Skip to main content
SpringerLink
Log in

Nevi

  • Chapter
  • First Online:
Mosaicism in Human Skin

Abstract

Mosaic skin disorders can be divided into three major groups: i) nevi; ii) nevoid skin disorders that do not fulfill the criteria of true nevi; and iii) benign or malignant neoplastic skin lesions. According to present knowledge, nevi are visible, circumscribed, long-lasting lesions of the skin or the neighboring mucosa, reflecting mosaicism. With the exception of melanocytic nevi, they do not show neoplastic growth. They never show malignant neoplasia. (Obviously, some nevi may show secondary malignant growth, but such tumors do no longer represent nevi.) Most nevi reflect the action of a lethal gene that can only survive in an admixture with wild-type cells. There are, however, many important exceptions from this rule, such as the nonlethal postzygotic mutations causing the epidermal nevus of the epidermolytic type. Pigmentary nevi: This group includes melanocytic nevi and other pigmentary lesions reflecting mosaicism. Common small melanocytic nevi represent a polygenic trait. Molecular analysis has revealed postzygotic allelic loss involving various genes such as BRAF, NRAS, BRCA1, MC1R or IRF4, thus corroborating the concept of mosaicism.– In “atypical” melanocytic nevi (formerly called “dysplastic nevi”) the number of such events of LOH is rather high. Spitz nevi appear to be genetically different because BRAF mutations are absent, whereas HRAS mutations are frequently noted. By way of exception, all of these small nevi may show a segmental arrangement. Large or giant melanocytic nevi may sometimes represent a superimposed mosaic manifestation of a polygenic trait consisting of multiple small melanocytic nevi. – Papular nevus spilus is an entity that can clearly be distinguished from macular nevus spilus. Both types are arranged in a checkerboard pattern. – The linear lentiginous nevus is characterized by complete absence of any hypo- or hyperpigmented background . – Nevus cesius (segmental dermal melanocytosis) has also been called nevus fuscucoeruleus, or “aberrant Mongolian spot” which is an obsolete name. – Linear hypermelanosis in broad bands is a characteristic feature of McCune-Albright syndrome. – The linear lesions of “hypomelanosis of Ito” are no nosological entity but merely a cutaneous marker of many different states of mosaicism. The same is true for so-called “linear and whorled nevoid hypermelanosis” and for phylloid hypermelanosis, whereas phylloid hypomelanosis represents a distinct entity reflecting a mosaic trisomy 13q. – A checkerboard arrangement of hyper- or hypomelanosis arranged has rarely been reported. Epidermal nevi can be divided into two large groups, keratinocytic nevi and organoid nevi. Most of the keratinocytic nevi have today been elucidated at the molecular level. Types of so far unknown etiology include inflammatory linear verrucous epidermal nevus, nevus corniculatus, nevus kerinokeratoticus, and the hystrix-lke epidermal nevus of NEVADA syndrome. Keratinocytic nevus syndromes with a known molecular basis include Proteus syndrome, CLOVES syndrome, type 2 segmental PTEN hamartoma syndrome, and CHILD syndrome. Organoid epidermal nevus syndromes with a known molecular cause comprise Schimmelpenning syndrome (including phacomatosis pigmentikeratotica) and the “porokeratotic eccrine nevus syndrome” representing a mosaic manifestation of KID syndrome. Organoid nevus syndromes of unknown etiology include angora hair nevus syndrome (Schauder syndrome), nevus comedonicus syndrome, Becker nevus syndrome, and Castori syndrome. The acne nevus of Munro reflects a postzygotic FGFR2 mutation and thus represents a mosaic manifestation of Apert syndrome. Vascular nevi: The frequently used name “capillary malformation” is an umbrella term being unsuitable to denote any of the different capillary nevi such as nevus flammeus, nevus roseus, rhodoid nevus, cutis marmorata telangiectatica congenita, livedo reticularis congenita, angiokeratoma circumscriptum, segmentally arranged angioma serpiginosum, and nevus anemicus. – Facial nevi flammei are most likely not arranged according to the trigeminal dermatomes. Sturge-Weber syndrome and Klippel-Trenaunay syndrome most likely represent one single entity that may be called Sturge-Weber-Klippel-Trenaunay syndrome. – Nevus roseus is a lateralized birthmark characterized by its pale-pink color. – The rhodoid nevus is a hallmark of the autosomal dominant trait, rhodoid nevus syndrome (including both “capillary malformation-arteriovenous malformation” and “capillary malformation without arteriovenous malformation” (OMIM 608354), being caused by RASA1 mutations. Rhodoid nevi are lighter than nevus flammeus, but darker than nevus roseus. They are often surrounded by an anemic halo. – Cutis marmorata telangiectatica congenita (including van Lohuizen syndrome) should be distinguished from livedo reticularis congenita (including “macrocephaly-capillary malformation syndrome”). – The venous nevi represent a group of different disorders. Large venous nevi occur sporadically and are arranged in a segmental pattern with a strict midline separation. Small venous nevi occur as an autosomal dominant trait being caused by TEK mutations. The venous nevus of the Servelle-Martorell type represents a segmentally arranged, huge phlebectasia with hyperplasia of the involved limb. Connective tissue nevi are often noted in patients with tuberous sclerosis in the form of large collagen nevi that are described under various names such as shagreen patch, forehead patch, cobblestone nevus or fibrous hamartoma of infancy. All of these lesions represent a type 2 segmental manifestation of the disorder. – The linear collagen nevus that has also been described under the name “papulolinear collagenoma” follows the system of Blaschko’s lines. – Multiple, disseminated, small elastin-rich nevi are a characteristic feature of Buschke-Ollendorff syndrome, whereas large segmental lesions (“juvenile elastoma”) represent a type 2 mosaic involvement of the disorder. – Within the group of autosomal dominant Ehlers-Danlos syndromes, examples of both type 1 and type 2 segmental manifestation have been documented. Fatty tissue nevi: Two different types of such nevi can be distinguished. Nevus lipomatosus superficialis is a well known disorder that tends to be arranged on the trunk in a linear pattern. Involvement of the scalp is extremely rare. By contrast, nevus psiloliparus is a less well known skin lesion consisting of a flat and hairless lesion involving the scalp. In the past it has often been confused with nevus sebaceus. Nevus psiloliparus is a hallmark of encephalocraniocutaneous lipomatosis, a sporadically occurring multisystem birth defect. Its molecular basis is so far unknown but the hypothesis of a lethal mutation surviving by mosaicism will most likely be corroborated in the near future.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 119.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Agrawal S, Garg VK, Sah SP, Agarwalla A (2001) Acne in Becker’s nevus. Int J Dermatol 40:583–585

    CAS  PubMed  Google Scholar 

  2. Akelma AZ, Cizmeci MN, Kanburoglu MK, Mete E (2012) A diagnostic dilemma: inflammatory linear verrucous epidermal nevus versus linear psoriasis. J Pediatr 162:879

    PubMed  Google Scholar 

  3. Al Hawsawi K, Al Aboud K, Al Aboud D, Al Githami A (2003) Linear angioma serpiginosum. Pediatr Dermatol 20:167–168

    PubMed  Google Scholar 

  4. Alexander GL (1972) Sturge-Weber syndrome. In: Vinken PJ, Bruyn GW (eds) Handbook of clinical neurology, vol 14. North Holland Publishing Company, Amsterdam, pp 223–240

    Google Scholar 

  5. Alimurung FM, Lapenas D, Willis I, Lang P (1979) Zebra-like hyperpigmentation in an infant with multiple congenital defects. Arch Dermatol 115:878–881

    CAS  PubMed  Google Scholar 

  6. Aloi FG, Molinero A (1987) Nevus comedonicus with epidermolytic hyperkeratosis. Dermatologica 174:140–143

    CAS  PubMed  Google Scholar 

  7. Alomari AI (2009) Characterization of a distinct syndrome that associates complex truncal overgrowth, vascular, and acral anomalies: a descriptive study of 18 cases of CLOVES syndrome. Clin Dysmorphol 18:1–7

