Skip to main content
SpringerLink
Log in

Gender and Genodermatoses

  • Chapter
  • First Online:
Gender and Dermatology

Abstract

Inherited skin disorders that have gender specific expression, are those genodermatoses that involve the sex chromosomes. These include the X-linked genodermatoses (recessive and dominant) and sex chromosome abnormalities. The normal X inactivation (lyonization) which occurs in females and results in functional mosaicism, determines the variable phenotypic expression of the same genetic defect, among genders. In recessive X-linked disorders males are affected, while females may be asymptomatic or present with variable and usually mild phenotype, following a mosaic pattern of distribution. Dominant X-linked disorders are usually lethal in male embryos and are seen almost exclusively in female heterozygotes, usually presenting with Blaschko-linear skin involvement. In this chapter, we will review the various X-linked genodermatoses, as well as the cutaneous features of sex chromosomal abnormalities.

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 219.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 279.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 379.99
Price excludes VAT (USA)
  • Durable hardcover 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. Feramisco JD, Sadreyev RI, Murray ML, Grishin NV, Tsao H. Phenotypic and genotypic analyses of genetic skin disease through the online mendelian inheritance in man (OMIM) database. J Invest Dermatol. 2009;129(11):2628–36.

    Article  CAS  PubMed  Google Scholar 

  2. Lemke JR, Kernland-Lang K, Hörtnagel K, Itin P. Monogenic human skin disorders. Dermatology. 2014;229(2):55–64.

    Article  CAS  PubMed  Google Scholar 

  3. Fine J-D, Eady RA, Bauer EA, Bauer JW, Bruckner-Tuderman L, Heagerty A, et al. The classification of inherited epidermolysis bullosa (EB): report of the third international consensus meeting on diagnosis and classification of EB. J Am Acad Dermatol. 2008;58(6):931–50.

    Article  PubMed  Google Scholar 

  4. Oji V, Tadini G, Akiyama M, Bardon CB, Bodemer C, Bourrat E, et al. Revised nomenclature and classification of inherited ichthyoses: results of the first Ichthyosis consensus conference in Soreze 2009. J Am Acad Dermatol. 2010;63(4):607–41.

    Article  PubMed  Google Scholar 

  5. Lyon MF. X-chromosome inactivation: a repeat hypothesis. Cytogenet Genome Res. 1998;80(1-4):133–7.

    Article  CAS  Google Scholar 

  6. Sun BK, Tsao H. X-chromosome inactivation and skin disease. J Invest Dermatol. 2008;128(12):2753–9.

    Article  CAS  PubMed  Google Scholar 

  7. Wells R, Kerr C. Genetic classification of ichthyosis. Arch Dermatol. 1965;92(1):1–6.

    Article  CAS  PubMed  Google Scholar 

  8. Elias P, Williams M, Maloney M, Bonifas J, Brown B, Grayson S, et al. Stratum corneum lipids in disorders of cornification. Steroid sulfatase and cholesterol sulfate in normal desquamation and the pathogenesis of recessive X-linked ichthyosis. J Clin Invest. 1984;74(4):1414.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Williams ML. Epidermal lipids and scaling diseases of the skin. Semin Dermatol. 1992;11:169.

    CAS  PubMed  Google Scholar 

  10. Bonifas JM, Morley BJ, Oakey RE, Kan YW, Epstein EH. Cloning of a cDNA for steroid sulfatase: frequent occurrence of gene deletions in patients with recessive X chromosome-linked ichthyosis. Proc Natl Acad Sci U S A. 1987;84(24):9248–51.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Reed M, Purohit A, Woo L, Newman SP, Potter BV. Steroid sulfatase: molecular biology, regulation, and inhibition. Endocr Rev. 2005;26(2):171–202.

    Article  CAS  PubMed  Google Scholar 

  12. Siegel DH, Sybert VP. Mosaicism in genetic skin disorders. Pediatr Dermatol. 2006;23(1):87–92.

    Article  PubMed  Google Scholar 

  13. Mevorah B, Frenk E, Müller C, Ropers H. X-linked recessive ichthyosis in three sisters: evidence for homozygosity. Br J Dermatol. 1981;105(6):711–7.

    Article  CAS  PubMed  Google Scholar 

  14. Hazan C, Orlow SJ, Schaffer JV. X-linked recessive ichthyosis. Dermatol Online J. 2005;11(4):12.

    Google Scholar 

  15. Fernandes NF, Janniger CK, Schwartz RA. X-linked ichthyosis: an oculocutaneous genodermatosis. J Am Acad Dermatol. 2010;62(3):480–5.

