From Aldrovandi's Homuncio (1592) to Buffon s girl (1749) and the Wart Man of Tilesisus (1793): antique illustrations of mosaicism in neurofibromatosis ?

Neurofibromatosis type 1 (NF1) and type 2 both occur in mosaic (segmental) forms. When NF1 (likewise other autosomal dominant skin disorders) occurs in a linear, patchy, quadrant or otherwise localised form, two different types of mosaicism can be distinguished. The type 1 segmental involvement reflects heterozygosity for a postzygotic mutation occurring in an otherwise healthy embryo: the segmental lesions are limited to the affected area and show the same degree of severity as that found in the corresponding non mosaic trait (e.g., mosaic/segmental NF1). The type 2 segmental involvement occurs in a heterozygous embryo and reflects loss of heterozygosity that occurred at an early developmental stage. Clinically, the lesions of type 2 segmental involvement are markedly more pronounced and superimposed on a milder, non segmental, heterozygous manifestation of the same trait. In light of these concepts of mosaicism we critically reviewed (previously published) antique illustrations of presumed “full blown” NF1 sufferers. We have diagnosed as having mosaic/segmental NF1 the Indian man (“homuncio”) in the “Monstrorum Historia”cof the Italian naturalist and philosopher Ulisse Aldovrandi (1522-1605), the horned monster in the “Des monstres et prodiges” of the French surgeon Ambroise Paré (1510-1590) and the goitred woman in the “Buch der Natur” of the German naturalist Conrad von Megenberg (1303-1374). Type 2 segmental manifestations of NF1 were recognisable in the Buffon’s girl (1707-1788) and the “Wart Man” of Tilesius (1793).