Cutaneous Mosaicism

A mosaic is an individual composed of two or more genetically different cell lines originating from one homogeneous zygote. This short but precise definition, based on a genetic concept applicable to all pluricellular living organisms, has a great impact on human skin diseases, as it is the hallmark of a great number of human diseases with extremely variable presentations. The skin is a privileged organ for the study of mosaicism because the skin lesions are visible, readily accessible to gene testing and may be associated with internal lesions in organs embryologically related to the skin structures affected by mosaicism.

Overall, every skin lesion caused by a postzygotic pathogenic variant is considered a mosaic lesion. In a broad sense, every skin nevus or even tumoral lesion, regardless of age of appearance and clinical expression (including both patterned and non-patterned lesions), is the result of mosaicism, with different mosaic mechanisms involved, ranging from lethal mutations occurring during embryonic development to second-hit mutations in nonlethal dominant genes causing tumor-prone syndromes. The genetic concept of mosaicism thus provides an explanation for the pathogenesis of both rare and common skin diseases. In a more restricted sense, the group of mosaic conditions encompasses skin lesions that most often appear at birth or in infancy, and follow fixed embryonic patterns or reflect the migration of cell clones during embryonic development.

During the past decades, theories based on observation were formulated, mainly proposed by Prof. Rudolf Happle. Advances in genetic testing have corroborated most of Happle's hypotheses, and many laboratories worldwide are now able to document, at the molecular level, the mutational origin of the vast majority of skin mosaic conditions. While some preliminary studies have demonstrated the potential of targeted therapies acting at different levels in mosaic skin conditions, it is expected that in the future, most mosaic conditions will be treatable with targeted drugs administered orally or topically.

This Special Issue of JEACP is dedicated to Cutaneous Mosaicism and is authored by some of the most reputed European experts in the field. It offers an overview of the basic mechanisms of cutaneous mosaicism, the clinical approach to mosaic disorders and reviews the most important groups of mosaic skin conditions. I hope our readers will enjoy the outstanding work carried out by our contributors.

The author declares no conflicts of interest.