    Article  PubMed  Google Scholar 

  16. Traupe H, Happle R. Clinical spectrum of steroid sulfatase deficiency: X-linked recessive ichthyosis, birth complications and cryptorchidism. Eur J Pediatr. 1983;140(1):19–21.

    Article  CAS  PubMed  Google Scholar 

  17. Lykkesfeldt G, Lykkesfeldt A, Hoyer H, Skakkebaek N. Steroid sulphatase deficiency associated with testis cancer. Lancet. 1983;322(8365):1456.

    Article  Google Scholar 

  18. Lynch HT, Ozer F, CW MN, Johnson JE, Jampolsky NA. Secondary male hypogonadism and congenital ichthyosis: association of two rare genetic diseases. Am J Hum Genet. 1960;12(4 Pt 1):440.

    CAS  PubMed  PubMed Central  Google Scholar 

  19. Bradshaw K, Carr B. Placental sulfatase deficiency: maternal and fetal expression of steroid sulfatase deficiency and X-linked ichthyosis. Obstet Gynecol Surv. 1986;41(7):401–13.

    CAS  PubMed  Google Scholar 

  20. Liaugaudienė O, Benušienė E, Domarkienė I, Ambrozaitytė L, Kučinskas V. X-linked ichthyosis: differential diagnosis of low maternal oestriol level. J Obstetric Gynecol. 2014;34(8):737–9.

    Article  Google Scholar 

  21. Costagliola C, Fabbrocini G, Illiano G, Scibelli G, Delfino M. Ocular findings in X-linked ichthyosis: a survey on 38 cases. Ophthalmologica. 1991;202(3):152–5.

    Article  CAS  PubMed  Google Scholar 

  22. Fabry J. Ein Beitrag zur Kenntniss der Purpura haemorrhagica nodularis (Purpura papulosa haemorrhagica Hebrae). Arch Dermatol Res. 1898;43(1):187–200.

    Article  Google Scholar 

  23. Anderson W. A case of “Angeio-Keratoma.” Br J Dermatol. 1898;10(4):113–7.

    Article  Google Scholar 

  24. Calhoun DH, Bishop DF, Bernstein HS, Quinn M, Hantzopoulos P, Desnick RJ. Fabry disease: isolation of a cDNA clone encoding human alpha-galactosidase A. Proc Natl Acad Sci U S A. 1985;82(21):7364–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Inoue T, Hattori K, Ihara K, Ishii A, Nakamura K, Hirose S. Newborn screening for Fabry disease in Japan: prevalence and genotypes of Fabry disease in a pilot study. J Hum Genet. 2013;58(8):548–52.

    Article  CAS  PubMed  Google Scholar 

  26. Schiffmann R, Ries M. Fabry disease: a disorder of childhood onset. Pediatr Neurol. 2016;64:10–20.

    Article  PubMed  Google Scholar 

  27. Ries M, Moore DF, Robinson CJ, Tifft CJ, Rosenbaum KN, Brady RO, et al. Quantitative dysmorphology assessment in Fabry disease. Genet Med. 2006;8(2):96–101.

    Article  PubMed  Google Scholar 

  28. Hoffmann B, Schwarz M, Mehta A, Keshav S, Investigators FOSE. Gastrointestinal symptoms in 342 patients with Fabry disease: prevalence and response to enzyme replacement therapy. Clin Gastroenterol Hepatol. 2007;5(12):1447–53.

    Article  PubMed  Google Scholar 

  29. Magage S, Lubanda J-C, Susa Z, Bultas J, Karetova D, Dobrovolný R, et al. Natural history of the respiratory involvement in Anderson–Fabry disease. J Inherit Metab Dis. 2007;30(5):790–9.

    Article  CAS  PubMed  Google Scholar 

  30. Cole A, Lee P, Hughes D, Deegan P, Waldek S, Lachmann R. Depression in adults with Fabry disease: a common and under-diagnosed problem. J Inherit Metab Dis. 2007;30(6):943–51.

    Article  CAS  PubMed  Google Scholar 

  31. Sachdev B, Takenaka T, Teraguchi H, Tei C, Lee P, McKenna W, et al. Prevalence of Anderson-Fabry disease in male patients with late onset hypertrophic cardiomyopathy. Circulation. 2002;105(12):1407–11.

    Article  CAS  PubMed  Google Scholar 

  32. Nakao S, Kodama C, Takenaka T, Tanaka A, Yasumoto Y, Yoshida A, et al. Fabry disease: detection of undiagnosed hemodialysis patients and identification of a “renal variant” phenotype1. Kidney Int. 2003;64(3):801–7.

    Article  PubMed  Google Scholar 

  33. Deegan P, Baehner A, Romero MA, Hughes D, Kampmann C, Beck M. Natural history of Fabry disease in females in the Fabry outcome survey. J Med Genet. 2006;43(4):347–52.

