Phacomatosis Pigmentovascularis

The coexistence of a widespread vascular nevus and an extensive pigmentary nevus is defined as phacomatosis pigmentovascularis (PPV). More than 250 (sporadic) cases of PPV have been so far reported, mainly in Asian or Asian-related populations: mutations in genes related to angiogenic pathways (RAS, MAPK, mTOR, PI3K/AKT, and GNAQ ) have been recently identified as the causes of this complex phenotype. In many cases, mutations in two different genes may coexist, representing the classical example of twin spotting phenomenon. PPV is usually associated with several extracutaneous anomalies including ocular manifestations (melanosis bulbi, glaucoma, iris mammillations, megalocornea, buphthalmos, strabismus, and hyperpigmentation of the conjunctiva, sclera, episclera, iris, trabecular meshwork, and choroid) and musculoskeletal alterations (limb hypertrophy, Klippel-Trenaunay type abnormalities, hemifacial hypertrophy, hemicorporal hypertrophy, macrocephaly, microcephaly, and scoliosis). Central nervous system anomalies have been reported in most of the patients and include seizure, cognitive delay, cerebral atrophy, hydrocephalus, sensorineural deafness, and intracranial hypertension, as well as migraine, pseudotumor cerebri, and intracerebral vascular malformations. More rarely, PPV has been associated with structural and/or vascular renal anomalies, hepatosplenomegaly, pyogenic granuloma, cavernous hemangioma, portal hypertension, umbilical hernia, hypoplasia of leg veins, and hypo- or hyperactivity of the immune system.