    PubMed  Google Scholar 

  8. Al-Oudah N, Al Rujaii A, Al-Rikabi AC (2009) Nevus lipomatosus of the scalp mimicking sebaceous nevus: report of an unusual case. Eur J Pediatr Dermatol 19:135–138

    Google Scholar 

  9. Alsaleh QA, Nanda A, Hassab-el-Naby HM, Sakr MF (1994) Familial inflammatory linear verrucous epidermal nevus (ILVEN). Int J Dermatol 33:52–54

    CAS  PubMed  Google Scholar 

  10. Antaya RJ, Keller RA, Wilkerson JA (1995) Placental nevus cells associated with giant congenital pigmented nevi. Pediatr Dermatol 12:260–262

    CAS  PubMed  Google Scholar 

  11. Apel HP, Kuhlwein A, Jänner M (1986) Porokeratosis linearis unilateralis (linear porokeratosis). Hautarzt 37:284–286

    CAS  PubMed  Google Scholar 

  12. Azuma I (1984) Congenital glaucoma. Klin Monbl Augenheilkd 184:287–289

    CAS  PubMed  Google Scholar 

  13. Bayramgurler D, Filinte D, Kiran R (2008) Angioma serpiginosum with sole involvement. Eur J Dermatol 18:708–709

    PubMed  Google Scholar 

  14. Bechara FG, Happle R, Altmeyer P, Grabbe S, Jansen T (2006) Angiokeratoma circumscriptum arranged in a systematized band-like pattern suggesting mosaicism. J Dermatol 33:489–491

    PubMed  Google Scholar 

  15. Biesecker LG, Happle R, Mulliken JB, Weksberg R, Graham JM Jr, Viljoen DL, Cohen MM Jr (1999) Proteus syndrome: diagnostic criteria, differential diagnosis, and patient evaluation. Am J Med Genet 84:389–395

    CAS  PubMed  Google Scholar 

  16. Blinkenberg EO, Brendehaug A, Sandvik AK, Vatne O, Hennekam RC, Houge G (2007) Angioma serpiginosum with oesophageal papillomatosis is an X-linked dominant condition that maps to Xp11.3-Xq12. Eur J Hum Genet 15:543–547

    CAS  PubMed  Google Scholar 

  17. Boente Mdel C, Asial RA, Happle R (2008) Phacomatosis pigmentokeratotica: a follow-up report documenting additional cutaneous and extracutaneous anomalies. Pediatr Dermatol 25:76–80

    PubMed  Google Scholar 

  18. Boente MC, Asial R, Primc NB, Happle R (2013) Angora hair nevus: a further case of an unusual epidermal nevus representing a hallmark of angora hair nevus syndrome (Schauder syndrome). J Dermatol Case Rep 7:49–51

    Google Scholar 

  19. Bolognia JL, Orlow SJ, Glick SA (1994) Lines of Blaschko. J Am Acad Dermatol 31:157–190, quiz 190–152

    CAS  PubMed  Google Scholar 

  20. Boon LM, Mulliken JB, Vikkula M (2005) RASA1: variable phenotype with capillary and arteriovenous malformations. Curr Opin Genet Dev 15:265–269

    CAS  PubMed  Google Scholar 

  21. Bourdeaut F, Hérault A, Gentien D, Pierron G, Ballet S, Reynaud S, Paris R, Schleiermacher G, Baumann C, Philippe-Chomette P, Gauthier-Villars M, Peuchmaur M, Radvanyi F, Delattre O (2010) Mosaicism for oncogenic G12D KRAS mutation associated with epidermal nevus, polycystic kidneys and rhabdomyosarcoma. J Med Genet 47:859–862

    PubMed  Google Scholar 

  22. Bouthors J, Vantyghem MC, Manouvrier-Hanu S, Soudan B, Proust E, Happle R, Piette F (2006) Phacomatosis pigmentokeratotica associated with hypophosphataemic rickets, pheochromocytoma and multiple basal cell carcinomas. Br J Dermatol 155:225–226

    CAS  PubMed  Google Scholar 

  23. Bygum A, Petkov Y, Graakjaer J, Jensen UB, Fagerberg C (2012) Phylloid hypermelanosis in a child with psychomotor delay, cicatricial alopecia, hearing loss and polythelia. Acta Derm Venereol 92:191–192

    PubMed  Google Scholar 

  24. Cambiaghi S, Gianotti R, Caputo R (2007) Widespread porokeratotic eccrine ostial and dermal duct nevus along Blaschko lines. Pediatr Dermatol 24:162–167

    PubMed  Google Scholar 

  25. Cardot-Leccia N, Italiano A, Monteil MC, Basc E, Perrin C, Pedeutour F (2007) Naevus lipomatosus superficialis: a case report with a 2p24 deletion. Br J Dermatol 156:380–381

    CAS  PubMed  Google Scholar 

  26. Castori M, Annessi G, Castiglia D, Buffa V, Paradisi A, Cascone P, Zambruno G, Grammatico P, Paradisi M (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 A 152A:25–31

    PubMed  Google Scholar 

  27. Chen W, Liu TJ, Yang YC, Happle R (2006) Angioma serpiginosum arranged in a systematized segmental pattern suggesting mosaicism. Dermatology 213:236–238

    PubMed  Google Scholar 

  28. Child FJ, Werring DJ, Vivier AW (1998) Proteus syndrome: diagnosis in adulthood. Br J Dermatol 139:132–136

    CAS  PubMed  Google Scholar 

  29. Cil Y, Yildiz H, Simsek HA (2011) Sacral nevus lipomatosus cutaneous superficialis. J Cutan Aesthet Surg 4:161–162

    PubMed  Google Scholar 

  30. Collin B, Taylor IB, Wilkie AO, Moss C (2007) Fibroblast growth factor receptor 3 (FGFR3) mutation in a verrucous epidermal naevus associated with mild facial dysmorphism. Br J Dermatol 156:1353–1356

    CAS  PubMed  Google Scholar 

  31. Cosendey FE, Martinez NS, Bernhard GA, Dias MF, Azulay DR (2010) Becker nevus syndrome. An Bras Dermatol 85:379–384

    PubMed  Google Scholar 

  32. Cullen SI (1979) Localized Ehlers-Danlos syndrome. Arch Dermatol 115:332–333

    CAS  PubMed  Google Scholar 

  33. Dammert K (1965) Angiokeratosis naeviformis – a form of naevus telangiectaticus lateralis (naevus flammeus). Dermatologica 130:17–39

    CAS  PubMed  Google Scholar 

  34. Danarti R, Happle R, König A (2001) Paradominant inheritance may explain familial occurrence of cutis marmorata telangiectatica congenita. Dermatology 203:208–211

    CAS  PubMed  Google Scholar 

  35. Danarti R, König A, Bittar M, Happle R (2007) Inverse Klippel-Trenaunay syndrome: review of cases showing deficient growth. Dermatology 214:130–132

    PubMed  Google Scholar 

  36. Delfino LN, Fariello G, Quattrocchi CC, Aiello C, Menchini L, Devito R, Zama M, Claps D, Vigevano F, Longo D (2011) Encephalocraniocutaneous lipomatosis (ECCL): neuroradiological findings in three patients and a new association with fibrous dysplasia. Am J Med Genet A 155A:1690–1696

    PubMed  Google Scholar 

  37. Deutsch J, Weissenbacher G, Widhalm K, Wolf G, Barsegar B (1976) Combination of the syndrome of Sturge-Weber and the syndrome of Klippel-Trenaunay (author’s transl). Klin Pädiatr 188:464–471

    CAS  PubMed  Google Scholar 

  38. Devillers C, Quatresooz P, Hermanns-Lê T, Szepetiuk G, Lemaire R, Piérard-Franchimont C, Piérard GE (2011) Hypomelanosis of Ito: pigmentary mosaicism with immature melanosome in keratinocytes. Int J Dermatol 50:1234–1239

