• Ute Moog, Ute Felbor, Cristina Has, and Birgit Zirn.
• Institute of Human Genetics. University Hospital Heidelberg, Heidelberg; Institute of Human Genetics, University of Greifswald and Interfaculty Institute for Genetics and Functional Genomics, Greifswald University, Greifswald; Department of Dermatology and Venereology, University Medical Center Freiburg, Albert-Ludwigs-Universität Freiburg, Freiburg; genetikum®, Genetische Beratung und Diagnostik, Stuttgart.
• Dtsch Arztebl Int. 2020 Feb 21; 116 (8): 119125119-125.

BackgroundGenetic mosaics arise through new mutations occurring after fertiliza- tion (i.e., postzygotic mutations). Mosaics have been described in recent years as the cause of many different disorders; many of these are neurocutaneous diseases and syndromal developmental disorders, each with a characteristic phenotype. In some of these disorders, there is a genetic predisposition to the development of tumors. This article is intended as an overview of selected mosaic diseases.MethodsThis review is based on publications retrieved by a selective search in PubMed, with particular attention to recent articles in high-ranking journals dealing with asymmetric growth disturbances, focal brain malformations, mosaic diseases due to dysregulation of the RAS/RAF signaling pathway (mosaic RASopathies), and vascular malformations.ResultsThe identification of postzygotic mutations has led to the reclassification of traditional disease entities and to a better understanding of their pathogenesis. Diagnosis is aided by modern next-generation sequencing (NGS) techniques that allow the detection even of low-grade mosaics. Many mosaic mutations are not detectable in blood, but only in the affected tissue, e.g., the skin. Genetic mosaic diseases often manifest themselves in the skin and brain, and by facial dysmorphism, asymmetrical growth disturbances, and vascular malformations.ConclusionThe possibility of a mosaic disease should be kept in mind in the diag- nostic evaluation of patients with asymmetrical growth disturbances, focal neuronal migration disturbances, vascular malformations, and linear skin abnormalities. The demonstration of a postzygotic mutation often affords relief to the parents of an affected child, since this means that there is no increased risk for recurrence of the same disorder in future children. Correct classification is important, as molecular available for certain mosaic diseases, e.g., PIK3CA-related overgrowth spectrum (PROS) disorder.

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