Phenotypic variability in a family with capillary malformations caused by a mutation in the RASA1 gene

Hereditary capillary malformations are known to be caused by mutations in the RASA1 gene. The associated phenotype is still subject of debate. The purpose of this study was to conduct a RASA1 mutation analysis in the family that led to the initial discovery of the 5q locus, and to delineate the associated phenotype. A novel truncating mutation was identified in all clinically affected individuals and in none of the unaffected members. The associated phenotype was widely variable; all individuals had multifocal CM with at least one area of high flow. Various additional features were observed, some previously reported and others novel, including limb overgrowth, varicosities, possible lymphatic malformations, localized hyperhidrosis and exercise induced redness. The cause of this wide intramutational phenotypic variability remains to be elucidated.