    PubMed  Google Scholar 

  39. Dhar SU, Robbins-Furman P, Levy ML, Patel A, Scaglia F (2009) Tetrasomy 13q mosaicism associated with phylloid hypomelanosis and precocious puberty. Am J Med Genet A 149A:993–996

    PubMed  Google Scholar 

  40. Dhouib A, Hanquinet S, La Scala GC (2013) Encephalocraniocutaneous lipomatosis: magnetic resonance imaging findings in a child. J Pediatr 163:297–297.e1

    Google Scholar 

  41. Dockx L, Lowenthal A, Van Bogaert L (1956) A congenital pigmentary syndrome close to incontinentia pigmenti with oligophrenia and multiple osteoarticular malformations. Rev Neurol (Paris) 95:48–54

    CAS  Google Scholar 

  42. Donati P, Trincone S, Cota C, Paolini F, Venuti A (2011) Kerinokeratosis papulosa-like lesions in an adult man with homozygous polymorphism of EVER 2. Eur J Dermatol 21:288–289

    PubMed  Google Scholar 

  43. Droitcourt C, Adenis-Lamarre E, Ezzedine K, Taïeb A, Jouary T (2009) Blaschkolinear congenital melanocytic nevus. Dermatology 219:182–183

    PubMed  Google Scholar 

  44. Dubiel W, Kiehlmann I, Happle R (2013) Linear collagen nevus: an unusual connective tissue nevus. Acta Derm Venereol (Epub ahead of print) doi: 10.2340/00015555-1747

    Google Scholar 

  45. Easton JA, Donnelly S, Kamps MA, Steijlen PM, Martin PE, Tadini G, Janssens R, Happle R, van Geel M, van Steensel MA (2012) Porokeratotic eccrine nevus may be caused by somatic connexin26 mutations. J Invest Dermatol 132:2184–2191

    CAS  PubMed  Google Scholar 

  46. Eerola I, Boon LM, Mulliken JB, Burrows PE, Dompmartin A, Watanabe S, Vanwijck R, Vikkula M (2003) Capillary malformation-arteriovenous malformation, a new clinical and genetic disorder caused by RASA1 mutations. Am J Hum Genet 73:1240–1249

    CAS  PubMed  Google Scholar 

  47. Effendy I, Happle R (1992) Linear arrangement of multiple congenital melanocytic nevi. J Am Acad Dermatol 27:853–854

    CAS  PubMed  Google Scholar 

  48. Elder DE, Green MH, Dt G, Kraemer KH, Clark WH Jr (1982) The dysplastic nevus syndrome: our definition. Am J Dermatopathol 4:455–460

    CAS  PubMed  Google Scholar 

  49. Enjolras O, Ciabrini D, Mazoyer E, Laurian C, Herbreteau D (1997) Extensive pure venous malformations in the upper or lower limb: a review of 27 cases. J Am Acad Dermatol 36:219–225

    CAS  PubMed  Google Scholar 

  50. Esmarch F, Kulenkampff D (1885) Die elephantiastischen Formen: eine umfassende Darstellung der angeborenen und erworbenen Elephantiasis sowie aller verwandten Leiden. J. F. Richter, Hamburg, pp 235–236, Table XXV

    Google Scholar 

  51. Faletra F, Berti I, Tommasini A, Pecile V, Cleva L, Alberini E, Bruno I, Gasparini P (2012) Phylloid pattern of hypomelanosis closely related to chromosomal abnormalities in the 13q detected by SNP array analysis. Dermatology 225:294–297

    CAS  PubMed  Google Scholar 

  52. Ferreira PS, Valente NY, Nico MM (2013) Multiple filiform keratoses and nodules in a 10-year-old girl. Pediatr Dermatol 30:261–262

    PubMed  Google Scholar 

  53. Franceschini P, Licata D, Di Cara G, Guala A, Franceschini D, Genitori L (2000) Macrocephaly-cutis marmorata telangiectatica congenita without cutis marmorata? Am J Med Genet 90:265–269

    CAS  PubMed  Google Scholar 

  54. García-Vargas A, Hafner C, Pérez-Rodríguez AG, Rodríguez-Rojas LX, González-Esqueda P, Stoehr R, Hernández-Torres M, Happle R (2008) An epidermal nevus syndrome with cerebral involvement caused by a mosaic FGFR3 mutation. Am J Med Genet A 146A:2275–2279

    PubMed  Google Scholar 

  55. Gerbig AW, Zala L, Hunziker T (1995) Angioma serpiginosum, a skin change along Blaschko lines? Hautarzt 46:847–849

    CAS  PubMed  Google Scholar 

  56. Girard C, Bessis D (2006) Papulolinear collagenoma. J Am Acad Dermatol 54:S240

    PubMed  Google Scholar 

  57. Goldstone S, Samitz MH, Carter DM (1967) 1. Giant cerebriform nevus of the scalp with malignant melanoma and metastases. 2. Multiple intradermal nevi with macular atrophy of many lesions. Arch Dermatol 95:137

    Google Scholar 

  58. Golitz LE, Weston WL (1979) Inflammatory linear verrucous epidermal nevus: association with epidermal nevus syndrome. Arch Dermatol 115:1208–1209

    CAS  PubMed  Google Scholar 

  59. Gomez MR, Bebin EM (1987) Sturge-Weber syndrome. In: Gomez MR (ed) Neurocutaneous diseases: a practical approach. Butterworths, Boston, pp 356–167

    Google Scholar 

  60. Gonzalez ME, Burk CJ, Barbouth DS, Connelly EA (2009) Macrocephaly-capillary malformation: a report of three cases and review of the literature. Pediatr Dermatol 26:342–346

    PubMed  Google Scholar 

  61. González-Enseñat MA, Vicente A, Poo P, Catalá V, Pérez-Iribarne MM, Fuster C, Geán E, Happle R (2009) Phylloid hypomelanosis and mosaic partial trisomy 13: two cases that provide further evidence of a distinct clinicogenetic entity. Arch Dermatol 145:576–578

    PubMed  Google Scholar 

  62. Gorlin RJ, Cohen MMJ, Hennekam RCM (eds) (2001) Syndromes of the head and neck. Oxford University Press, Oxford

    Google Scholar 

  63. Groesser L, Herschberger E, Ruetten A, Ruivenkamp C, Lopriore E, Zutt M, Langmann T, Singer S, Klingseisen L, Schneider-Brachert W, Toll A, Real FX, Landthaler M, Hafner C (2012) Postzygotic HRAS and KRAS mutations cause nevus sebaceous and Schimmelpenning syndrome. Nat Genet 44:783–787

    CAS  PubMed  Google Scholar 

  64. Groesser L, Herschberger E, Sagrera A, Shwayder T, Flux K, Ehmann L, Wollenberg A, Torrelo A, Bagazgoitia L, Diaz-Ley B, Tinschert S, Oschlies I, Siner S, Mickler M, Toll A, Landthaler M, Real FX, Hafner C (2013) Phacomatosis pigmentokeratotica is caused by a postzygotic HRAS mutation in a multipotent progenitor cell. J Invest Dermatol 133:1998–2003

    CAS  PubMed  Google Scholar 

  65. Groesser L, Vogt T, Happle R, Herschberger E, Mickler M, Landthaler M, Hafner C (2012) Nevus marginatus revisited: a combined organoid and non-organoid epidermal nevus caused by HRAS mutation. Br J Dermatol 168:892–894

    Google Scholar 

  66. Hafner C, Hartmann A, van Oers JM, Stoehr R, Zwarthoff EC, Hofstaedter F, Landthaler M, Vogt T (2007) FGFR3 mutations in seborrheic keratoses are already present in flat lesions and associated with age and localization. Mod Pathol 20:895–903

