Speckled Lentiginous Nevus Syndrome

Speckled lentiginous nevus syndrome is a rare neurocutaneous phenotype, characterized by a specked lentiginous nevus, appearing as a light brown macule superimposed by multiple melanocytic nevi in the form of macules or papules with uneven distribution, associated with ipsilateral neurological and musculoskeletal abnormalities (i.e., dysesthesia, hyperhidrosis, and musculoskeletal abnormalities) occur. It represents a mosaic phenotype disorder resulting from postzygotic loss of heterozygosity, due to a localized defect in neural crest melanoblasts that originate certain areas of the skin and some ipsilateral neurological and musculoskeletal cells. Environmental and genetic factors may also play a role, but it has not been clarified how these factors behave in this syndrome.

Phacomatosis Pigmentokeratotica

In the group of the epidermal nevus syndromes, Happle defined in 1996 a separate entity characterized by the presence of an organoid epidermal nevus, sometimes showing sebaceous differentiation, and a speckled lentiginous nevus of the papular type, occasionally associated with extracutaneous anomalies including neurological, ophthalmological, and skeletal abnormalities. In particular, the syndrome is associated with mental retardation, epilepsy, deafness, hemiatrophy, dysesthesia, and hyperhidrosis, strabismus, lipodermoid of conjunctiva, coloboma and ptosis, and kyphosis, scoliosis, limb asymmetry, and hypertrophy. Rarely, hypertension, vascular abnormalities, atrioventricular block, hypophosphatemic rickets, and pheochromocytoma may occur. The organoid nevus follows the lines of Blaschko whereas the speckled lentiginous nevus is arranged in a checkerboard pattern. For this syndrome, the term “Phacomatosis Pigmentokeratotica” has been coined and, at the present, it is considered a very rare clinical entity, with less than 20 cases reported in the literature. Recent genetic findings have included this syndrome in the group of the mosaic RASopathies, after the discovery of mutations in the HRAS gene occurring in both sebaceous and vascular nevi, but not in nonaffected tissues.