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Mosaicism and Epidermal Nevi

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Braun-Falco´s Dermatology

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Abstract

In the field of biology, a mosaic is an organism consisting of genetically different cells that have arisen from a homogeneous zygote. By contrast, a chimera develops from genetically different cell populations that originate from different zygotes. Genetic mosaics can affect all organs, but are particularly easy to recognize on the skin. For this reason, the concept of mosaicism is of peculiar importance in dermatology. In numerous dermatoses, their mosaic nature has already been proven on a cytogenetic or molecular level. Today, all nevi can be defined as genetic mosaics. On the other hand, it goes without saying that not all mosaics should be regarded as nevi, because otherwise one would have to apply the term nevus to a basal cell carcinoma or a melanoma. Examples of genomic mosaics are segmental manifestations of neurofibromatosis 1, tuberous sclerosis, or Darier disease, whereas incontinentia pigmenti, focal dermal hypoplasia, and CHILD syndrome reflect functional X-chromosome mosaicism.

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References

Patterns and Mechanisms of Cutaneous Mosaicism

  • González-Enseñat MA, Vicente A, Poo P et al (2009) Phylloid hypomelanosis and mosaic partial trisomy 13: two cases that provide further evidence of a distinct clinicogenetic entity. Arch Dermatol 14:576–578

    Google Scholar 

  • Happle R (1993) Mosaicism in human skin: understanding the patterns and mechanisms. Arch Dermatol 129:1460–1470

    CAS  PubMed  Google Scholar 

  • Happle R (2014) Mosaicism in human skin: understanding nevi, nevoid skin disorders, and cutaneous neoplasia. Springer, Berlin

    Google Scholar 

  • Happle R (2016) The categories of cutaneous mosaicism: a proposed classification. Am J Med Genet 170A:452–459

    PubMed  Google Scholar 

  • Happle R, Assim A (2001) The lines of Blaschko on the head and neck. J Am Acad Dermatol 44:612–615

    CAS  PubMed  Google Scholar 

Epigenetic X-Linked Mosaicism

  • Happle R (2006) X-chromosome inactivation: role in skin disease expression. Acta Paediatr Suppl 95(451):16–23

    PubMed  Google Scholar 

  • Happle R (2016) An unusual linear hypermelanosis reflecting lyonization in women with Börjeson-Forssman-Lehmann syndrome. J Eur Acad Dermatol Venereol 30:323–324

    Google Scholar 

  • Sun BK, Tsao H (2008) X-chromosome inactivation and skin disease. J Invest Dermatol 128:2753–2759

    CAS  PubMed  Google Scholar 

Epigenetic Autosomal Mosaicism

  • Happle R (2002) Transposable elements and the lines of Blaschko: a new perspective. Dermatology 204:4–7

    CAS  PubMed  Google Scholar 

  • Happle R (2009) Monoallelic expression on autosomes may explain an unusual heritable form of pigmentary mosaicism: a historical case revisited. Clin Exp Dermatol 34:834–837

    CAS  PubMed  Google Scholar 

Genomic Mosaicism

  • Itin PH, Buechner SA, Happle R (2000) Segmental manifestation of Darier disease: what is the genetic background in type 1 and type 2 mosaic phenotypes? Dermatology 200:254–257

    CAS  PubMed  Google Scholar 

  • Tinschert S, Naumann I, Stegmann E et al (2000) Segmental neurofibromatosis is caused by somatic mutation of the neurofibromatosis type 1 (NF1) gene. Eur J Hum Genet 8:455–459

    CAS  PubMed  Google Scholar 

Superimposed mosaicism in Autosomal Dominant Skin Diseases

  • Atzmony L, Khan HM, Lim YH et al (2019) Second-hit, post-zygotic PMVK and MVD mutations in linear porokeratosis. JAMA Dermatol[Epub ahead of print]. https://doi.org/10.1001/jamadermatol.2019.0016

  • Happle R (2001) Segmentale Typ-2-Manifestation autosomal dominanter Hautkrankheiten: Entwicklung eines neuen formalgenetischen Konzeptes. Hautarzt 562:283–287

    Google Scholar 

  • Happle R (2009) Superimposed segmental manifestation of both rare and common cutaneous disorders: a new paradigm. Actas Dermosifiliogr 100:77–85

    Google Scholar 

  • Happle R (2016) Progressive osseous heteroplasia is not a Mendelian trait but a type 2 segmental manifestation of GNAS inactivation disorders: a hypothesis. Eur J Med Genet 59:290–294