    CAS  PubMed  Google Scholar 

  67. Hafner C, Landthaler M, Happle R, Vogt T (2008) Nevus marginatus: a distinct type of epidermal nevus or merely a variant of nevus sebaceus? Dermatology 216:236–238

    PubMed  Google Scholar 

  68. Hafner C, López-Knowles E, Luis NM, Toll A, Baselga E, Fernández-Casado A, Hernández S, Ribé A, Mentzel T, Stoehr R, Hofstaedter F, Landthaler M, Vogt T, Pujol RM, Hartmann A, Real FX (2007) Oncogenic PIK3CA mutations occur in epidermal nevi and seborrheic keratoses with a characteristic mutation pattern. Proc Natl Acad Sci U S A 104:13450–13454

    CAS  PubMed  Google Scholar 

  69. Hafner C, Toll A, Gantner S, Mauerer A, Lurkin I, Acquadro F, Fernandez-Casado A, Zwarthoff EC, Dietmaier W, Baselga E, Parera E, Vicente A, Casanova A, Cigudosa J, Mentzel T, Pujol RM, Landthaler M, Real FX (2012) Keratinocytic epidermal nevi are associated with mosaic RAS mutations. J Med Genet 49:249–253

    CAS  PubMed  Google Scholar 

  70. Hafner C, Toll A, Real FX (2011) HRAS mutation mosaicism causing urothelial cancer and epidermal nevus. N Engl J Med 365:1940–1942

    CAS  PubMed  Google Scholar 

  71. Hafner C, van Oers JM, Vogt T, Landthaler M, Stoehr R, Blaszyk H, Hofstaedter F, Zwarthoff EC, Hartmann A (2006) Mosaicism of activating FGFR3 mutations in human skin causes epidermal nevi. J Clin Invest 116:2201–2207

    CAS  PubMed  Google Scholar 

  72. Hafner C, Vogt T, Landthaler M, Müsebeck J (2008) Somatic FGFR3 and PIK3CA mutations are present in familial seborrhoeic keratoses. Br J Dermatol 159:214–217

    CAS  PubMed  Google Scholar 

  73. Hamm H, Happle R (1986) Inflammatory linear verrucous epidermal nevus (ILVEN) in a mother and her daughter. Am J Med Genet 24:685–690

    CAS  PubMed  Google Scholar 

  74. Hamm H, Happle R (1986) Mixed vascular nevus: report of 4 cases. Hautarzt 37:388–392

    CAS  PubMed  Google Scholar 

  75. Happle R (1986) Cutaneous manifestation of lethal genes. Hum Genet 72:280

    CAS  PubMed  Google Scholar 

  76. Happle R (1986) The McCune-Albright syndrome: a lethal gene surviving by mosaicism. Clin Genet 29:321–324

    CAS  PubMed  Google Scholar 

  77. Happle R (1987) Lethal genes surviving by mosaicism: a possible explanation for sporadic birth defects involving the skin. J Am Acad Dermatol 16:899–906

    CAS  PubMed  Google Scholar 

  78. Happle R (1989) Gregor Mendel and the dysplastic nevi. Hautarzt 40:70–76

    CAS  PubMed  Google Scholar 

  79. Happle R (1990) Nichterbliche Genodermatosen. Hautarzt 41:104–109

    Google Scholar 

  80. Happle R (1992) Paradominant inheritance: a possible explanation for Becker’s pigmented hairy nevus. Eur J Dermatol 2:39–40

    Google Scholar 

  81. Happle R (1993) Pigmentary patterns associated with human mosaicism: a proposed classification. Eur J Dermatol 3:170–174

    Google Scholar 

  82. Happle R (1995) What is a nevus? A proposed definition of a common medical term. Dermatology 191:1–5

    CAS  PubMed  Google Scholar 

  83. Happle R (1995) Epidermal nevus syndromes. Semin Dermatol 14:111–121

    CAS  PubMed  Google Scholar 

  84. Happle R (1999) Neurocutaneous diseases. In: Freedberg IM, Eisen AZ, Wolff K et al (eds) Dermatology in general medicine. Mc-Graw-Hill, New York, pp 2131–2148

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  86. Happle R (2001) Phylloid hypomelanosis and mosaic trisomy 13: a new etiologically defined neurocutaneous syndrome. Hautarzt 52:3–5

    CAS  PubMed  Google Scholar 

  87. Happle R (2001) Buschke-Ollendorff syndrome: early, unilateral and pronounced involvement may be explained as a type 2 segmental manifestation. Eur J Dermatol 11:505

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  90. Happle R (2003) Sturge-Weber-Klippel-Trenaunay syndrome: what’s in a name? Eur J Dermatol 13:223

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  92. Happle R (2005) Nevus roseus: a distinct vascular birthmark. Eur J Dermatol 15:231–234

    PubMed  Google Scholar 

  93. Happle R (2006) Viewpoint 2 in: What is the biological basis of pattern formation in skin lesions? Exp Dermatol 15:553–557

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  95. Happle R (2007) Linear Cowden nevus: a new distinct epidermal nevus. Eur J Dermatol 17:133–136

    PubMed  Google Scholar 

  96. Happle R (2008) What is a capillary malformation? J Am Acad Dermatol 59:1077–1079

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  99. Happle R (2009) Angioma serpiginosum is not caused by PORCN mutations. Eur J Hum Genet 17:881–882; author reply 882

    CAS  PubMed  Google Scholar 

  100. Happle R (2010) Giant melanocytic nevus may be explained as a superimposed patchy manifestation of a polygenic trait. Dermatology 221:30–33

    PubMed  Google Scholar 

  101. Happle R (2010) Phylloid hypermelanosis: an unusual form of pigmentary mosaicism. Dermatology 220:183–185

    PubMed  Google Scholar 

  102. Happle R (2010) The group of epidermal nevus syndromes Part I. Well defined phenotypes. J Am Acad Dermatol 63:1–22, quiz 23–24

    PubMed  Google Scholar 

  103. Happle R (2010) The group of epidermal nevus syndromes Part II. Less well defined phenotypes. J Am Acad Dermatol 63:25–30, quiz 31–22

    PubMed  Google Scholar 

  104. Happle R (2010) The rhodoid nevus: a proposed term for a so far unnamed capillary malformation. Dermatology 221:317–319

    PubMed  Google Scholar 

  105. Happle R (2011) Didymosis cesioanemica: an unusual counterpart of phacomatosis cesioflammea. Eur J Dermatol 21:471

    PubMed  Google Scholar 

  106. Happle R (2013) Phacomatosis pigmentokeratotica is a “pseudodidymosis”. J Invest Dermatol 133:1923–1925

    Google Scholar 

  107. Happle R (2013) Nevus sebaceus is a mosaic RASopathy. J Invest Dermatol 133:597–600

    CAS  PubMed  Google Scholar 

  108. Happle R, Danarti R (2010) CHILD syndrome vs. unilateral psoriasis. Int J Dermatol 49:847–848

    PubMed  Google Scholar 

  109. Happle R, Fleiner J, Loskamp U (2004) Kerinokeratosis papulosa with a type 2 segmental manifestation. J Am Acad Dermatol 50:S84–S85

    PubMed  Google Scholar 

  110. Happle R, Franco-Guío MF, Santacoloma-Osorio G (2012) Phylloid hypermelanosis: a cutaneous marker of several different disorders? Pediatr Dermatol. doi: 10.1111/pde.12053 [E-pub ahead of print]

  111. Happle R, Hörster S (2004) Nevus psiloliparus: report of two nonsyndromic cases. Eur J Dermatol 14:314–316

    PubMed  Google Scholar 

  112. Happle R, König A (1999) Familial naevus sebaceus may be explained by paradominant transmission. Br J Dermatol 141:377

    CAS  PubMed  Google Scholar 

  113. Happle R, Küster W (1998) Nevus psiloliparus: a distinct fatty tissue nevus. Dermatology 197:6–10

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  116. Happle R, Rogers M (2002) Epidermal nevi. Adv Dermatol 18:175–201

