Advertisement

Human Genetics

, Volume 70, Issue 3, pp 200–206 | Cite as

Lyonization and the lines of Blaschko

  • R. Happle
Review Articles

Summary

The lines of Blaschko represent a nonrandom developmental pattern of the skin fundamentally differing from the system of dermatomes. Many nevoid skin lesions display an arrangement following these lines. This is a review of case reports providing photographically documented evidence that the lines of Blaschko become manifest in the heterozygous state of various X-linked gene defects such as incontinentia pigmenti, focal dermal hypoplasia, X-linked dominant chondrodysplasia punctata, X-linked hypohidrotic ectodermal dysplasia, and Menkes syndrome. Hence, a causal relationship between lyonization and the lines of Blaschko seems quite obvious. Although it should be borne in mind that other genetic mechanisms such as somatic mutations or chimerism may give rise to the same linear pattern, the datable embryologic event of X-inactivation seems most suitable to explain the origin and nature of the lines of Blaschko. Apparently, in women affected with X-linked skin disorders the lines of Blaschko visualize the clonal proliferation of two functionally different populations of cells during early embryogenesis of the skin. The typical dorsal V-shape and the abdominal S-figure of these lines may result from an interference of the transversal coherent proliferation with the longitudinal growth and flexion of the embryo. In contrast to Blaschko's original assumption, it is now clear that these lines are independent from the metameric structure of the human body. Obviously, they represent a marker of the normal development of human skin. Therefore, a thorough study of the distribution pattern of X-linked skin disorders in women may give us a better insight into the early embryogeny of the human integument.

