al. (2013) Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med 368:1971-9
Lo, Warren; Marchuk, Douglas A; Ball, Karen L et al. (2012) Updates and future horizons on the understanding, diagnosis, and treatment of Sturge-Weber syndrome brain involvement. Dev Med Child Neurol 54:214-23

Showing the most recent 10 out of 11 publications