    Google Scholar 

  • Happle R, Torrelo A (2020) Superimposed mosaicism in tuberous sclerosis complex: a key to understanding all of the manifold manifestations? J Eur Acad Dermatol Venereol 34:2511–2517

    Google Scholar 

Superimposed Segmental Manifestation of Polygenic Skin Disorders

  • Happle R (2007) Superimposed segmental manifestation of polygenic skin disorders. J Am Acad Dermatol 5:690–699

    Google Scholar 

  • Happle R (2014) Superimposed segmental dermatomyositis is a juvenile disorder. Eur J Dermatol 24:291–292

    Google Scholar 

Other Acquired Dermatoses Following Blaschko’s Lines

  • Hauber K, Rose C, Bröcker EB et al (2000) Lichen striatus: clinical features and follow-up in 12 patients. Eur J Dermatol 10:536–539

    CAS  PubMed  Google Scholar 

  • Wollenberg A, Baumann L, Plewig G (1996) Linear atrophoderma of Moulin: a disease which follows Blaschko’s lines. Br J Dermatol 135:277–279

    CAS  PubMed  Google Scholar 

Didymosis

  • Happle R, King A (1999) Dominant traits may give rise to paired patches of either excessive or absent involvement. Am J Med Genet 84:176–177

    CAS  PubMed  Google Scholar 

  • Itin PH, Happle R (2002) Darier disease with paired segmental manifestation of either excessive or absent involvement: a further step in the concept of twin spotting. Dermatology 205:344–347

    PubMed  Google Scholar 

  • Rodríguez-Pazos L, Gomez-Bernal S, Loureiro M, Toribio J (2011) Type 2 segmental Darier disease with twin spot phenomenon. J Eur Acad Dermatol Venereol 25:496–497

    PubMed  Google Scholar 

  • Ruggieri M, Roggini M, Kennerknecht I et al (2011) Spectrum of skeletal abnormalities in a complex malformation syndrome with “cutis tricolor” (Ruggieri-Happle syndrome). Acta Paediatr 100:121–127

    PubMed  Google Scholar 

Revertant Mosaicism

  • Choate KA, Lu Y, Zhou J et al (2010) Mitotic recombination in patients with ichthyosis causes reversion of dominant mutations in KRT10. Science 330:94–97

    CAS  PubMed  PubMed Central  Google Scholar 

  • Kiritsi D, He Y, Pasmooij AM et al (2012) Revertant mosaicism in a human skin fragility disorder results from slipped mispairing and mitotic recombination. J Clin Invest 122:1742–1746

    CAS  PubMed  PubMed Central  Google Scholar 

  • Pasmooij AM, Pas HH, Bolling MC, Jonkman MF (2007) Revertant mosaicism in junctional epidermolysis bullosa due to multiple correcting second-site mutations in LAMB3. J Clin Invest 117:1240–1248

    CAS  PubMed  PubMed Central  Google Scholar 

Epidermal Nevi

  • Happle R, Rogers M (2002) Epidermal nevi. Adv Dermatol 8:175–201

    Google Scholar 

Therapy of Epidermal Nevi

  • Hohenleutner U, Landthaler M (1993) Laser therapy or verrucous epidermal naevi. Clin Exp Dermatol 18:124–127

    CAS  PubMed  Google Scholar 

  • Kiritsi D, Schauer F, Wölfle U et al (2014) Targeting epidermal lipids for treatment of Mendelian disorders of cornification. Orphanet J Rare Dis Mar 7(9):33. https://doi.org/10.1186/1750-1172-9-33

    Article  Google Scholar 

  • König A, Skrzypek J, Löffler H et al (2010) Donor dominance cures CHILD nevus. Dermatology 220:340–345

    PubMed  Google Scholar 

  • Paller AS, van Steensel MAM, Rodriguez-Martín M et al (2011) Pathogenesis-based therapy reverses cutaneous anomalies in an inherited disorder of cholesterol metabolism. J Invest Dermatol 131:2242–2248

    CAS  PubMed  PubMed Central  Google Scholar 

Epidermal Nevus Syndromes

  • Happle R (2010a) The group of epidermal nevus syndromes part I. well defined phenotypes. J Am Acad Dermatol 63:1–22

    PubMed  Google Scholar 

  • Happle R (2010b) The group of epidermal nevus syndromes part II. Less well defined phenotypes. J Am Acad Dermatol 63:25–30

    PubMed  Google Scholar 

First Describer

  • Abell E, Read SI (1980) Porokeratotic eccrine ostial and dermal duct naevus. Br J Dermatol 103:435–441

    CAS  PubMed  Google Scholar 

  • Albright F, Butler AM, Hampton AO et al (1937) Syndromes characterized by osteitis fibrosa disseminata, areas of pigmentation and endocrine dysfunction with precocious puberty in females: report of five cases. N Engl J Med 216:727–746

    Google Scholar 

  • Almeida H Jr, Happle R, Reginatto F et al (2011) Phacomatosis melanorosea with heterochromia of scalp hair: a new example of non-allelic twin spotting. Eur J Dermatol 21:487–489

    Google Scholar 

  • Altman J, Mehregan AH (1971) Inflammatory linear verrucous epidermal nevus. Arch Dermatol 104:385–389

    CAS  PubMed  Google Scholar 

  • Becker SW (1949) Concurrent melanosis and hypertrichosis in distribution of nevus unius lateris. Arch Dermatol 60:155–160

    CAS  Google Scholar 

  • Blaschko A (1901) Die Nervenverteilung in der Haut in ihrer Beziehung zu den Erkrankungen der Haut. In: Beilage zu den Verhandlungen der Deutschen Dermatologischen Gesellschaft. 7. Congress zu Breslau. Braumüller, Wien

    Google Scholar 

  • Bloch BR (1926) Eigentümliche, bisher nicht beschriebene Pigmentaffektion (Incontinentia pigmenti). Schweiz Med Wochenschr 56:404–405

    Google Scholar 

  • Castori M, Annessi G, Castiglia D et al (2010) Systematized organoid epidermal nevus with eccrine differentiation, multiple facial and oral congenital scars, gingival synechiae, and blepharophimosis: a novel epidermal nevus syndrome. Am J Med Genet 152A:25–31

    PubMed  Google Scholar 

  • Delleman JW, Oorthuys JWE (1981) Orbital cyst in addition to congenital cerebral and focal dermal malformations: a new entity? Clin Genet 19:191–198

    CAS  PubMed  Google Scholar 

  • Engber PB (1978) The nevus comedonicus syndrome: a case report with emphasis on associated internal manifestations. Int J Dermatol 17:745–749

    CAS  PubMed  Google Scholar 

  • Enjolras O, Mulliken JB (2000) Vascular malformations. In: Harper J, Oranje A, Prose N (eds) Textbook of pediatric dermatology. Blackwell, Oxford, pp 975–976

    Google Scholar 

  • Fantl G (1914) Lichen striatus: Beitrag zur Kenntnis der strichförmigen Hauterkrankungen. Dermatol Wochenschr 58:593–599

    Google Scholar 

  • García AV, Hafner C, Pérez-Rodríguez AG et al (2008) An epidermal nevus syndrome with cerebral involvement caused by a mosaic FGFR3 mutation. Am J Med Genet 146A:2275–2279

    Google Scholar 

  • Gobello T, Mazzanti C, Zambruno G et al (2000) New type of epidermal nevus syndrome. Dermatology 201:51–53

    CAS  PubMed  Google Scholar 

  • Goltz RW, Peterson WC, Gorlin RJ et al (1962) Focal dermal hypoplasia. Arch Dermatol 86:708–717

    CAS  PubMed  Google Scholar 

  • Grosshans E, Marot L (1990) Blaschkite de l’adulte. Ann Dermatol Venereol 117:9–15

    CAS  PubMed  Google Scholar 

  • Haberland C, Perou M (1970) Encephalocraniocutaneous lipomatosis: a new example of ectomesodermal dysgenesis. Arch Neurol 22:144–155

    CAS  PubMed  Google Scholar 

  • Happle R (1990) Ptychotropism as a cutaneous feature of the CHILD syndrome. J Am Acad Dermatol 23:763–766

    CAS  PubMed  Google Scholar 

  • Happle R (2000) Phylloid hypomelanosis is closely related to mosaic trisomy 13. Eur J Dermatol 10:511–512

    CAS  PubMed  Google Scholar 

  • Happle R (2002) Speckled lentiginous nevus syndrome: delineation of a new distinct neurocutaneous phenotype. Eur J Dermatol 12:133–135

    Google Scholar 

  • Happle R (2005) Phacomatosis pigmentovascularis revisited and reclassified. Arch Dermatol 141:385–388

    PubMed  Google Scholar 

  • Happle R (2007a) Linear Cowden nevus: a new distinct epidermal nevus. Eur J Dermatol 15:767–773