    PubMed  Google Scholar 

  117. Happle R, Steijlen PM (1993) Encephalocraniocutaneous lipomatosis: a non-hereditary mosaic phenotype. Hautarzt 44:19–22

    CAS  PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  119. Happle R, Traupe H, Vakilzadeh F, Macher E (1982) Arguments in favor of a polygenic inheritance of precursor nevi. J Am Acad Dermatol 6:540–543

    CAS  PubMed  Google Scholar 

  120. Harit D, Aggarwal A (2010) CLOVE syndrome with nevus unis lateris: report of a case. Pediatr Dermatol 27:311–312

    PubMed  Google Scholar 

  121. Hernández-Núñez A, Borbujo J, Córdoba S, Martínez-Morán C, Martínez-Sánchez D, Romero-Maté A (2011) Nevus anemicus of the cheek with ipsilateral melanosis bulbi: an unusual example of didymosis. Eur J Dermatol 21:597–598

    PubMed  Google Scholar 

  122. Hershkovitz D, Bergman R, Sprecher E (2008) A novel mutation in RASA1 causes capillary malformation and limb enlargement. Arch Dermatol Res 300:385–388

    CAS  PubMed  Google Scholar 

  123. Hofer T (2006) Does inflammatory linear verrucous epidermal nevus represent a segmental type 1/type 2 mosaic of psoriasis? Dermatology 212:103–107

    PubMed  Google Scholar 

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

    CAS  PubMed  Google Scholar 

  125. Hohenleutner U, Wlotzke U, Konz B, Landthaler M (1995) Carbon dioxide laser therapy of a widespread epidermal nevus. Lasers Surg Med 16:288–291

    CAS  PubMed  Google Scholar 

  126. Houge G, Oeffner F, Grzeschik KH (2008) An Xp11.23 deletion containing PORCN may also cause angioma serpiginosum, a cosmetic skin disease associated with extreme skewing of X-inactivation. Eur J Hum Genet 16:1027–1028

    CAS  PubMed  Google Scholar 

  127. Hussein MR, Roggero E, Tuthill RJ, Wood GS, Sudilovsky O (2003) Identification of novel deletion loci at 1p36 and 9p22-21 in melanocytic dysplastic nevi and cutaneous malignant melanomas. Arch Dermatol 139:816–817

    PubMed  Google Scholar 

  128. Hussein MR, Wood GS (2002) Molecular aspects of melanocytic dysplastic nevi. J Mol Diagn 4:71–80

    PubMed  Google Scholar 

  129. Ishimoto S, Ito K, Matsuzaki M, Kimura M (2002) Sensorineural hearing loss with intracranial venous malformations in Klippel-Trenaunay syndrome. Ann Otol Rhinol Laryngol 111:558–562

    PubMed  Google Scholar 

  130. Jamora MJ, Celis MA (2008) Generalized porokeratotic eccrine ostial and dermal duct nevus associated with deafness. J Am Acad Dermatol 59:S43–S45

    PubMed  Google Scholar 

  131. Jinawath N, Zambrano R, Wohler E, Palmquist MK, Hoover-Fong J, Hamosh A, Batista DA (2011) Mosaic trisomy 13: understanding origin using SNP array. J Med Genet 48:323–326

    PubMed  Google Scholar 

  132. Kalter DC, Griffiths WA, Atherton DJ (1988) Linear and whorled nevoid hypermelanosis. J Am Acad Dermatol 19:1037–1044

    CAS  PubMed  Google Scholar 

  133. Karuppal R, Raman RV, Valsalan BP, Gopakumar T, Kumaran CM, Vasu CK (2008) Servelle-Martorell syndrome with extensive upper limb involvement: a case report. J Med Case Reports 2:142

    Google Scholar 

  134. Kim DH, Park SB, Lee Y, Im M, Seo YJ, Choi SH, Lee JH (2012) Encephalocraniocutaneous lipomatosis without neurologic anomalies. Ann Dermatol 24:476–478

    PubMed  Google Scholar 

  135. Kinsler VA, Abu-Amero S, Budd P, Jackson IJ, Ring SM, Northstone K, Atherton DJ, Bulstrode NW, Stanier P, Hennekam RC, Sebire NJ, Moore GE, Healy E (2012) Germline melanocortin-1-receptor genotype is associated with severity of cutaneous phenotype in congenital melanocytic nevi: a role for MC1R in human fetal development. J Invest Dermatol 132:2026–2032

    CAS  PubMed  Google Scholar 

  136. Kinsler VA, Thomas AC, Ishida M, Bulstrode NW, Loughlin S, Hing S, Chalker J, McKenzie K, Abu-Amero S, Slater O, Chanudet E, Palmer R, Morrogh D, Stanier P, Healy E, Sebire NJ, Moore GE (2013) Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by post-zygotic mutations in codon 61 of NRAS. J Invest Dermatol 133: 2229–2236

    Google Scholar 

  137. Köse O, Huseynov S, Demiriz M (2012) Giant Mongolian macules with bilateral ocular involvement: case report and review. Dermatology 224:126–129

    PubMed  Google Scholar 

  138. Krieg T, Landthaler M, Ihme A, Wolff HH, Braun-Falco O (1984) Cutis hyperelastica circumscripta: a case report with a morphologic study. Hautarzt 35:415–417

    CAS  PubMed  Google Scholar 

  139. Kumakiri M, Katoh N, Miura Y (1980) Angioma serpiginosum. J Cutan Pathol 7:410–421

    CAS  PubMed  Google Scholar 

  140. Kurek KC, Luks VL, Ayturk UM, Alomari AI, Fishman SJ, Spencer SA, Mulliken JB, Bowen ME, Yamamoto GL, Kozakewich HP, Warman ML (2012) Somatic mosaic activating mutations in PIK3CA cause CLOVES syndrome. Am J Hum Genet 90:1108–1115

    CAS  PubMed  Google Scholar 

  141. Kuske H, Baumgartner P (1962) Angiokeratoma corporis naeviforme. Dermatologica 124:303

    Google Scholar 

  142. Küster W, König A (1999) Hypomelanosis of Ito: no entity, but a cutaneous sign of mosaicism. Am J Med Genet 85:346–350

    PubMed  Google Scholar 

  143. Lang SC, Bauer B, Bröcker EB, Hamm H (2010) Naevus trichilemmocysticus - the first paediatric case of a newly delineated organoid naevus. J Eur Acad Dermatol Venereol 24:1485–1487

    CAS  PubMed  Google Scholar 

  144. Larralde M, Boggio P, Abad ME, Corbella C, Happle R (2011) Nevus trichilemmocysticus: report of a new case of a recently recognized entity. Pediatr Dermatol 28:286–289

    PubMed  Google Scholar 

  145. Leech SN, Taylor AE, Ramesh V, Birchall D, Lynch SA (2004) Widespread capillary malformation associated with global developmental delay and megalencephaly. Clin Dysmorphol 13:169–172

    PubMed  Google Scholar 

  146. Levinsohn JL, Tian LC, Boyden LM, McNiff JM, Narayan D, Loring ES, Yun D, Sugarman JL, Overton JD, Mane SM, Lifton RP, Paller AS, Wagner AM, Antaya RJ, Choate KA (2013) Whole-exome sequencing reveals somatic mutations in HRAS and KRAS, which cause nevus sebaceus. J Invest Dermatol 133:827–830

    CAS  PubMed  Google Scholar 

  147. Limaye N, Boon LM, Vikkula M (2009) From germline towards somatic mutations in the pathophysiology of vascular anomalies. Hum Mol Genet 18:R65–R74

