V A Kinsler1,2, O Boccara3, S Fraitag4, A Torrelo5, P Vabres6,7, A Diociaiuti8. 1. Paediatric Dermatology, Great Ormond Street Hospital for Children, London, U.K. 2. Genetics and Genomic Medicine, UCL Institute of Child Health, London, U.K. 3. Department of Dermatology and Reference Centre for Genodermatoses and Rare Skin Diseases (MAGEC), Université Paris Descartes - Sorbonne Paris Cité, Institut Imagine, Paris, France. 4. Department of Pathology, Hôpital Universitaire Necker-Enfants Malades, APHP, Paris, France. 5. Department of Dermatology, Hospital Infantil del Niño Jesús, Madrid, Spain. 6. Department of Dermatology and Reference Centre for Rare Skin Diseases, Dijon University Hospital, Dijon, France. 7. GAD, Genetics of Anomalies of Development, University of Bourgogne, Dijon, France. 8. Dermatology Unit, Bambino Gesù Children's Hospital, Rome, Italy.
Abstract
BACKGROUND: Cutaneous mosaicism is an area of dermatology in which there has been an explosion of knowledge within the current decade. This has led to fundamental changes in the understanding of the conditions in this field, and to an ongoing paradigm shift in the approach to management of mosaic skin disorders. OBJECTIVES: To lay out the general principles of mosaicism as they are currently understood, summarize the known cutaneous mosaic abnormalities of the skin with associated phenotypic and genotypic information, review the latest trials on targeted therapies and propose guidelines for the general approach to a patient with suspected mosaicism. METHODS: This was a consensus expert review as part of the European Reference Network project (ERN-Skin). CONCLUSIONS: This study provides clinicians with a practical approach to the patient with suspected mosaicism, redefines mosaicism for the modern genetic era, and proposes a new classification system based on genetic mechanism. What's already known about this topic? Cutaneous mosaicism is a complex field of dermatology that encompasses most birthmarks, and many rare syndromes. Some cutaneous patterns are known to be seen in mosaicism. Very few treatment options are available for most mosaic abnormalities of the skin. Recent high-sensitivity genetic techniques have led to an explosion of knowledge about genotype and phenotype in the literature. What does this study add? Expert consensus from the European Reference Network project. Review of knowledge of confirmed mosaic abnormalities of the skin, including cutaneous phenotype, extracutaneous associated features and genotype. Proposed new classification of mosaic abnormalities of the skin by genetic mechanism and therefore inheritance potential. Practical tips on correct sample collection and genetic investigation. Review of trials of targeted therapies. Guidelines for a practical clinical approach to the patient with suspected mosaicism.
BACKGROUND: Cutaneous mosaicism is an area of dermatology in which there has been an explosion of knowledge within the current decade. This has led to fundamental changes in the understanding of the conditions in this field, and to an ongoing paradigm shift in the approach to management of mosaic skin disorders. OBJECTIVES: To lay out the general principles of mosaicism as they are currently understood, summarize the known cutaneous mosaic abnormalities of the skin with associated phenotypic and genotypic information, review the latest trials on targeted therapies and propose guidelines for the general approach to a patient with suspected mosaicism. METHODS: This was a consensus expert review as part of the European Reference Network project (ERN-Skin). CONCLUSIONS: This study provides clinicians with a practical approach to the patient with suspected mosaicism, redefines mosaicism for the modern genetic era, and proposes a new classification system based on genetic mechanism. What's already known about this topic? Cutaneous mosaicism is a complex field of dermatology that encompasses most birthmarks, and many rare syndromes. Some cutaneous patterns are known to be seen in mosaicism. Very few treatment options are available for most mosaic abnormalities of the skin. Recent high-sensitivity genetic techniques have led to an explosion of knowledge about genotype and phenotype in the literature. What does this study add? Expert consensus from the European Reference Network project. Review of knowledge of confirmed mosaic abnormalities of the skin, including cutaneous phenotype, extracutaneous associated features and genotype. Proposed new classification of mosaic abnormalities of the skin by genetic mechanism and therefore inheritance potential. Practical tips on correct sample collection and genetic investigation. Review of trials of targeted therapies. Guidelines for a practical clinical approach to the patient with suspected mosaicism.
Authors: Deeti J Pithadia; John W Roman; Julie C Sapp; Leslie G Biesecker; Thomas N Darling Journal: J Am Acad Dermatol Date: 2020-02-07 Impact factor: 11.527
Authors: C Salas-Labadía; S Gómez-Carmona; R Cruz-Alcívar; D Martínez-Anaya; V Del Castillo-Ruiz; C Durán-McKinster; V Ulloa-Avilés; E Yokoyama-Rebollar; A Ruiz-Herrera; P Navarrete-Meneses; E Lieberman-Hernández; A González-Del Angel; D Cervantes-Barragán; C Villarroel-Cortés; A Reyes-León; D Suárez-Pérez; A Pedraza-Meléndez; A González-Orsuna; P Pérez-Vera Journal: Orphanet J Rare Dis Date: 2019-11-15 Impact factor: 4.123
Authors: Heidi Cope; Rebecca Spillmann; Jill A Rosenfeld; Elly Brokamp; Rebecca Signer; Kelly Schoch; Emily G Kelley; Jennifer A Sullivan; Ellen Macnamara; Sharyn Lincoln; Katie Golden-Grant; James P Orengo; Gary Clark; Lindsay C Burrage; Jennifer E Posey; Jaya Punetha; Amy Robertson; Joy Cogan; John A Phillips; Julian Martinez-Agosto; Vandana Shashi Journal: Mol Genet Genomic Med Date: 2020-07-30 Impact factor: 2.183