Archetypical Patterns of Skin Manifestations in Neurocutaneous Disorders

Abstract

AbstractThe distribution of the cutaneous manifestations in neurocutaneous disorders is not casual; rather, it reflects predetermined patterns of skin arrangements, due to the action of the underlying genes, proteins, and/or metabolic pathways on the skin texture and appendages. These patterns of distribution are pathognomonic for each neurocutaneous disorder and can occur either in specific areas of the body (e.g., the forehead, the face, the trunk, the nails, one limb or one of more segments of the body) or following specific lines (e.g., lines of Blaschko) or taking peculiar shapes (e.g., leaf-like, ovoid, whorled, “S” or “V” shaped). These patterns of abnormal skin often mirror similar phenomena in extra-cutaneous organs/tissues, principally in the central nervous system but also in the eye, bone, heart/vessels, lung, kidney, and gut. A classification system, including several patterns of cutaneous arrangements (archetypical patterns) was proposed by the German dermatologist Rudolf Happle in 1993 and later expanded until 2014: this classification, originally meant to broadly explain (genetic and nongenetic) mosaic skin disorders and phenomena, was later expanded to explain the patterns of distribution of skin manifestations in some autosomal dominant skin disorders (genodermatoses). Currently, we recognize: (1) six archetypical patterns, including type 1 “along the lines of Blaschko” in (a) narrow or (b) large bands, type 2 “checkerboard” pattern, type 3 “phylloid” pattern, type 4 “patchy pattern without midline separation,” type 5 “lateralization” pattern, and type 6 “sash-like” pattern; (2) three less well-defined (so far unclassifiable) archetypical patterns, including (a) a diffuse hypopigmentation of the trunk versus smaller areas of normal skin on a unilateral aspect of the thorax and a segmental hyperpigmentation involving both arms and the trunk, (b) an “atypical” pattern along the Blaschko's lines, (c) the “mesotropic facial pattern,” and (iii) segmental manifestations of monogenic disorders, including (type 1) segmental areas of skin affected with the typical manifestations of a disease associated to otherwise unaffected skin and (type 2) segmental areas of skin affected with a very pronounced degree of the typical skin manifestations of a disease. In this article we review the existing literature on the early history of Blaschko's lines, the presentation of the (well-defined and unclassified) archetypical patterns and the segmental manifestations of monogenic disorders tailoring these concepts to neurocutaneous disorders.