Mosaic Neurocutaneous Disorders and Their Causes

Cutis tricolor: a literature review and report of five new cases

“…This phenomenon has been reported so far either (18): (I) as an purely cutaneous trait (3,5,7,11,17,18); (II) as a part of a complex malformation phenotype (Ruggieri-Happle syndrome, RHS) (18,(21)(22)(23) including distinct facial (a peculiar facial phenotype consisting in coarse, asymmetric and later in adolescence elongated face, thick and brushy eyebrows, hypertelorism, deep nasal bridge with large bulbous nose and anteverted nostrils, low-set ears, large phyltrum), eye (congenital cataract), skeletal (small skull, dystrophic vertebrae, and mildly bowed long bones), nervous system [corpus callosum anomalies, white matter abnormalities (i.e., delayed myelination), holoprosencephaly and cerebellar anomalies] and systemic abnormalities (2,3,6,8,(11)(12)(13)(14)16,18,19); (III) as a distinct type with multiple, disseminated smaller skin macules (cutis tricolor parvimaculata) (9,15,18) [different from the autosomal dominant congenital hypo-and hyperpigmented macules (Westerhof syndrome; MIM # 154000)]; and (IV) in association with other skin disturbances [e.g., cutis marmorata telangectasica congenita (phacomatosis achromico-melano-marmorata)] or in the context of other skin disorders (e.g., ataxia-telangiectasia and phacomatosis pigmentovascularis, PPV) or neurocutaneous phenotypes (4,10,13,20).…”

“…In their 17-year-old boy they described congenital hyper-and hypopigmented macules confined to circumscribed body segments on a background of normal intermediate skin complexion in association with multiple birth defects (2). Ruggieri (3) subsequently expanded the cutaneous phenotype by including cases with abnormal paired pigmentation in the form of large patches (in the form of a yet unclassified archetypical pattern of cutaneous mosaicism) (1,23,(26)(27)(28) or streaks (sash-like pattern of cutaneous mosaicism) (1,23) diffusely involving the body associated (case 2) (3) or not (case 1) (3) to systemic defects. The spectrum of extracutaneous manifestations further expanded in recent years including specific facial dysmorphic, skeletal and brain abnormalities (6,(11)(12)(13)(14)16,19).…”

Early history of neurofibromatosis type 2 and related forms: earliest descriptions of acoustic neuromas, medical curiosities, misconceptions, landmarks and the pioneers behind the eponyms

“…The earliest examples of individuals having (skin) nodules resembling neurofibromas (or plexiform neurofibromas) [1,6,60,64,66,67,68,70,71] can be traced in (a description contained in) the Ebers Papyrus from Ancient Egypt (1.500 BC) [72], in a Hellenistic statuette (Smyrna,323 BC) [33,46,60], in the coinage of the Parthian kings (247 BC) [3,75,89], in the manuscript called Cotton Tiberius B.v. (fourth century AD) [66,100,101] and in a thirteenth century drawing by a Cistercian monk named Heinricus [51,54]. Additional descriptions of "grotesque" or distorted individuals (or monsters) are traced in the fifteenth century "Buch der Natur" (Book of Nature) by Konrad von Magenberg [54,100,101], in the sixteenth century treatise "Des monstres et prodiges" ("On Monsters and Marvels") by Ambroise Paré [54,66] and in a xylograph by José de Ribeira also known as "Lo Spagnoletto" (the Little Spaniard) [66,100,101].…”

“…The first clinical description of a case is attributed to the Italian physician and naturalist Ulisse Aldrovandi [8,66,79,85], who in the "Monstrorum Historia" (1592 AD) described a man of short stature (homuncio) with a large tumour resembling an isolated plexiform neurofibroma [6,37,48,100] (first possible example of mosaic NF1) [64,67,68,70]. A further example is likely portrayed in a large figure of a head carved in lindenwood, which supports one of the walls under the galleries and balconies of the library of the Cistercian monastery of Waldassen in Germany and known as the (oriental) "curious fool" [25,60,61,66,100,101].…”

“…NF1, NF2 or schwannomatosis), thus resembling the so-called type 2 segmental manifestations of autosomal dominant traits [34,36] (i.e. a very pronounced (segmental) involvement limited to a restricted area of the body superimposed on the non-segmental phenotype vs. the type 1 segmental manifestations, which are characterised by a true mosaic/localised form of a disease) [35,64,67,68,70].…”