    Article  CAS  PubMed  Google Scholar 

  34. Wang RY, Lelis A, Mirocha J, Wilcox WR. Heterozygous Fabry women are not just carriers, but have a significant burden of disease and impaired quality of life. Genet Med. 2007;9(1):34–45.

    Article  CAS  PubMed  Google Scholar 

  35. Happle R. X-chromosome inactivation: role in skin disease expression. Acta Paediatr. 2006;95(S451):16–23.

    Article  Google Scholar 

  36. Wilcox WR, Oliveira JP, Hopkin RJ, Ortiz A, Banikazemi M, Feldt-Rasmussen U, et al. Females with Fabry disease frequently have major organ involvement: lessons from the Fabry registry. Mol Genet Metab. 2008;93(2):112–28.

    Article  CAS  PubMed  Google Scholar 

  37. Eng CM, Guffon N, Wilcox WR, Germain DP, Lee P, Waldek S, et al. Safety and efficacy of recombinant human α-galactosidase A replacement therapy in Fabry’s disease. N Engl J Med. 2001;345(1):9–16.

    Article  CAS  PubMed  Google Scholar 

  38. Wilcox WR, Banikazemi M, Guffon N, Waldek S, Lee P, Linthorst GE, et al. Long-term safety and efficacy of enzyme replacement therapy for Fabry disease. Am J Hum Genet. 2004;75(1):65–74.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Trzeciak WH, Koczorowski R. Molecular basis of hypohidrotic ectodermal dysplasia: an update. J Appl Genet. 2016;57(1):51–61.

    Article  CAS  PubMed  Google Scholar 

  40. Deshmukh S, Prashanth S. Ectodermal dysplasia: a genetic review. Int J Clin Pediatr Dent. 2012;5(3):197–202.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Fete M, Hermann J, Behrens J, Huttner KM. X-linked hypohidrotic ectodermal dysplasia (XLHED): clinical and diagnostic insights from an international patient registry. Am J Med Genet A. 2014;164(10):2437–42.

    Article  Google Scholar 

  42. Freire-Maia N, Pinheiro M. Carrier detection in Christ-Siemens-Touraine syndrome (X-linked hypohidrotic ectodermal dysplasia). Am J Hum Genet. 1982;34(4):672.

    CAS  PubMed  PubMed Central  Google Scholar 

  43. Cambiaghi S, Restano L, Pääkkönen K, Caputo R, Kere J. Clinical findings in mosaic carriers of hypohidrotic ectodermal dysplasia. Arch Dermatol. 2000;136(2):217–24.

    Article  CAS  PubMed  Google Scholar 

  44. Clarke A, Phillips D, Brown R, Harper PS. Clinical aspects of X-linked hypohidrotic ectodermal dysplasia. Arch Dis Child. 1987;62(10):989–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Visinoni AF, Lisboa-Costa T, Pagnan NA, Chautard-Freire-Maia EA. Ectodermal dysplasias: clinical and molecular review. Am J Med Genet A. 2009;149(9):1980–2002.

    Article  CAS  Google Scholar 

  46. Kaler SG. Metabolic and molecular bases of Menkes disease and occipital horn syndrome. Pediatr Dev Pathol. 1998;1(1):85–98.

    Article  CAS  PubMed  Google Scholar 

  47. Vulpe C, Levinson B, Whitney S, Packman S, Gitschier J. Isolation of a candidate gene for Menkes disease and evidence that it encodes a copper-transporting ATPase. Nat Genet. 1993;3(1):7–13.

    Article  CAS  PubMed  Google Scholar 

  48. Kaler SG. Inborn errors of copper metabolism. Handb Clin Neurol. 2013;113:1745.

    Article  PubMed  PubMed Central  Google Scholar 

  49. Kaler SG. ATP7A-related copper transport disorders. 2010.

    Google Scholar 

  50. Nadal D, Baerlocher K. Menkes’ disease: long-term treatment with copper and D-penicillamine. Eur J Pediatr. 1988;147(6):621–5.

    Article  CAS  PubMed  Google Scholar 

  51. Moore CM, Howell RR. Ectodermal manifestations in Menkes disease. Clin Genet. 1985;28(6):532–40.

    Article  CAS  PubMed  Google Scholar 

  52. Taylor C, Green S. Menkes’ syndrome (Trichopoliodystrophy): use of scanning electron-microscope in diagnosis and carrier identification. Dev Med Child Neurol. 1981;23(3):361–8.

    Article  CAS  PubMed  Google Scholar 

  53. Craiu D, Kaler S, Craiu M. Role of optic microscopy for early diagnosis of Menkes. Romanian J Morphol Embryol. 2014;55(3):953–6.

