Advertisement

Mosaizismus und epidermale Nävi

  • Rudolf Happle
Chapter
Part of the Springer Reference Medizin book series (SRM)

Zusammenfassung

Als ein Mosaik im biologischen Sinne bezeichnet man einen Organismus bestehend aus genetisch verschiedenen Zellen, die aus einer homogenen Zygote hervorgegangen sind. Im Unterschied hierzu entsteht eine Chimäre aus genetisch verschiedenen Zellpopulationen, die aus verschiedenen Zygoten stammen. Ein genetisches Mosaik kann alle Organe betreffen, ist aber an der Haut besonders leicht zu erkennen. Aus diesem Grund kommt dem Mosaikkonzept in der Dermatologie besondere Bedeutung zu. Bei zahlreichen Dermatosen ist die Mosaiknatur bereits auf zytogenetischer oder molekularer Ebene bewiesen worden. So lassen sich heutzutage alle Nävi als genetische Mosaike definieren. Umgekehrt sind aber selbstverständlich keineswegs alle Mosaike als Nävi aufzufassen, denn sonst müsste man beispielsweise ein Basalzellkarzinom oder ein Melanom als Nävus bezeichnen. Andere Beispiele für Mosaike sind die Incontinentia pigmenti, das CHILD-Syndrom sowie segmentale Manifestationen von Neurofibromatose 1, tuberöser Sklerose oder Morbus Darier.

Literatur

Muster und Mechanismen kutaner Mosaike

  1. 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 14:576–578Google Scholar
  2. Happle R (1993) Mosaicism in human skin: understanding the patterns and mechanisms. Arch Dermatol 129:1460–1470CrossRefPubMedGoogle Scholar
  3. Happle R (2014) Mosaicism in human skin: understanding nevi, nevoid skin disorders, and cutaneous neoplasia. Springer, BerlinGoogle Scholar
  4. Happle R (2016) The categories of cutaneous mosaicism: a proposed classification. Am J Med Genet 170A:452–459CrossRefGoogle Scholar
  5. Happle R, Assim A (2001) The lines of Blaschko on the head and neck. J Am Acad Dermatol 44:612–615CrossRefPubMedGoogle Scholar

Epigenetische X-chromosomale Mosaike

  1. Happle R (2006) X-chromosome inactivation: role in skin disease expression. Acta Paediatr Suppl 95(451):16–23CrossRefPubMedGoogle Scholar
  2. Happle R (2016) An unusual linear hypermelanosis reflecting lyonization in women with Börjeson-Forssman-Lehmann syndrome. J Eur Acad Dermatol Venereol 30:323–324CrossRefPubMedGoogle Scholar
  3. Sun BK, Tsao H (2008) X-chromosome inactivation and skin disease. J Invest Dermatol 128:2753–2759CrossRefPubMedGoogle Scholar

Epigenetische autosomale Mosaike

  1. Happle R (2002) Transposable elements and the lines of Blaschko: a new perspective. Dermatology 204:4–7CrossRefPubMedGoogle Scholar
  2. Happle R (2009) Monoallelic expression on autosomes may explain an unusual heritable form of pigmentary mosaicism: a historical case revisited. Clin Exp Dermatol 34:834–837CrossRefPubMedGoogle Scholar

Genomische Mosaike

  1. 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 200:254–257CrossRefPubMedGoogle Scholar
  2. 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 8:455–459CrossRefPubMedGoogle Scholar

Segmentale Typ-2-Manifestation autosomal dominanter Hautkrankheiten

  1. Happle R (2001) Segmentale Typ-2-Manifestation autosomal dominanter Hautkrankheiten: Entwicklung eines neuen formalgenetischen Konzeptes. Hautarzt 562:283–287CrossRefGoogle Scholar
  2. Happle R (2009) Superimposed segmental manifestation of both rare and common cutaneous disorders: a new paradigm. Actas Dermosifiliogr 100:77–85CrossRefPubMedGoogle Scholar
  3. 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 59:290–294CrossRefPubMedGoogle Scholar