    CAS  PubMed  Google Scholar 

  148. Lindhurst MJ, Sapp JC, Teer JK, Johnston JJ, Finn EM, Peters K, Turner J, Cannons JL, Bick D, Blakemore L, Blumhorst C, Brockmann K, Calder P, Cherman N, Deardorff MA, Everman DB, Golas G, Greenstein RM, Kato BM, Keppler-Noreuil KM, Kuznetsov SA, Miyamoto RT, Newman K, Ng D, O’Brien K, Rothenberg S, Schwartzentruber DJ, Singhal V, Tirabosco R, Upton J, Wientroub S, Zackai EH, Hoag K, Whitewood-Neal T, Robey PG, Schwartzberg PL, Darling TN, Tosi LL, Mullikin JC, Biesecker LG (2011) A mosaic activating mutation in AKT1 associated with the Proteus syndrome. N Engl J Med 365:611–619

    CAS  PubMed  Google Scholar 

  149. Livingstone E, Happle R, Hafner C, Piel S, Schadendorf D, Hillen U (2010) SASKIA-Nävus: ein neuer epidermaler Nävus? Poster presented at the 20th Annual Meeting of the Arbeitsgemeinschaft Onkologische Dermatologie, Kiel, Germany, 23–25 September

    Google Scholar 

  150. Llamas-Velasco M, Eguren C, Arranz E, Renedo M, de Argila D, García-Díez A (2010) Linear and whorled nevoid hypermelanosis and Axenfeld-Rieger anomaly: a novel association. Acta Derm Venereol 90:317–318

    PubMed  Google Scholar 

  151. Llamas-Velasco M, Hernandez A, Colmenero I, Torrelo A (2011) Nevus psiloliparus in a child with encephalocraniocutaneous lipomatosis. Actas Dermosifiliogr 102:303–305

    CAS  PubMed  Google Scholar 

  152. Lo LK, Tsai TF, Chen YF, Hung CM, Ko WC (2009) Papulolinear collagenoma with arborizing arrangement: report of a case. Pediatr Dermatol 26:111–112

    PubMed  Google Scholar 

  153. Loffeld A, McLellan NJ, Cole T, Payne SJ, Fricker D, Moss C (2006) Epidermal naevus in Proteus syndrome showing loss of heterozygosity for an inherited PTEN mutation. Br J Dermatol 154:1194–1198

    CAS  PubMed  Google Scholar 

  154. Lookingbill DP, Ladda RL, Cohen C (1984) Generalized epidermolytic hyperkeratosis in the child of a parent with nevus comedonicus. Arch Dermatol 120:223–226

    CAS  PubMed  Google Scholar 

  155. Mabuchi T, Akasaka E, Kondoh A, Umezawa Y, Matsuyama T, Ozawa A (2008) Seborrheic keratosis that follows Blaschko’s lines. J Dermatol 35:301–303

    PubMed  Google Scholar 

  156. Maessen-Visch MB, Hulsmans RF, Hulsmans FJ, Neumann HA (1997) Melanosis naeviformis of Becker and scoliosis: a coincidence? Acta Derm Venereol 77:135–136

    CAS  PubMed  Google Scholar 

  157. Maitra A, Gazdar AF, Moore TO, Moore AY (2002) Loss of heterozygosity analysis of cutaneous melanoma and benign melanocytic nevi: laser capture microdissection demonstrates clonal genetic changes in acquired nevocellular nevi. Hum Pathol 33:191–197

    CAS  PubMed  Google Scholar 

  158. Marchesi L, Naldi L, Di Landro A, Cavalieri d’Oro L, Brevi A, Cainelli T (1992) Segmental lentiginosis with “jentigo” histologic pattern. Am J Dermatopathol 14:323–327

    CAS  PubMed  Google Scholar 

  159. Marriott PJ, Munro DD, Ryan T (1975) Angioma serpiginosum: familial incidence. Br J Dermatol 93:701–706

    Google Scholar 

  160. Marsch WC, Taube KC, Käsemann B (1981) Ein Solitärfall von Ichthyosis hystrix gravior unilateralis: klinische und morphologische Befunde. Z Hautkr 56:1073–1080

    CAS  PubMed  Google Scholar 

  161. Martínez-Glez V, Romanelli V, Mori MA, Gracia R, Segovia M, González-Meneses A, López-Gutierrez JC, Gean E, Martorell L, Lapunzina P (2010) Macrocephaly-capillary malformation: analysis of 13 patients and review of the diagnostic criteria. Am J Med Genet A 152A:3101–3106

    PubMed  Google Scholar 

  162. Maruani A, Khallouf R, Machet MC, Lorette G (2012) Diffuse linear and whorled nevoid hypermelanosis in a newborn. J Pediatr 160:171

    PubMed  Google Scholar 

  163. Masferrer E, Vicente MA, Bassas-Vila J, Rovira C, González-Enseñat MA (2010) Porokeratotic eccrine ostial and dermal duct naevus: report of 10 cases. J Eur Acad Dermatol Venereol 24:847–851

    CAS  PubMed  Google Scholar 

  164. Mehrabi D, Thomas JE, Selim MA, Prose NS (2001) Waxy keratoses of childhood in a segmental distribution. Pediatr Dermatol 18:415–416

    CAS  PubMed  Google Scholar 

  165. Mehregan AH, Pinkus H (1965) Life history of organoid nevi: special reference to nevus sebaceus of Jadassohn. Arch Dermatol 91:574–588

    CAS  PubMed  Google Scholar 

  166. Melnik BC, Vakilzadeh F, Aslanidis C, Schmitz G (2008) Unilateral segmental acneiform naevus: a model disorder towards understanding fibroblast growth factor receptor 2 function in acne? Br J Dermatol 158:1397–1399

    CAS  PubMed  Google Scholar 

  167. Menni S, Betti R, Boccardi D, Gualandri L (2001) Both unilateral naevus achromicus and congenital agminated Spitz naevi in a checkerboard mosaic pattern. Br J Dermatol 144:187–188

    CAS  PubMed  Google Scholar 

  168. Mirzaa GM, Conway RL, Gripp KW, Lerman-Sagie T, Siegel DH, deVries LS, Lev D, Kramer N, Hopkins E, Graham JM Jr, Dobyns WB (2012) Megalencephaly-capillary malformation (MCAP) and megalencephaly-polydactyly-polymicrogyria-hydrocephalus (MPPH) syndromes: two closely related disorders of brain overgrowth and abnormal brain and body morphogenesis. Am J Med Genet A 158A:269–291

    PubMed  Google Scholar 

  169. Moog U, Roelens F, Mortier GR, Sijstermans H, Kelly M, Cox GF, Robson CD, Kimonis VE (2007) Encephalocraniocutaneous lipomatosis accompanied by the formation of bone cysts: harboring clues to pathogenesis? Am J Med Genet A 143A:2973–2980

    PubMed  Google Scholar 

  170. Moore CA, Toriello HV, Abuelo DN, Bull MJ, Curry CJ, Hall BD, Higgins JV, Stevens CA, Twersky S, Weksberg R, Dobyns WB (1997) Macrocephaly-cutis marmorata telangiectatica congenita: a distinct disorder with developmental delay and connective tissue abnormalities. Am J Med Genet 70:67–73

    CAS  PubMed  Google Scholar 

  171. Moss C, Burn J (1990) CHILD + ILVEN = PEN or PENCIL. J Med Genet 27:390–391

    CAS  PubMed  Google Scholar 

  172. Moss C, Savin J (1995) Dermatology and the new genetics. Blackwell Science Ltd, Osney Mead, Oxford

    Google Scholar 

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

    CAS  PubMed  Google Scholar 

  174. Newton-Bishop JA, Chang YM, Iles MM, Taylor JC, Bakker B, Chan M, Leake S, Karpavicius B, Haynes S, Fitzgibbon E, Elliott F, Kanetsky PA, Harland M, Barrett JH, Bishop DT (2010) Melanocytic nevi, nevus genes, and melanoma risk in a large case–control study in the United Kingdom. Cancer Epidemiol Biomarkers Prev 19:2043–2054