    Google Scholar 

  54. Smpokou P, Samanta M, Berry GT, Hecht L, Engle EC, Lichter-Konecki U. Menkes disease in affected females: the clinical disease spectrum. Am J Med Genet A. 2015;167(2):417–20.

    Article  CAS  Google Scholar 

  55. Desai V, Donsante A, Swoboda KJ, Martensen M, Thompson J, Kaler S. Favorably skewed X-inactivation accounts for neurological sparing in female carriers of Menkes disease. Clin Genet. 2011;79(2):176–82.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Kaler SG, Holmes CS, Goldstein DS, Tang J, Godwin SC, Donsante A, et al. Neonatal diagnosis and treatment of Menkes disease. N Engl J Med. 2008;358(6):605–14.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  57. Kaler SG, Liew CJ, Donsante A, Hicks JD, Sato S, Greenfield JC. Molecular correlates of epilepsy in early diagnosed and treated Menkes disease. J Inherit Metab Dis. 2010;33(5):583–9.

    Article  PubMed  PubMed Central  Google Scholar 

  58. Derry JM, Gormally E, Means GD, Zhao W, Meindl A, Kelley RI, et al. Mutations in a Δ8-Δ7 sterol isomerase in the tattered mouse and X-linked dominant chondrodysplasia punctata. Nat Genet. 1999;22(3):286–90.

    Article  CAS  PubMed  Google Scholar 

  59. Braverman N, Lin P, Moebius FF, Obie C, Moser A, Glossmann H, et al. Mutations in the gene encoding 3β-hydroxysteroid-Δ 8, Δ7-isomerase cause X-linked dominant Conradi-Hünermann syndrome. Nat Genet. 1999;22(3):291–4.

    Article  CAS  PubMed  Google Scholar 

  60. Happle R. X-linked dominant chondrodysplasia punctata. Hum Genet. 1979;53(1):65–73.

    Article  CAS  PubMed  Google Scholar 

  61. Happle R, Frosch P. Manifestation of the lines of Blaschko in women heterozygous for X-linked hypohidrotic ectodermal dysplasia. Clin Genet. 1985;27(5):468–71.

    Article  CAS  PubMed  Google Scholar 

  62. Aughton DJ, Kelley RI, Metzenberg A, Pureza V, Pauli RM. X-linked dominant chondrodysplasia punctata (CDPX2) caused by single gene mosaicism in a male. Am J Med Genet A. 2003;116(3):255–60.

    Article  Google Scholar 

  63. Tan C, Haverfield E, Dempsey M, Kratz L, Descartes M, Powell B. X-linked dominant chondrodysplasia punctata and EBP mutations in males. Poster session. American College of Medical Genetics Annual Clinical Genetics Meeting, Albuquerque, NM; 2010.

    Google Scholar 

  64. Sutphen R, Amar MJ, Kousseff BG, Toomey KE. XXY male with X-linked dominant chondrodysplasia punctata (Happle syndrome). Am J Med Genet. 1995;57(3):489–92.

    Article  CAS  PubMed  Google Scholar 

  65. Crovato F, Rebora A. Acute skin manifestations of Conradi-Huenermann syndrome in a male adult. Arch Dermatol. 1985;121(8):1064–5.

    Article  CAS  PubMed  Google Scholar 

  66. De Raeve L, Song M, De Dobbeleer G, Spehl M, Regemorter V. Lethal course of X-linked dominant chondrodysplasia punctata in a male newborn. Dermatology. 1989;178(3):167–70.

    Article  Google Scholar 

  67. Tronnier M, Froster-Iskenius U, Schmeller W, Happle R, Wolff H. X-chromosome dominant chondrodysplasia punctata (Happle) in a boy. Hautarzt. 1992;43(4):221–5.

    Google Scholar 

  68. Omobono E, Goetsch W. Chondrodysplasia punctata (the Conradi-Hunermann syndrome). A clinical case report and review of the literature. Minerva Pediatr. 1993;45(3):117–21.

    Google Scholar 

  69. Dempsey MA, Tan C, Herman GE. Chondrodysplasia punctata 2, X-linked. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews. Seattle: University of Washington; 2011.

    Google Scholar 

  70. Cañueto J, Girós M, Ciria S, Pi-Castán G, Artigas M, García-Dorado J, et al. Clinical, molecular and biochemical characterization of nine Spanish families with Conradi–Hünermann–Happle syndrome: new insights into X-linked dominant chondrodysplasia punctata with a comprehensive review of the literature. Br J Dermatol. 2012;166(4):830–8.