Überlagerte Segmentmanifestation polygener Hautkrankheiten

  1. Happle R (2007) Superimposed segmental manifestation of polygenic skin disorders. J Am Acad Dermatol 5:690–699CrossRefPubMedGoogle Scholar
  2. Happle R (2014) Superimposed segmental dermatomyositis is a juvenile disorder. Eur J Dermatol 24:291–292Google Scholar

Andere erworbene Dermatosen im Verlauf der Blaschko-Linien

  1. Hauber K, Rose C, Bröcker EB et al (2000) Lichen striatus: clinical features and follow-up in 12 patients. Eur J Dermatol 10:536–539PubMedGoogle Scholar
  2. Wollenberg A, Baumann L, Plewig G (1996) Linear atrophoderma of Moulin: a disease which follows Blaschko’s lines. Br J Dermatol 135:277–279CrossRefPubMedGoogle Scholar

Didymosis

  1. Happle R, König A (1999) Dominant traits may give rise to paired patches of either excessive or absent involvement. Am J Med Genet 84:176–177Google Scholar
  2. 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 205:344–347CrossRefPubMedGoogle Scholar
  3. Rodríguez-Pazos L, Gomez-Bernal S, Loureiro M, Toribio J (2011) Type 2 segmental Darier disease with twin spot phenomenon. J Eur Acad Dematol Venereol 25:496–497CrossRefGoogle Scholar
  4. 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 100:121–127CrossRefPubMedGoogle Scholar

Rückmutationsmosaik

  1. Choate KA, Lu Y, Zhou J et al (2010) Mitotic recombination in patients with ichthyosis causes reversion of dominant mutations in KRT10. Science 330:94–97CrossRefPubMedPubMedCentralGoogle Scholar
  2. 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 122:1742–1746CrossRefPubMedPubMedCentralGoogle Scholar
  3. 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 117:1240–1248CrossRefPubMedPubMedCentralGoogle Scholar

Epidermale Nävi

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

Therapie epidermaler Nävi

  1. Hohenleutner U, Landthaler M (1993) Laser therapy of verrucous epidermal naevi. Clin Exp Dermatol 18:124–127CrossRefPubMedGoogle Scholar
  2. König A, Skrzypek J, Löffler H et al (2010) Donor dominance cures CHILD nevus. Dermatology 220:340–345CrossRefPubMedGoogle Scholar
  3. 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 131:2242–2248Google Scholar

Epidermalnävus-Syndrome

  1. Happle R (2010) The group of epidermal nevus syndromes Part I. Well defined phenotypes. J Am Acad Dermatol 63:1–22CrossRefPubMedGoogle Scholar
  2. Happle R (2010) The group of epidermal nevus syndromes Part II. Less well defined phenotypes. J Am Acad Dermatol 63:25–30CrossRefPubMedGoogle Scholar

Erstbeschreiber

  1. Abell E, Read SI (1980) Porokeratotic eccrine ostial and dermal duct naevus. Br J Dermatol 103:435–441CrossRefPubMedPubMedCentralGoogle Scholar
  2. Albright F, Butler AM, Hampton AO et al (1937) Syndrome characterized by osteitis fibrosa disseminata, areas of pigmentation and endocrine dysfunction with precocious puberty in females: report of five cases. N Engl J Med 216:727–746CrossRefGoogle Scholar
  3. Altman J, Mehregan AH (1971) Inflammatory linear verrucous epidermal nevus. Arch Dermatol 104:385–389CrossRefPubMedPubMedCentralGoogle Scholar
  4. Becker SW (1949) Concurrent melanosis and hypertrichosis in distribution of nevus unius lateris. Arch Dermatol 60:155–160CrossRefGoogle Scholar
  5. Blaschko A (1901) Die Nervenverteilung in der Haut in ihrer Beziehung zu den Erkrankungen der Haut. Beilage zu den Verhandlungen der Deutschen Dermatologischen Gesellschaft. 7. Congress zu Breslau. Braumüller, WienGoogle Scholar
  6. Bloch BR (1926) Eigentümliche, bisher nicht beschriebene Pigmentaffektion (Incontinentia pigmenti). Schweiz Med Wochenschr 56:404–405Google Scholar
  7. 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:25–31CrossRefPubMedPubMedCentralGoogle Scholar
  8. Delleman JW, Oorthuys JWE (1981) Orbital cyst in addition to congenital cerebral and focal dermal malformations: a new entity? Clin Genet 19:191–198CrossRefPubMedGoogle Scholar
  9. Engber PB (1978) The nevus comedonicus syndrome: a case report with emphasis on associated internal manifestations. Int J Dermatol 17:745–749CrossRefPubMedGoogle Scholar
  10. Enjolras O, Mulliken JB (2000) Vascular malformations. In: Harper J, Oranje A, Prose N (Hrsg) Textbook of pediatric dermatology. Blackwell, Oxford, S 975–976Google Scholar
  11. Fantl G (1914) Lichen striatus: Beitrag zur Kenntnis der strichförmigen Hauterkrankungen. Dermatol Wochenschr 58:593–599Google Scholar
  12. 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:2275–2279CrossRefGoogle Scholar
  13. Goltz RW, Peterson WC, Gorlin RJ et al (1962) Focal dermal hypoplasia. Arch Dermatol 86:708–717CrossRefPubMedGoogle Scholar
  14. Grosshans E, Marot L (1990) Blaschkite de l’adulte. Ann Dermatol Venereol 117:9–15PubMedGoogle Scholar
  15. Haberland C, Perou M (1970) Encephalocraniocutaneous lipomatosis: a new example of ectomesodermal dysgenesis. Arch Neurol 22:144–155CrossRefPubMedGoogle Scholar
  16. Happle R (1990) Ptychotropism as a cutaneous feature of the CHILD syndrome. J Am Acad Dermatol 23:763–766CrossRefPubMedGoogle Scholar
  17. Happle R (2000) Phylloid hypomelanosis is closely related to mosaic trisomy 13. Eur J Dermatol 10:511–512PubMedGoogle Scholar
  18. Happle R (2002) Speckled lentiginous nevus syndrome: delineation of a new distinct neurocutaneous phenotype. Eur J Dermatol 12:133–135Google Scholar
  19. Happle R (2005) Phacomatosis pigmentovascularis revisited and reclassified. Arch Dermatol 141:385–388CrossRefPubMedGoogle Scholar
  20. Happle R (2007a) Linear Cowden nevus: a new distinct epidermal nevus. Eur J Dermatol 15:767–773Google Scholar
  21. Happle R (2007b) Type 2 segmental Cowden disease vs. Proteus syndrome. Br J Dermatol 156:1089–1090CrossRefPubMedGoogle Scholar
  22. Happle R (2009c) Speckled lentiginous naevus: which of the two disorders do you mean? Clin Exp Dermatol 34:133–135CrossRefPubMedGoogle Scholar
  23. Happle R, König A (1999) Dominant traits may give rise to paired patches of either excessive or absent involvement. Am J Med Genet 84:176–177Google Scholar
  24. Happle R, Koopman RJ (1997) Becker nevus syndrome. Am J Med Genet 68:357–361CrossRefPubMedGoogle Scholar
  25. Happle R, Koch H, Lenz W (1980) The CHILD syndrome (congenital hemidysplasia with ichthyosiform erythroderma and limb defects). Eur J Pediatr 134:27–33CrossRefPubMedGoogle Scholar
  26. Happle R, Steijlen PM, Kolde G (1990) Naevus corniculatus: a new acantholytic disorder. Br J Dermatol 122:107–112CrossRefPubMedGoogle Scholar
