Mixed Vascular Nevus Syndrome

Abstract

Mixed vascular nevus (or nevus vascularis mixtus) represents an admixture of cutaneous vascular malformations of the telangiectatic type and angiospastic spots of nevus anemicus. It can occur as a purely cutaneous trait or as a hallmark of a neurocutaneous phenotype, the so-called mixed vascular nevus syndrome. The latter is characterized by the combination of paired vascular twin nevi and brain abnormalities of the Dyke–Davidoff–Masson type, consisting of crossed cerebral/cerebellar hemiatrophy with hypoplasia of the ipsilateral cerebral vessels, and homolateral hypertrophy of the skull and sinuses (hyperpneumatization) with contralateral hemispheric hypertrophy. In other cases, the paired vascular twin nevi and brain malformations of the Dyke–Davidoff–Masson type occur in association with systemic abnormalities consisting of facial asymmetry, skeletal anomalies, and disorders of autoimmunity. In 2014, Happle proposed to name the syndrome with the eponym Ruggieri–Leech's syndrome after the first two authors who reported (independently) this phenotype in different patients.Pathogenically, this complex phenotype suggests that embryonic pairing and somatic recombination of recessive (didymotic) alleles controlling the balance between constriction (i.e., nevus anemicus) and dilatation (i.e., nevus telangiectaticus) of blood vessels could be the primary event causing the phenomena of cutaneous and brain vascular twin spotting and the paired phenomena of skull hyperpneumatization versus hypertrophy and brain megalencephaly/colpocephaly versus cortical dysplasia.