    Article  CAS  PubMed  Google Scholar 

  71. Happle R. Cataracts as a marker of genetic heterogeneity in chondrodysplasia punctata. Clin Genet. 1981;19(1):64–6.

    Article  CAS  PubMed  Google Scholar 

  72. Herman GE, Kelley RI, Pureza V, Smith D, Kopacz K, Pitt J, et al. Characterization of mutations in 22 females with X-linked dominant chondrodysplasia punctata (Happle syndrome). Genet Med. 2002;4(6):434–8.

    Article  CAS  PubMed  Google Scholar 

  73. Milunsky JM, Maher TA, Metzenberg AB. Molecular, biochemical, and phenotypic analysis of a hemizygous male with a severe atypical phenotype for X-linked dominant Conradi-Hunermann-Happle syndrome and a mutation in EBP. Am J Med Genet A. 2003;116(3):249–54.

    Article  Google Scholar 

  74. Furtado LV, Bayrak-Toydemir P, Hulinsky B, Damjanovich K, Carey JC, Rope AF. A novel X-linked multiple congenital anomaly syndrome associated with an EBP mutation. Am J Med Genet A. 2010;152(11):2838–44.

    Article  CAS  Google Scholar 

  75. Haber H. The Bloch-Sulzberger syndrome (Incontinentia Pigmenti). Br J Dermatol. 1952;64(4):129–40.

    Article  CAS  PubMed  Google Scholar 

  76. Fusco F, Bardaro T, Fimiani G, Mercadante V, Miano MG, Falco G, et al. Molecular analysis of the genetic defect in a large cohort of IP patients and identification of novel NEMO mutations interfering with NF-κB activation. Hum Mol Genet. 2004;13(16):1763–73.

    Article  CAS  PubMed  Google Scholar 

  77. Smahi A, Courtois G, Vabres P, Yamaoka S, Heuertz S, Munnich A, et al. Genomic rearrangement in NEMO impairs NF-κB activation and is a cause of incontinentia pigmenti. Nature. 2000;405(6785):466–72.

    Article  CAS  PubMed  Google Scholar 

  78. Kaufman CK, Fuchs E. It’s got you covered Nf-κb in the epidermis. J Cell Biol. 2000;149(5):999–1004.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  79. Zonana J, Elder ME, Schneider LC, Orlow SJ, Moss C, Golabi M, et al. A novel X-linked disorder of immune deficiency and hypohidrotic ectodermal dysplasia is allelic to incontinentia pigmenti and due to mutations in IKK-gamma (NEMO). Am J Hum Genet. 2000;67(6):1555–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  80. Fusco F, Pescatore A, Bal E, Ghoul A, Paciolla M, Lioi MB, et al. Alterations of the IKBKG locus and diseases: an update and a report of 13 novel mutations. Hum Mutat. 2008;29(5):595–604.

    Article  CAS  PubMed  Google Scholar 

  81. Scheuerle AE. Male cases of incontinentia pigmenti: case report and review. Am J Med Genet. 1998;77(3):201–18.

    Article  CAS  PubMed  Google Scholar 

  82. Fusco F, Fimiani G, Tadini G, Ursini MV. Clinical diagnosis of incontinentia pigmenti in a cohort of male patients. J Am Acad Dermatol. 2007;56(2):264–7.

    Article  PubMed  Google Scholar 

  83. International IP Consortium. Survival of male patients with incontinentia pigmenti carrying a lethal mutation can be explained by somatic mosaicism or Klinefelter syndrome. Am J Hum Genet. 2001;69(6):1210–7.

    Article  Google Scholar 

  84. Pacheco TR, Levy M, Collyer JC, de Parra NP, Parra CA, Garay M, et al. Incontinentia pigmenti in male patients. J Am Acad Dermatol. 2006;55(2):251–5.

    Article  PubMed  Google Scholar 

  85. Hadj-Rabia S, Froidevaux D, Bodak N, Hamel-Teillac D, Smahi A, Touil Y, et al. Clinical study of 40 cases of incontinentia pigmenti. Arch Dermatol. 2003;139(9):1163–70.

    Article  PubMed  Google Scholar 

  86. Landy S, Donnai D. Incontinentia pigmenti (Bloch-Sulzberger syndrome). J Med Genet. 1993;30(1):53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Badgwell A, Iglesias A, Emmerich S, Willner J. The natural history of incontinentia pigmenti as reported by 198 affected individuals. Abstract 38. Nashville, TN: American College of Medical Genetics Annual Meeting; 2007.

    Google Scholar 

  88. Swinney CC, Han DP, Karth PA. Incontinentia pigmenti: a comprehensive review and update. Ophthalmic Surg Lasers Imaging Retina. 2015;46(6):650–7.

    Article  PubMed  Google Scholar 

  89. Watzke RC, Stevens TS, Carney RG. Retinal vascular changes of incontinentia pigmenti. Arch Ophthalmol. 1976;94(5):743–6.

    Article  CAS  PubMed  Google Scholar 

  90. Francois J. Incontinentia pigmenti (Bloch-Sulzberger syndrome) and retinal changes. Br J Ophthalmol. 1984;68(1):19–25.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  91. Goldberg MF, Custis PH. Retinal and other manifestations of incontinentia pigmenti (Bloch-Sulzberger syndrome). Ophthalmology. 1993;100(11):1645–54.

    Article  CAS  PubMed  Google Scholar 

  92. Rosenfeld SI, Smith ME. Ocular findings in incontinentia pigmenti. Ophthalmology. 1985;92(4):543–6.

    Article  CAS  PubMed  Google Scholar 

  93. Holmström G, Thoren K. Ocular manifestations of incontinentia pigmenti. Acta Ophthalmol Scand. 2000;78(3):348–53.

    Article  PubMed  Google Scholar 

  94. Meuwissen ME, Mancini GM. Neurological findings in incontinentia pigmenti; a review. Eur J Med Genet. 2012;55(5):323–31.

    Article  PubMed  Google Scholar 

  95. Minić S, Trpinac D, Obradović M. Incontinentia pigmenti diagnostic criteria update. Clin Genet. 2014;85(6):536–42.

    Article  PubMed  Google Scholar 

  96. Hayes IM, Varigos G, Upjohn EJ, Orchard DC, Penny DJ, Savarirayan R. Unilateral acheiria and fatal primary pulmonary hypertension in a girl with incontinentia pigmenti. Am J Med Genet A. 2005;135(3):302–3.

    Article  PubMed  Google Scholar 

  97. Brown C. Incontinentia pigmenti: the development of pseudoglioma. Br J Ophthalmol. 1988;72(6):452–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  98. Roberts WM, Jenkins JJ, Moorhead EL, Douglass EC. Incontinentia pigmenti, a chromosomal instability syndrome, is associated with childhood malignancy. Cancer. 1988;62(11):2370–2.

    Article  CAS  PubMed  Google Scholar 

  99. Scheuerle AE, Ursini MV. Incontinentia pigmenti. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, LJH B, Bird TD, Ledbetter N, Mefford HC, RJH S, Stephens K, editors. GeneReviews. Seattle: University of Washington; 2015.

    Google Scholar 

  100. Bree AF, Grange DK, Hicks MJ, Goltz RW. Dermatologic findings of focal dermal hypoplasia (Goltz syndrome). Am J Med Genet C Semin Med Genet. 2016;172C:44.

    Article  CAS  PubMed  Google Scholar 

  101. Goltz RW, Peterson WC, Gorlin RJ, Ravits HG. Focal dermal hypoplasia. Arch Dermatol. 1962;86(6):708–17.

    Article  CAS  PubMed  Google Scholar 

  102. Holden JD, Akers WA. Goltz’s syndrome: focal dermal hypoplasia: a combined mesoectodermal dysplasia. Am J Dis Child. 1967;114(3):292–300.

    Article  CAS  PubMed  Google Scholar 

  103. Grzeschik K-H, Bornholdt D, Oeffner F, König A, del Carmen Boente M, Enders H, et al. Deficiency of PORCN, a regulator of Wnt signaling, is associated with focal dermal hypoplasia. Nat Genet. 2007;39(7):833–5.

    Article  CAS  PubMed  Google Scholar 

  104. Wang X, Sutton VR, Peraza-Llanes JO, Yu Z, Rosetta R, Kou Y-C, et al. Mutations in X-linked PORCN, a putative regulator of Wnt signaling, cause focal dermal hypoplasia. Nat Genet. 2007;39(7):836–8.

    Article  CAS  PubMed  Google Scholar 

  105. Proffitt KD, Virshup DM. Precise regulation of porcupine activity is required for physiological Wnt signaling. J Biol Chem. 2012;287(41):34167–78.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  106. Clevers H, Nusse R. Wnt/β-catenin signaling and disease. Cell. 2012;149(6):1192–205.

    Article  CAS  PubMed  Google Scholar 

  107. Molho-Pessach V, Schaffer JV. Blaschko lines and other patterns of cutaneous mosaicism. Clin Dermatol. 2011;29(2):205–25.

    Article  PubMed  Google Scholar 

  108. Wechsler MA, Papa CM, Haberman F, Marion RW. Variable expression in focal dermal hypoplasia: an example of differential X-chromosome inactivation. Am J Dis Child. 1988;142(3):297–300.

    Article  CAS  PubMed  Google Scholar 

  109. Paller AS. Wnt signaling in focal dermal hypoplasia. Nat Genet. 2007;39(7):820–1.

    Article  CAS  PubMed  Google Scholar 

  110. Barrott JJ, Cash GM, Smith AP, Barrow JR, Murtaugh LC. Deletion of mouse Porcn blocks Wnt ligand secretion and reveals an ectodermal etiology of human focal dermal hypoplasia/Goltz syndrome. Proc Natl Acad Sci U S A. 2011;108(31):12752–7.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  111. Bornholdt D, Oeffner F, König A, Happle R, Alanay Y, Ascherman J, et al. PORCN mutations in focal dermal hypoplasia: coping with lethality. Hum Mutat. 2009;30(5):E618–E28.

    Article  PubMed  Google Scholar 

  112. Sutton VR, Van den Veyver IB. Focal dermal hypoplasia. In: Pagon RA, Adam MP, Ardinger HH, Wallace SE, Amemiya A, Bean LJH, Bird TD, Ledbetter N, Mefford HC, Smith RJH, Stephens K, editors. GeneReviews. Seattle: University of Washington; 2013.

    Google Scholar 

  113. Fete TJ, Fete M. International research symposium on Goltz syndrome. Am J Med Genet C Semin Med Genet. 2016;172C:3.

    Article  PubMed  Google Scholar 

  114. Bostwick B, Fang P, Patel A, Sutton VR. Phenotypic and molecular characterization of focal dermal hypoplasia in 18 individuals. Am J Med Genet C Semin Med Genet. 2016;172C:9.

    Article  CAS  PubMed  Google Scholar 

  115. Gisseman JD, Herce HH. Ophthalmologic manifestations of focal dermal hypoplasia (Goltz syndrome): a case series of 18 patients. Am J Med Genet C Semin Med Genet. 2016;172C:59.

    Article  CAS  PubMed  Google Scholar 

  116. Nagalo K, Laberge J, Nguyen V, Laberge-Caouette L, Turgeon J. Focal dermal hypoplasia (Goltz syndrome) in the neonate: report of a case presenting with cleft lip and palate. Arch Pediatr. 2012;19(2):160–2.

    Google Scholar 

  117. Smigiel R, Jakubiak A, Lombardi MP, Jaworski W, Slezak R, Patkowski D, et al. Co-occurrence of severe Goltz-Gorlin syndrome and pentalogy of Cantrell - case report and review of the literature. Am J Med Genet A. 2011;155A(5):1102–5.

    Article  CAS  PubMed  Google Scholar 

  118. Lombardi MP, Bulk S, Celli J, Lampe A, Gabbett MT, Ousager LB, et al. Mutation update for the PORCN gene. Hum Mutat. 2011;32(7):723–8.

    Article  CAS  PubMed  Google Scholar 

  119. Van Assche E, Bonduelle M, Tournaye H, Joris H, Verheyen G, Devroey P, et al. Cytogenetics of infertile men. Hum Reprod. 1996;11(Suppl 4):1–26.

    Article  PubMed  Google Scholar 

  120. Groth KA, Skakkebæk A, Høst C, Gravholt CH, Bojesen A. Klinefelter syndrome—a clinical update. J Clin Endocrinol Metab. 2012;98(1):20–30.

    Article  CAS  PubMed  Google Scholar 

  121. Klinefelter HF Jr, Reifenstein EC Jr, Albright F Jr. Syndrome characterized by gynecomastia, aspermatogenesis without A-Leydigism, and increased excretion of follicle-stimulating hormone 1. J Clin Endocrinol Metab. 1942;2(11):615–27.

    Article  CAS  Google Scholar 

  122. Jacobs PA. A case of human intersexuality having a possible XXY sexdetermining mechanism. Nature. 1959;183:302–3.

    Article  CAS  PubMed  Google Scholar 

  123. Bonomi M, Rochira V, Pasquali D, Balercia G, Jannini E, Ferlin A. Klinefelter syndrome (KS): genetics, clinical phenotype and hypogonadism. J Endocrinol Investig. 2017;40:123–34.

    Article  CAS  Google Scholar 

  124. Aksglaede L, Link K, Giwercman A, Jørgensen N, Skakkebaek NE, Juul A. 47, XXY Klinefelter syndrome: clinical characteristics and age-specific recommendations for medical management. Am J Med Genet C Semin Med Genet. 2013;163C:55.

    Article  PubMed  Google Scholar 

  125. Bojesen A, Gravholt CH. Klinefelter syndrome in clinical practice. Nat Clin Pract Urol. 2007;4(4):192–204.

    Article  PubMed  Google Scholar 

  126. Campbell W, Newton M, Price W. Hypostatic leg ulceration and Klinefelter’s syndrome. J Intelect Disabil Res. 1980;24(2):115–7.