  27. 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 47:710–713CrossRefPubMedGoogle Scholar
  28. Happle R, Mittag H, Küster W (1995) The CHILD nevus: a distinct skin disorder. Dermatology 191:210–216CrossRefPubMedGoogle Scholar
  29. Happle R, Hoffmann R, Restano I et al (1996) Phacomatosis pigmentokeratotica: a melanocytic-epidermal twin nevus syndrome. Am J Med Genet 65:363–365CrossRefPubMedGoogle Scholar
  30. 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 34:676–678CrossRefPubMedPubMedCentralGoogle Scholar
  31. Happle R, Fleiner J, Loskamp U (2004) Kerinokeratosis papulosa with a type 2 segmental manifestation. J Am Acad Dermatol 50:584–585CrossRefGoogle Scholar
  32. Happle R, König A (2001) Didymosis aplasticosebacea: coexistence of aplasia cutis congenita and nevus sebaceus may be explained as a twin spot phenomenon. Dermtology 202:246–248CrossRefPubMedGoogle Scholar
  33. Happle R, Metze D, Vera Casaño A (2010) Naevus lentiginosus linearis: a distinct skin disorder. Acta Derm Venereol 90:210–211CrossRefPubMedGoogle Scholar
  34. Hasegawa Y, Yasuhara M (1985) Phakomatosis pigmentovascularis type IVa. Arch Dermatol 121:651–655CrossRefPubMedGoogle Scholar
  35. 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 205:344–347CrossRefPubMedGoogle Scholar
  36. Ito M (1952) Studies on melanin. XI. Incontinentia pigmenti achromians: a singular case. Tohoku J Exp Med 55:57–59CrossRefGoogle Scholar
  37. Jadassohn J (1895) Bemerkungen zur Histologie der systematisierten Naevi und über „Talgdrüsen-Naevi“. Arch Dermatol Syph 33:355–394CrossRefGoogle Scholar
  38. Kofmann S (1895) Ein Fall von seltener Localisation und Verteilung von Comedonen. Arch Dermatol Syph 32:177–178CrossRefGoogle Scholar
  39. 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 54:806–848CrossRefGoogle Scholar
  40. Mibelli V (1893) Forme non commune de kératodermie: „Porokeratosis“. In: Unna PG, Morris M, Leloir H et al (Hrsg) Internationaler Atlas seltener Hautkrankheiten. Voss/Lewis, Hamburg/London IX (1893:1): 5–10, plate XXVIIGoogle Scholar
  41. Moulin G, Hill MP, Guillaud V et al (1992) Bandes pigmentées atrophiques acquises suivant les lignes de Blaschko. Ann Dermatol Venereol 119:729–736PubMedGoogle Scholar
  42. Munro CS, Wilkie AOM (1998) Epidermal mosaicism producing localised acne: somatic mutation in FGFR2. Lancet 352:704–705CrossRefPubMedPubMedCentralGoogle Scholar
  43. Ota N, Kawamura T, Ito N (1947) Phacomatosis pigmentovascularis. Jpn J Dermatol Venerol 57:1–3Google Scholar
  44. Papillon-Léage E, Psaume J (1954) Une malformation héréditaire de la muqueuse buccale et freins anormaux. Rev Stomatol (Paris) 55:209–227Google Scholar
  45. 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:2944–2958CrossRefPubMedGoogle Scholar
  46. 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 142:1204–1207CrossRefPubMedGoogle Scholar
  47. Schimmelpenning GW (1957) Klinischer Beitrag zur Symptomatologie der Phakomatosen. Fortschr Röntgenstr 87:716–720CrossRefGoogle Scholar
  48. Sulzberger MG (1927) Über eine bisher nicht beschriebene congenitale Pigmentanomalie (Incontinentia pigmenti). Arch Dermatol Syph 154:19–32CrossRefGoogle Scholar
  49. 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–S77CrossRefPubMedGoogle Scholar
  50. Torrelo A, Zambrano A, Happle R (2003) Cutis marmorata telangiectatica congenita and extensive mongolian spots: type 5 phacomatosis pigmentovascularis. Br J Dermatol 148:342–345CrossRefPubMedGoogle Scholar
  51. 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 140:5–12CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Deutschland, ein Teil von Springer Nature 2018

Authors and Affiliations

  1. 1.Klinik für Dermatologie und VenerologieUniversitätsklinikum FreiburgFreiburgDeutschland

Section editors and affiliations

  • Michael Hertl
    • 1
  1. 1.Zentrum für HautkrankheitenMarburgGermany

Personalised recommendations