Keywords

Somatic Mutation Gene Defect Developmental Pattern Heterozygous State Early Embryogenesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Allansmith M, Senz E (1960) Chondrodysplasia congenita punctata (Conradi's disease). Review of literature and report of case with unusual features. Am J Dis Child 100:109–116Google Scholar
  2. Blaschko A (1901) Die Nervenverteilung in der Haut in ihrer Beziehung zu den Erkrankungen der Haut. Braumüller, Wien LeipzigGoogle Scholar
  3. Bloxsom A, Johnston RA (1938) Calcinosis universalis with unusual features. Am J Dis Child 56:103–109Google Scholar
  4. Bodian EL (1966) Skin manifestations of Conradi's disease (chondrodystrophia congenita punctata). Arch Dermatol 94:743–748Google Scholar
  5. Braun-Falco O, Marghescu S (1965) Über eine systematisierte naeviforme Atrophodermie. Arch Klin Exp Dermatol 221:549–565Google Scholar
  6. Carney RG (1976) Incontinentia pigmenti. A world statistical analysis. Arch Dermatol 112:535–542Google Scholar
  7. Cattanach BM, Wolfe HG, Lyon MF (1972) A comparative study of the coast of chimaeric mice and those of heterozygotes for X-linked genes. Genet Res 19:213–228Google Scholar
  8. Champion RH (1975) Focal dermal hypoplasia. Br J Dermatol 93 (Suppl 2):70–71Google Scholar
  9. Cottenot F, Bourgeois-Droin Ch, Wallach D, Guétrot D (1979) Hypoplasie dermique en aires associée à une dysplasie fibreuse des os. Ann Dermatol Venereol 106:167–169Google Scholar
  10. Collie WR, Moore CM, Goka TJ, Howell RR (1978) Pili torti as marker for carriers of Menkes disease. Lancet I:607–608Google Scholar
  11. Curth HO (1949) Follicular atrophoderma and pseudopelade associated with chondrodystrophia calcificans congenita. J Invest Dermatol 13:233–247Google Scholar
  12. Curth HO, Warburton D (1965) The genetics of incontinentia pigmenti. Arch Dermatol 92:229–235Google Scholar
  13. Danks DM, Campbell PE, Stevens BJ, Bayne V, Cartwright E (1972) Menkes's kinky hair syndrome. An inherited defect in copper absorption with widespread effects. Pediatrics 50:188–201Google Scholar
  14. Edidin DV, Esterly NB, Bamzai AK, Fretzin DF (1977) Chondrodysplasia punctata (Conradi-Hünermann syndrome). Arch Dermatol 113:1431–1434Google Scholar
  15. Findley GH, Moores PP (1980) Pigment anomalies of the skin in the human chimacra: Their relation to systematized naevi. Br J Dermatol 103:489–498Google Scholar
  16. Fitzgerald PH, Donald RA, Kirk RL (1979) A true hermaphrodite dispermic chimera with 46,XX and 46,XY karyotypes. Clin Genet 15:89–96Google Scholar
  17. Gordon H, Gordon W (1970) Incontinentia pigmenti: Clinical and genetical studies of two familial cases. Dermatologica 140:150–168Google Scholar
  18. Grüneberg T (1955) Zur Frage der Incontinentia pigmenti (Bloch-Sulzberger). Arch Klin Exp Dermatol 201:218–254Google Scholar
  19. Haber H (1952) The Bloch-Sulzberger syndrome (incontinentia pigmenti). Br J Dermatol 64:129–140Google Scholar
  20. Hässler E, Schallock G (1940) Chondrodystrophia calcificans. Monatsschr Kinderheilkd 82:133–157Google Scholar
  21. Hamilton WJ, Boyd JD, Mossman HW (1964) Human embryology (prenatal development of form and function), 3rd edn. Heffer and Sons, Cambridge, pp 121–122Google Scholar
  22. Happle R (1977) Genetische Bedeutung der Blaschkoschen Linien. Z Hautkr 52:935–944Google Scholar
  23. Happle R (1979) X-linked dominant chondrodysplasia punctata. Review of literature and report of a case. Hum Genet 53:65–73Google Scholar
  24. Happle R, Frosch PJ (1985) Manifestattion of the lines of Blaschko in women heterozygous for X-linked hypohidrotic ectodermal dysplasia. Clin Genet 27:468–471Google Scholar
  25. Happle R, Mathiass HH, Macher E (1977) Sex-linked chondrodysplasia punctata? Clin Genet 11:73–76Google Scholar
  26. Happle R, Phillips RJS, Roessner A, Jünemann G (1983) Homologous genes for X-linked chondrodysplasia punctata in man and mouse. Hum Genet 63:24–27Google Scholar
  27. Happle R, Fuhrmann-Rieger A, Fuhrmann W (1984) Wie verlaufen die Blaschko-Linien am behaarten Kopf? Hautarzt 35:366–369Google Scholar
  28. Hopkins JG, Machacek GF (1941) Incontinentia pigmenti (Bloch-Sulzberger); melanosis corii degenerativa (H. W. Siemens); chromatophore nevus (Naegeli). Arch Dermatol Syph 43:728–731Google Scholar
  29. Howell JB (1965) Nevus angiolipomatosus vs focal dermal hypoplasia. Arch Dermatol 92:238–248Google Scholar
  30. Jancu T, Komlos L, Shabtay F, Elian E, Halbrecht I, Böök JA (1975) Incontinentia pigmenti. Clin Genet 7:103–110Google Scholar
  31. Jackson R (1976) The lines of Blaschko: A review and reconsideration. Observations of the cause of certain unusual linear conditions of the skin. Br J Dermatol 95:349–360Google Scholar
  32. Kerr CB, Wells RS, Cooper KE (1966) Gene effect in carriers of anhidrotic ectodermal dysplasia. J Med Genet 3:169–176Google Scholar
  33. Kleinebrecht J, Degenhardt KH, Grubisic A, Günther E, Svejcar J (1981) Sweat pore counts in ectodermal dysplasias. Hum Genet 57:437–439Google Scholar
  34. Lenz W (1961a) Zur Genetik der Incontinentia pigmenti. Ann Paediatr 196:149–165Google Scholar
  35. Lenz W (1961b) Medizinische Genetik. Eine Einführung in ihre Grundlagen und Probleme. Thieme, Stuttgart, p 89Google Scholar
  36. Lenz W (1975) Half chromatid mutations may explain incontinentia pigmenti in males. Am J Hum Genet 27:690Google Scholar
  37. Lyon MF (1961) Gene action in the X-chromosome of the mouse (Mus musculus L.). Nature 190:372–373Google Scholar
  38. Lyon MF (1972) X-chromosome inactivation and developmental patterns in mammals. Biol Rev 47:1–35Google Scholar
  39. Martin-Scott I (1965) Congenital focal dermal hypoplasia. Br J Dermatol 77:60–62Google Scholar
  40. McKusick VA (1964) On the X chromosome of man. American Institute of Biological Sciences. Washington, p 101Google Scholar
  41. McLaren A (1976) Mammalian chimaeras. Cambridge University Press, Cambridge, pp 52–59, 118–128Google Scholar
  42. Mintz B (1967) Gene control of mammalian pigmentary differentiation, I. Clonal origin of melanocytes. Proc Natl Acad Sci USA 58:344–351Google Scholar
  43. Paltzik RL, Ente G, Penzer PH, Goldblum LM (1982) Conradi-Hünermann disease. Case report and mini-review. Cutis 29:174–180Google Scholar
  44. Partington MW, Marriott PJ, Prentice RSA, Cavaglia A, Simpson NE (1981) Familial cutaneous amyloidosis with systemic manifestations in males. Am J Med Genet 10:65–75Google Scholar
  45. Passarge E, Fries E (1973) X-chromosome inactivation in X-linked hypohidrotic ectodermal dysplasia. Nature (New Biol) 245:58–59Google Scholar
  46. Pfister R (1969) Ein Beitrag zur Klinik der Incontinentia pigmenti (Bloch-Sulzberger). Schweiz Med Wochenschr 99:676–681Google Scholar
  47. Schneidman HM, Snyder AH (1958) Incontinentia pigmenti. Arch Dermatol 77:144Google Scholar
  48. Thiel HJ, Manzke H, Gunschera H (1969) Katarakt bei Chondrodystrophia calcificans connata (Conradi-Hünermann-Syndrom). Klin Monatsbl Augenheilkd 154:536–545Google Scholar
  49. Verger P, Channarond J, Beylot C, Bioulac M (1975) Hypoplasie dermique en aires et ostéopathie striée. Ann Pediatr (Paris) 22:349–354Google Scholar
  50. Volpintesta EJ (1974) Menkes kinky hair syndrome in a black infant. Am J Dis Child 128:244–246Google Scholar
  51. West JD (1975) A theoretical approach to the relation between patch size and clone size in chimaeric tissue. J Theor Biol 50:153–160Google Scholar
  52. Wettke-Schäfer R, Kantner G (1983) X-linked dominant inherited diseases with lethality in hemizygous males. Hum Genet 64:1–23Google Scholar
  53. Willetts GS (1974) Focal dermal hypoplasia. Br J Ophthalmol 58:620–624Google Scholar
  54. Wolpert L, Gingell D (1970) Striping and the pattern of melanocyte cells in chimaeric mice. J Theor Biol 29:147–150Google Scholar
  55. Zuelzer WW, Beattie KM, Reisman LE (1964) Generalized unbalanced mosaicism atributable to dispermy and probable fertilization of a polar body. Am J Hum Genet 16:38–51Google Scholar

Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • R. Happle
    • 1
  1. 1.Department of DermatologyUniversity of MünsterMünsterFederal Republic of Germany

Personalised recommendations