    CAS  PubMed  Google Scholar 

  175. Oiso N, Tsuruta D, Imanishi H, Sayasa H, Narita T, Kobayashi H, Ikegami H, Kawada A (2010) Phylloid hypermelanosis and melanocytic nevi with aggregated and disfigured melanosomes: causal relationship between phylloid pigment distribution and chromosome 13 abnormalities. Dermatology 220:169–172

    PubMed  Google Scholar 

  176. Online Mendelian Inheritance in Man (OMIM). Available from: http://www3.ncbi.nlm.nih.gov/Omim/. Accessed 28 Dec 2012

  177. Ousager LB, Bygum A, Hafner C (2012) Identification of a novel S249C FGFR3 mutation in a keratinocytic epidermal nevus syndrome. Br J Dermatol 167:202–204

    CAS  PubMed  Google Scholar 

  178. Paller AS, Syder AJ, Chan YM, Yu QC, Hutton E, Tadini G, Fuchs E (1994) Genetic and clinical mosaicism in a type of epidermal nevus. N Engl J Med 331:1408–1415

    CAS  PubMed  Google Scholar 

  179. Paller AS, van Steensel MA, Rodriguez-Martin M, Sorrell J, Heath C, Crumrine D, van Geel M, Cabrera AN, Elias PM (2011) Pathogenesis-based therapy reverses cutaneous abnormalities in an inherited disorder of distal cholesterol metabolism. J Invest Dermatol 131:2242–2248

    CAS  PubMed  Google Scholar 

  180. Panigrahi I, Bhushan M, Yadav M, Khandelwal N, Singhi P (2012) Macrocephaly-capillary malformation syndrome: three new cases. J Neurol Sci 313:178–181

    PubMed  Google Scholar 

  181. Pinkus H (1965) On the definition of nevi, organ nevi and nevoid tumors. Hautarzt 16:184–190

    CAS  PubMed  Google Scholar 

  182. Plewig G, Christophers E (1975) Nevoid follicular epidermolytic hyperkeratosis. Arch Dermatol 111:223–226

    CAS  PubMed  Google Scholar 

  183. Rahbari H, Cordero AA, Mehregan AH (1974) Linear porokeratosis: a distinctive clinical variant of porokeratosis of Mibelli. Arch Dermatol 109:526–528

    CAS  PubMed  Google Scholar 

  184. Ramolia P, Treadwell P, Haggstrom A (2009) Speckled lentiginous nevus syndrome associated with musculoskeletal abnormalities. Pediatr Dermatol 26:298–301

    PubMed  Google Scholar 

  185. Rawal RC, Goyal P, Rastogi S (2006) Naevoid psoriasis? Unilateral psoriasis? Int J Dermatol 45:1001–1002

    CAS  PubMed  Google Scholar 

  186. Revencu N, Boon LM, Mulliken JB, Enjolras O, Cordisco MR, Burrows PE, Clapuyt P, Hammer F, Dubois J, Baselga E, Brancati F, Carder R, Quintal JM, Dallapiccola B, Fischer G, Frieden IJ, Garzon M, Harper J, Johnson-Patel J, Labreze C, Martorell L, Paltiel HJ, Pohl A, Prendiville J, Quere I, Siegel DH, Valente EM, Van Hagen A, Van Hest L, Vaux KK, Vicente A, Weibel L, Chitayat D, Vikkula M (2008) Parkes Weber syndrome, vein of Galen aneurysmal malformation, and other fast-flow vascular anomalies are caused by RASA1 mutations. Hum Mutat 29:959–965

    CAS  PubMed  Google Scholar 

  187. Rieger E, Kofler R, Borkenstein M, Schwingshandl J, Soyer HP, Kerl H (1994) Melanotic macules following Blaschko’s lines in McCune-Albright syndrome. Br J Dermatol 130:215–220

    CAS  PubMed  Google Scholar 

  188. Rijntjes-Jacobs EG, Lopriore E, Steggerda SJ, Kant SG, Walther FJ (2010) Discordance for Schimmelpenning-Feuerstein-Mims syndrome in monochorionic twins supports the concept of a postzygotic mutation. Am J Med Genet A 152A:2816–2819

    PubMed  Google Scholar 

  189. Rivière JB, Mirzaa GM, O’Roak BJ, Beddaoui M, Alcantara D, Conway RL, St-Onge J, Schwartzentruber JA, Gripp KW, Nikkel SM, Worthylake T, Sullivan CT, Ward TR, Butler HE, Kramer NA, Albrecht B, Armour CM, Armstrong L, Caluseriu O, Cytrynbaum C, Drolet BA, Innes AM, Lauzon JL, Lin AE, Mancini GM, Meschino WS, Reggin JD, Saggar AK, Lerman-Sagie T, Uyanik G, Weksberg R, Zirn B, Beaulieu CL, Majewski J, Bulman DE, O’Driscoll M, Shendure J, Graham JM Jr, Boycott KM, Dobyns WB (2012) De novo germline and postzygotic mutations in AKT3, PIK3R2 and PIK3CA cause a spectrum of related megalencephaly syndromes. Nat Genet 44:934–940

    PubMed  Google Scholar 

  190. Roberts LC, DeVillez RL (1984) Congenital unilateral punctate porokeratosis. Am J Dermatopathol 6:57–61

    CAS  PubMed  Google Scholar 

  191. Romiti R, Romiti N (2004) Papulolinear collagenoma. J Am Acad Dermatol 50:797–798

    PubMed  Google Scholar 

  192. Rompel R, Meyer W, Petres J (1993) Cerebriform intradermal nevus. Hautarzt 44:238–241

    CAS  PubMed  Google Scholar 

  193. Ross AL, Sanchez MI, Grichnik JM (2011) Molecular nevogenesis. Dermatol Res Pract 2011: Article ID 463184

    Google Scholar 

  194. Rübben A, Bogdan I, Grussendorf-Conen EI, Burg G, Böni R (2002) Loss of heterozygosity and microsatellite instability in acquired melanocytic nevi: towards a molecular definition of the dysplastic nevus. Recent Results Cancer Res 160:100–110

    PubMed  Google Scholar 

  195. Ruggieri M, Milone P, Pavone P, Falsaperla R, Polizzi A, Caltabiano R, Fichera M, Gabriele AL, Distefano A, De Pasquale R, Salpietro V, Micali G, Pavone L (2012) Nevus vascularis mixtus (cutaneous vascular twin nevi) associated with intracranial vascular malformation of the Dyke-Davidoff-Masson type in two patients. Am J Med Genet 158A:2870–2880

    PubMed  Google Scholar 

  196. Saldanha G, Purnell D, Fletcher A, Potter L, Gillies A, Pringle JH (2004) High BRAF mutation frequency does not characterize all melanocytic tumor types. Int J Cancer 111:705–710

    CAS  PubMed  Google Scholar 

  197. Santos-Juanes J, Galache C, Curto JR, Carrasco MP, Ribas A, Sánchez del Río J (2002) Acneiform lesions in Becker’s nevus and breast hypoplasia. Int J Dermatol 41:699–700

    PubMed  Google Scholar 

  198. Sapp JC, Turner JT, van de Kamp JM, van Dijk FS, Lowry RB, Biesecker LG (2007) Newly delineated syndrome of congenital lipomatous overgrowth, vascular malformations, and epidermal nevi (CLOVE syndrome) in seven patients. Am J Med Genet A 143A:2944–2958

    PubMed  Google Scholar 

  199. Schauder S, Hanefeld F, Noske UM, Zoll B (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 

  200. Schwindinger WF, Francomano CA, Levine MA (1992) Identification of a mutation in the gene encoding the alpha subunit of the stimulatory G protein of adenylyl cyclase in McCune-Albright syndrome. Proc Natl Acad Sci U S A 89:5152–5156

    CAS  PubMed  Google Scholar 

  201. Shakhova O, Zingg D, Schaefer SM, Hari L, Civenni G, Blunschi J, Claudinot S, Okoniewski M, Beermann F, Mihic-Probst D, Moch H, Wegner M, Dummer R, Barrandon Y, Cinelli P, Sommer L (2012) Sox10 promotes the formation and maintenance of giant congenital naevi and melanoma. Nat Cell Biol 14:882–890