    Google Scholar 

  • Happle R (2007b) Type 2 segmental Cowden disease vs. Proteus syndrome. Br J Dermatol 156:1089–1090

    CAS  PubMed  Google Scholar 

  • Happle R (2009) Speckled lentiginous naevus: which of the two disorders do you mean? Clin Exp Dermatol 34:133–135

    Google Scholar 

  • Happle R, König A (1999) Dominant traits may give rise to paired patches of either excessive or absent involvement. Am J Med Genet 84:176–177

    CAS  PubMed  Google Scholar 

  • Happle R, König A (2001) Didymosis aplasticosebacea: coexistence of aplasia cutis congenita and nevus sebaceus may be explained as a twin spot phenomenon. Dermatology 202:246–248

    CAS  PubMed  Google Scholar 

  • Happle R, König A (2003) Cutaneous mosaicism. In: Schachner LA, Hansen RC, Happle R, Krafchik BR, Lucky AW, Paller AS (eds) Pediatric dermatology, 3rd edn. Mosby, Edinburgh, pp 368–376

    Google Scholar 

  • Happle R, Koopman RJ (1997) Becker nevus syndrome. Am J Med Genet 68:357–361

    CAS  PubMed  Google Scholar 

  • Happle R, Koch H, Lenz W (1980) The CHILD syndrome (congenital hemidysplasia with ichthyosiform erythroderma and limb defects). Eur J Pediatr 134:27–33

    CAS  PubMed  Google Scholar 

  • Happle R, Steijlen PM, Kolde G (1990) Naevus corniculatus: a new acantholytic disorder. Br J Dermatol 122:107–112

    CAS  PubMed  Google Scholar 

  • Happle R, Daniëls O, Koopman RJJ (1993) MIDAS syndrome (microphthalmia, dermal aplasia and sclerocornea): an X-linked phenotype distinct from Goltz syndrome. Am J Med Genet 47:710–713

    CAS  PubMed  Google Scholar 

  • Happle R, Mittag H, Küster W (1995) The CHILD nevus: a distinct skin disorder. Dermatology 191:210–216

    CAS  PubMed  Google Scholar 

  • Happle R, Hoffmann R, Restano I et al (1996) Phacomatosis pigmentokeratotica: a melanocytic-epidermal twin nevus syndrome. Am J Med Genet 65:363–365

    CAS  PubMed  Google Scholar 

  • Happle R, Barbi G, Eckert D et al (1997) Cutis tricolor: congenital hyper- and hypopigmented macules associated with a sporadic multisystem birth defect: an unusual example of twin spotting? J Med Genet 34:676–678

    CAS  PubMed  PubMed Central  Google Scholar 

  • Happle R, Fleiner J, Loskamp U (2004) Kerinokeratosis papulosa with a type 2 segmental manifestation. J Am Acad Dermatol 50:584–585

    Google Scholar 

  • Happle R, Metze D, Vera Casaño A (2010) Naevus lentiginosus linearis: a distinct skin disorder. Acta Derm Venereol 90:210–211

    PubMed  Google Scholar 

  • Hasegawa Y, Yasuhara M (1985) Phakomatosis pigmentovascularis type IVa. Arch Dermatol 121:651–655

    CAS  PubMed  Google Scholar 

  • Horii E, Sugiura Y, Nakamura R (1998) A syndrome of digital fibromas, facial pigmentary dysplasia, and metacarpal and metatarsal disorganization. Am J Med Genet 80:1–5

    CAS  PubMed  Google Scholar 

  • Itin PH, Happle R (2002) Darier disease with paired segmental manifestation of either excessive or absent involvement: a further step in the concept of twin spotting. Dermatology 205:344–347

    Google Scholar 

  • Ito M (1952) Studies on melanin. XI. Incontinentia pigmenti achromians: a singular case. Tohoku J Exp Med 55:57–59

    Google Scholar 

  • Jadassohn J (1895) Bemerkungen zur Histologie der systematisierten Naevi und über „Talgdrüsen-Naevi“. Arch Dermatol Syph (Wien) 33:355–394

    Google Scholar 

  • Kofmann S (1895) Ein Fall von seltener Localisation und Verteilung von Comedonen. Arch Dermatol Syph (Wien) 32:177–178

    Google Scholar 

  • McCune D, Bruch H (1937) Osteodystrophia fibrosa: report of a case in which the condition was combined with precocious puberty, pathologic pigmentation of the skin and hyperthyroidism. Am J Dis Child 54:806–848

