Compositions and methods for treatment of Sturge-Weber Syndrome, Klippel-Trenaunay-Weber Syndrome, Port-Wine Stains and related neurocutaneous disorders are provided. Cell lines having the somatic mutation GNAQ p.Arg183Gln amino acid substitution, which was found to be the cause of port-wine stains (prevalence 1 in 300) and Sturge-Weber syndrome are also provided. Compositions and methods for treatment of uveal melanoma are also provided herein. Methods of screening novel compounds and compositions useful in increasing RGS2 and/or RGS4 expression and function in vitro, and for treatment of Sturge-Weber Syndrome, Klippel-Trenaunay-Weber Syndrome, Port-Wine Stains and related neurocutaneous disorders are provided are also provided.