    CAS  PubMed  Google Scholar 

  202. Shear CS, Nyhan WL, Frost P, Weinstein GD (1970) Syndrome of unilateral ectromelia, psoriasis and central nervous system anomalies. In: Bergsma D (ed) The Third Conference on the Clinical Delineation of Birth Defects, Baltimore, Maryland, 1971, Birth defects: original article series. Williams and Wilkins, Baltimore, pp 197–203

    Google Scholar 

  203. Shim JH, Lee DW, Cho BK (1996) A case of Cobb syndrome associated with lymphangioma circumscriptum. Dermatology 193:45–47

    CAS  PubMed  Google Scholar 

  204. Shirley MD, Tang H, Gallione CJ, Baugher JD, Frelin LP, Cohen B, North PE, Marchuk DA, Comi AM, Pevsner J (2013) Sturge-Weber syndrome and port-wine stains caused by somatic mutation in GNAQ. N Engl J Med 368:1971–1979

    CAS  PubMed  Google Scholar 

  205. Steigleder GK, Cortes Cortes A (1971) The activity of sebaceous glands in sebaceous nevi during childhood. Arch Klin Exp Dermatol 239:323–328

    CAS  PubMed  Google Scholar 

  206. Sterry W, Christophers E (1988) Quadrant distribution of dysplastic nevus syndrome. Arch Dermatol 124:926–929

    CAS  PubMed  Google Scholar 

  207. Stoll C, Alembik Y, Grosshans E, de Saint MA (2002) An unusual human mosaic for skin pigmentation. Genet Couns 13:281–287

    CAS  PubMed  Google Scholar 

  208. Sugarman JL (2008) Nevus comedonicus syndrome. In: Ruggieri M, Pascual-Castroviejo I, Di Rocco C (eds) Neurocutaneous diseases: the phacomatoses and hamartoneoplastic syndromes. Springer, Vienna, pp 581–587

    Google Scholar 

  209. Sun BK, Saggini A, Sarin KY, Kim J, Benjamin L, Leboit PE, Khavari PA (2013) Mosaic activating RAS mutations in nevus sebaceus and nevus sebaceus syndrome. J Invest Dermatol 133:824–827

    CAS  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  211. Tekin M, Hişmi BO, Fitoz S, Yalçinkaya F, Ekim M, Kansu A, Ertem M, Deda G, Tutar E, Arsan S, Zhou XP, Pilarski R, Eng C, Akar N (2006) A germline PTEN mutation with manifestations of prenatal onset and verrucous epidermal nevus. Am J Med Genet A 140:1472–1475

    Google Scholar 

  212. Tévar E, Torrelo A, Contreras F, Colmenero I, Zambrano A (2006) Multiple basal cell carcinomas on phacomatosis pigmentokeratotica. Actas Dermosifiliogr 97:518–521

    PubMed  Google Scholar 

  213. Thapa R, Dhar S, Malakar R, Chakrabartty S (2007) Hypomelanosis of Ito-whorled hyperpigmentation combination: a mirror image presentation. Pediatr Dermatol 24:572–573

    PubMed  Google Scholar 

  214. Titeux M, Mendonça V, Décha A, Moreira E, Magina S, Maia A, Lacaze-Buzy L, Mejía JE, Torrão L, Carvalho F, Eça-Guimarães J, Hovnanian A (2009) Keratitis-ichthyosis-deafness syndrome caused by GJB2 maternal mosaicism. J Invest Dermatol 129:776–779

    Google Scholar 

  215. Toriello HV, Mulliken JB (2007) Accurately renaming macrocephaly-cutis marmorata telangiectatica congenita (M-CMTC) as macrocephaly-capillary malformation (M-CM). Am J Med Genet A 143A:3009

    PubMed  Google Scholar 

  216. Torrelo A, Baselga E, Nagore E, Zambrano A, Happle R (2005) Delineation of the various shapes and patterns of nevi. Eur J Dermatol 15:439–450

    PubMed  Google Scholar 

  217. Tran TP, Titus-Ernstoff L, Perry AE, Ernstoff MS, Newsham IF (2002) Alteration of chromosome 9p21 and/or p16 in benign and dysplastic nevi suggests a role in early melanoma progression (United States). Cancer Causes Control 13:675–682

    PubMed  Google Scholar 

  218. Traupe H, Macher E, Hamm H, Happle R (1989) Mutation rate estimates are not compatible with autosomal dominant inheritance of the dysplastic nevus “syndrome”. Am J Med Genet 32:155–157

    CAS  PubMed  Google Scholar 

  219. Uribe P, Wistuba II, Gonzalez S (2009) Allelotyping, microsatellite instability, and BRAF mutation analyses in common and atypical melanocytic nevi and primary cutaneous melanomas. Am J Dermatopathol 31:354–363

    PubMed  Google Scholar 

  220. van Dijk MC, Bernsen MR, Ruiter DJ (2005) Analysis of mutations in B-RAF, N-RAS, and H-RAS genes in the differential diagnosis of Spitz nevus and spitzoid melanoma. Am J Surg Pathol 29:1145–1151

    PubMed  Google Scholar 

  221. Vidaurri-de la Cruz H, Happle R (2006) Two distinct types of speckled lentiginous nevi characterized by macular versus papular speckles. Dermatology 212:53–58

    PubMed  Google Scholar 

  222. Weinstein LS (2006) G(s)alpha mutations in fibrous dysplasia and McCune-Albright syndrome. J Bone Miner Res 21:P120–P124

    CAS  PubMed  Google Scholar 

  223. Weiss T, Mädler U, Oberwittler H, Kahle B, Weiss C, Kübler W (2000) Peripheral vascular malformation (Servelle-Martorell). Circulation 101:E82–E83

    CAS  PubMed  Google Scholar 

  224. Wouters V, Limaye N, Uebelhoer M, Irrthum A, Boon LM, Mulliken JB, Enjolras O, Baselga E, Berg J, Dompmartin A, Ivarsson SA, Kangesu L, Lacassie Y, Murphy J, Teebi AS, Penington A, Rieu P, Vikkula M (2010) Hereditary cutaneomucosal venous malformations are caused by TIE2 mutations with widely variable hyper-phosphorylating effects. Eur J Hum Genet 18:414–420

    CAS  PubMed  Google Scholar 

  225. Wright DR, Frieden IJ, Orlow SJ, Shin HT, Chamlin S, Schaffer JV, Paller AS (2009) The misnomer “macrocephaly-cutis marmorata telangiectatica congenita syndrome”: report of 12 new cases and support for revising the name to macrocephaly-capillary malformations. Arch Dermatol 145:287–293

    PubMed  Google Scholar 

  226. Yap FB (2009) Nevus lipomatosus superficialis. Singapore Med J 50:e161–e162

    CAS  PubMed  Google Scholar 

  227. Yu X, Nagai H, Nishigori C, Horikawa T (2008) Acquired unilateral melanocytic nevi in otherwise normal skin. Dermatology 217:63–65

    PubMed  Google Scholar 

  228. Zietz S, Happle R, Hohenleutner U, Landthaler M (2008) The venous nevus: a distinct vascular malformation suggesting mosaicism. Dermatology 216:31–36

    PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, Freiburg University Medical Center, Freiburg, Germany

    Rudolf Happle

Authors
  1. Rudolf Happle
    View author publications

    You can also search for this author in PubMed Google Scholar

Rights and permissions

Reprints and permissions

Copyright information

© 2014 Springer-Verlag Berlin Heidelberg

About this chapter

Cite this chapter

Happle, R. (2014). Nevi. In: Mosaicism in Human Skin. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-38765-4_7

Download citation

  • DOI: https://doi.org/10.1007/978-3-642-38765-4_7

  • Published:

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-38764-7

  • Online ISBN: 978-3-642-38765-4

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation