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The well\u2010known simple segmental mosaicism is characterized by a unilateral or otherwise localized arrangement of the ordinary lesions of the disorder, reflecting heterozygosity for an early postzygotic new mutation. By contrast, superimposed mosaicism is defined by a pronounced segmental involvement in a patient with ordinary non\u2010segmental lesions of the same disorder, resulting in a heterozygous embryo from loss of the corresponding wild\u2010type allele that occurred at a very early developmental stage. So far, the second category has been called \u2018type 2 segmental mosaicism\u2019, but here we propose the short and unambiguous term \u2018superimposed mosaicism\u2019. In order to render physicians familiar with the manifold manifestations of this category as noted in tuberous sclerosis, we review the following clinical designations under which cases suggesting superimposed mosaicism have been published: forehead plaque; shagreen patch; fibrous cephalic plaque; fibromatous lesion of the scalp; folliculocystic and collagen hamartoma; segmental hypomelanosis; congenital segmental lymphedema; and segmental \u2018diffuse\u2019 lipomatosis. Molecular corroboration of this genetic concept has been provided in a case of forehead plaque and in a child with shagreen patch. \u2013 Extracutaneous manifestations suggesting superimposed mosaicism include columnar tuberous brain defects; \u2018radial migration lines\u2019 or \u2018cerebral white matter migration lines\u2019 as noted by brain imaging; linear hamartomatous lesions of the tongue; fibrous dysplasia of bones including macrodactyly; and unilateral overgrowth of an arm or leg. \u2013 Remarkably, superimposed mosaicism appears to occur in tuberous sclerosis far more frequently than simple segmental mosaicism.<\/jats:p>","DOI":"10.1111\/jdv.16603","type":"journal-article","created":{"date-parts":[[2020,5,12]],"date-time":"2020-05-12T20:09:46Z","timestamp":1589314186000},"page":"2511-2517","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":22,"title":["Superimposed mosaicism in tuberous sclerosis complex: a key to understanding all of the manifold manifestations?"],"prefix":"10.1111","volume":"34","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-6338-1766","authenticated-orcid":false,"given":"R.","family":"Happle","sequence":"first","affiliation":[{"name":"Department of Dermatology Medical Center University of Freiburg Freiburg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"A.","family":"Torrelo","sequence":"additional","affiliation":[{"name":"Department. of Dermatology Hospital Infantil Universitario Ni\u00f1o Jes\u00fas Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,7,21]]},"reference":[{"key":"e_1_2_5_2_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0712397105"},{"key":"e_1_2_5_3_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI84262"},{"key":"e_1_2_5_4_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.0b013e3181e04325"},{"key":"e_1_2_5_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/3.suppl_1.1477"},{"key":"e_1_2_5_6_1","first-page":"1639","article-title":"Loss of tuberin in both subependymal giant cell astrocytomas and angiomyolipomas supports a two\u2010hit model for the pathogenesis of tuberous sclerosis tumors","volume":"151","author":"Henske EP","year":"1997","journal-title":"Am J Pathol"},{"key":"e_1_2_5_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnen\/63.12.1236"},{"key":"e_1_2_5_8_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.20764"},{"key":"e_1_2_5_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1006242"},{"key":"e_1_2_5_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.a.37439"},{"key":"e_1_2_5_11_1","first-page":"628","article-title":"Unilateral tuberous sclerosis complex","volume":"14","author":"Mashhood AA","year":"2004","journal-title":"J Coll Physicians Surg Pak"},{"key":"e_1_2_5_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41436-019-0520-3"},{"key":"e_1_2_5_13_1","doi-asserted-by":"publisher","DOI":"10.1001\/archderm.1997.03890480025004"},{"key":"e_1_2_5_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1525-1470.2006.00245.x"},{"key":"e_1_2_5_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0001-7310(08)74972-X"},{"key":"e_1_2_5_16_1","doi-asserted-by":"crossref","first-page":"37","DOI":"10.4103\/idoj.IDOJ_60_17","article-title":"Tuberous sclerosis complex and diffuse lipomatosis: case report of a rare association","volume":"9","author":"Mittal A","year":"2018","journal-title":"Indian Dermatol Online J"},{"key":"e_1_2_5_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2008.440"},{"key":"e_1_2_5_18_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2133.1996.d01-923.x"},{"key":"e_1_2_5_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.14765"},{"key":"e_1_2_5_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.62.3.292"},{"key":"e_1_2_5_21_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2014.938"},{"key":"e_1_2_5_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.c.31649"},{"key":"e_1_2_5_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2017.12.027"},{"key":"e_1_2_5_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ad.2018.02.041"},{"key":"e_1_2_5_25_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamadermatol.2019.1972"},{"key":"e_1_2_5_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/jdv.13853"},{"key":"e_1_2_5_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jaad.2011.04.002"},{"key":"e_1_2_5_28_1","first-page":"109","article-title":"Pourquoi les g\u00e9nodermoses autosomiques dominantes ont\u2010elles deux expressions segmentaires diff\u00e9rentes? 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