    Google Scholar 

  • Mibelli V (1893) Forme non commune de kératodermie: “Porokeratosis”. In: Unna PG, Morris M, Leloir H et al (eds) International atlas of rare skin diseases. Voss/Lewis, Hamburg/London. IX (1893:1): 5-10, plate XXVII

    Google Scholar 

  • Moulin G, Hill MP, Guillaud V et al (1992) Bandes pigmentées atrophiques acquises suivant les lignes de Blaschko. Ann Dermatol Venereol 119:729–736

    CAS  PubMed  Google Scholar 

  • Munro CS, Wilkie AOM (1998) Epidermal mosaicism producing localised acne: somatic mutation in FGFR2. Lancet 352:704–705

    CAS  PubMed  Google Scholar 

  • Ota N, Kawamura T, Ito N (1947) Phacomatosis pigmentovascularis. Jpn J Dermatol Venerol 57:1–3

    Google Scholar 

  • Papillon-Léage E, Psaume J (1954) Une malformation héréditaire de la muqueuse buccale et freins anormaux. Rev Stomatol (Paris) 55:209–227

    Google Scholar 

  • Sapp JC, Turner JT, van de Kamp JM et al (2007) Newly delineated syndrome of congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome) in seven patients. Am J Med Genet 143A:2944–2958

    PubMed  Google Scholar 

  • Schauder S, Hanefeld F, Noske UM et al (2000) Depigmented hypertrichosis following Blaschko’s lines associated with cerebral and ocular malformations: a new neurocutaneous, autosomal lethal gene syndrome from the group of epidermal naevus syndromes. Br J Dermatol 142:1204–1207

    CAS  PubMed  Google Scholar 

  • Schimmelpenning GW (1957) Klinischer Beitrag zur Symptomatologie der Phakomatosen. Fortschr Röntgenstr 87:716–720

    CAS  Google Scholar 

  • Sulzberger MG (1927) Über eine bisher nicht beschriebene congenitale Pigmentanomalie (Incontinentia pigmenti). Arch Dermatol Syph (Wien) 154:19–32

    Google Scholar 

  • Tantcheva-Poor I, Reinhold K, Krieg T et al (2007) Trichilemmal cyst nevus: a new complex organoid epidermal nevus. J Am Acad Dermatol 57:S72–S77

    PubMed  Google Scholar 

  • Toriello HV, Lacassie Y, Droste P, Higgins JV (1993) Provisionally unique syndrome of ocular and ectodermal defects in two unrelated boys. Am J Med Genet 45:764–766

    CAS  PubMed  Google Scholar 

  • Torrelo A, Zambrano A, Happle R (2003) Cutis marmorata telangiectatica congenita and extensive mongolian spots: type 5 phacomatosis pigmentovascularis. Br J Dermatol 148:342–345

    CAS  PubMed  Google Scholar 

  • Vabres P, Sorlin A, Kholmanskikh SS et al (2019) Postzygotic inactivating mutations of RHOA cause a mosaic neuroectodermal syndrome. Nat Genet 51:1438–1441

    CAS  PubMed  PubMed Central  Google Scholar 

  • Wiedemann HR, Burgio GR, Aldenhoff P et al (1983) The Proteus syndrome: partial gigantism of the hands and/or feet, nevi, hemihypertrophy, subcutaneous tumors, macrocephaly, skull anomalies and possible accelerated growth and visceral affections. Eur J Pediatr 140:5–12

    CAS  PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Dermatology, University Hospital Freiburg, Freiburg, Germany

    Rudolf Happle

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  1. Rudolf Happle
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Correspondence to Rudolf Happle .

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Editors and Affiliations

  1. Department of Dermatology, Venerology and Allergology, University of Munich, Munich, Germany

    Gerd Plewig

  2. Department of Dermatology, Venerology and Allergology, University of Munich, Munich, Germany

    Lars French

  3. Department of Dermatology, Venerology and Allergology, University of Munich, Munich, Germany

    Thomas Ruzicka

  4. Department of Dermatology, Venerology and Allergology, University of Frankfurt, Frankfurt, Germany

    Roland Kaufmann

  5. Department of Dermatology and Allergology, University of Marburg, Marburg, Germany

    Michael Hertl

Section Editor information

  1. Department of Dermatology, University of Munich, Munich, Germany

    Lars French

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Happle, R. (2022). Mosaicism and Epidermal Nevi. In: Plewig, G., French, L., Ruzicka, T., Kaufmann, R., Hertl, M. (eds) Braun-Falco´s Dermatology. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-63709-8_58

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