The categories of cutaneous mosaicism: A proposed classification

• Published in: American journal of medical genetics. Part A 2016-02, Vol.170A (2), p.452-459
• Main Author: Happle, Rudolf
• Format: Article
• Language: English
• Subjects: cutaneous mosaicism; didymosis; disseminated mosaicism; epigenetic mosaicism; functional autosomal mosaicism; functional X-chromosome mosaicism; Humans; Male; Mosaicism - classification; nonsegmental mosaicism; patchy mosaicism without midline separation; revertant mosaicism; segmental mosaicism of lethal autosomal mutations; single point mosaicism; Skin Diseases, Genetic - classification; Skin Diseases, Genetic - genetics; Skin Diseases, Genetic - pathology; superimposed segmental mosaicism of polygenic skin disorders; twin spotting; type 1 segmental mosaicism of autosomal dominant skin disorders; type 2 segmental mosaicism of autosomal dominant skin disorders
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.37439

Mosaic disorders can most easily be studied in the skin. This article presents a comprehensive overview of the different forms of cutaneous mosaicism. Major categories are genomic versus epigenetic mosaicism and nonsegmental versus segmental mosaicism. The class of nonsegmental mosaics includes single point mosaicism as exemplified by solitary benign or malignant skin tumors; disseminated mosaicism as noted in autosomal dominant tumor syndromes such as neurofibromatosis 1; and patchy mosaicism without midline separation as found in giant melanocytic nevus. The class of segmental mosaics includes segmental manifestation of lethal genes surviving by mosaicism as noted in Proteus syndrome; type 1 segmental mosaicism of autosomal dominant skin disorders reflecting heterozygosity for a postzygotic new mutation; type 2 segmental mosaicism of autosomal dominant skin disorders reflecting loss of heterozygosity that occurred at an early developmental stage in a heterozygous embryo; and isolated or superimposed segmental mosaicism of common polygenic skin disorders such as psoriasis or atopic dermatitis. A particular form of genomic mosaicism is didymosis (twin spotting). Revertant mosaicism is recognizable as one or more areas of healthy skin in patients with epidermolysis bullosa or other serious genodermatoses. The category of epigenetic mosaicism includes several X‐linked, male lethal disorders such as incontinentia pigmenti, and the patterns of lyonization as noted in X‐linked non‐lethal disorders such as hypohidrotic ectodermal dysplasia of the Christ‐Siemens‐Touraine type. An interesting field of future research will be the concept of epigenetic autosomal mosaicism that may explain some unusual cases of autosomal transmission of linear hypo‐ or hypermelanosis. © 2015 Wiley Periodicals, Inc.