    Article  CAS  Google Scholar 

  127. Zollner TM, Veraart J, Wolter M, Hesse S, Villemur B, Wenke A, et al. Leg ulcers in Klinefelter’s syndrome–further evidence for an involvement of plasminogen activator inhibitor-1. Br J Dermatol. 1997;136(3):341–4.

    Article  CAS  PubMed  Google Scholar 

  128. Shanmugam VK, Tsagaris KC, Attinger CE. Leg ulcers associated with Klinefelter’s syndrome: a case report and review of the literature. Int Wound J. 2012;9(1):104–7.

    Article  PubMed  Google Scholar 

  129. De Morentin HM, Dodiuk-Gad RP, Brenner S. Klinefelter’s syndrome presenting with leg ulcers. Skinmed. 2004;3(5):274–8.

    Article  PubMed  Google Scholar 

  130. Villemur B, Truche H, Pernod G, De Angelis M, Beani J, Halimi S, et al. Leg ulcer and Klinefelter syndrome. J Mal Vasc. 1994;20(3):215–8.

    Google Scholar 

  131. Stochholm K, Juul S, Juel K, Naeraa RW, Højbjerg Gravholt C. Prevalence, incidence, diagnostic delay, and mortality in Turner syndrome. J Clin Endocrinol Metab. 2006;91(10):3897–902.

    Article  CAS  PubMed  Google Scholar 

  132. Turner HH. A syndrome of infantilism, congenital webbed neck, and cubitus valgus 1. Endocrinologist. 1938;23(5):566–74.

    Article  Google Scholar 

  133. Bondy CA. Care of girls and women with Turner syndrome: a guideline of the Turner Syndrome Study Group. J Clin Endocrinol Metab. 2007;92(1):10–25.

    Article  CAS  PubMed  Google Scholar 

  134. Ford CE, Jones KW, Polani PE, De Almeida J, Briggs JH. A sex-chromosome anomaly in a case of gonadal dysgenesis (Turner’s syndrome). Lancet. 1959;273(7075):711–3.

    Article  Google Scholar 

  135. Lowenstein EJ, Kim KH, Glick SA. Turner’s syndrome in dermatology. J Am Acad Dermatol. 2004;50(5):767–76.

    Article  PubMed  Google Scholar 

  136. Robinson W, Binkert F, Bernasconi F, Lorda-Sanchez I, Werder E, Schinzel A. Molecular studies of chromosomal mosaicism: relative frequency of chromosome gain or loss and possible role of cell selection. Am J Hum Genet. 1995;56(2):444.

    CAS  PubMed  PubMed Central  Google Scholar 

  137. Fernández-García R, García-Doval S, Costoya S, Pasaro E. Analysis of sex chromosome aneuploidy in 41 patients with Turner syndrome: a study of ‘hidden’ mosaicism. Clin Genet. 2000;58(3):201–8.

    Article  PubMed  Google Scholar 

  138. Hassold T, Pettay D, Robinson A, Uchida I. Molecular studies of parental origin and mosaicism in 45, X conceptuses. Hum Genet. 1992;89(6):647–52.

    Article  CAS  PubMed  Google Scholar 

  139. Rao E, Weiss B, Fukami M, Rump A, Niesler B, Mertz A, et al. Pseudoautosomal deletions encompassing a novel homeobox gene cause growth failure in idiopathic short stature and Turner syndrome. Nat Genet. 1997;16(1):54–63.

    Article  CAS  PubMed  Google Scholar 

  140. Ferguson-Smith MA. Karyotype-phenotype correlations in gonadal dysgenesis and their bearing on the pathogenesis of malformations. J Med Genet. 1965;2(2):142.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  141. Berdahl LD, Wenstrom KD, Hanson JW. Web neck anomaly and its association with congenital heart disease. Am J Med Genet A. 1995;56(3):304–7.

    Article  CAS  Google Scholar 

  142. Brady AF, Patton MA. Web-neck anomaly and its association with congenital heart disease. Am J Med Genet. 1996;64(4):605.

    Article  CAS  PubMed  Google Scholar 

  143. Becker B, Jospe N, Goldsmith LA. Melanocytic nevi in Turner syndrome. Pediatr Dermatol. 1994;11(2):120–4.

    Article  CAS  PubMed  Google Scholar 

  144. Gibbs P, Brady BM, Gonzalez R, Robinson WA. Nevi and melanoma: lessons from Turner’s syndrome. Dermatology. 2001;202(1):1–3.

    Article  CAS  PubMed  Google Scholar 

  145. Zvulunov A, Wyatt D, Laud P, Esterly N. Influence of genetic and environmental factors on melanocytic naevi: a lesson from Turner’s syndrome. Br J Dermatol. 1998;138(6):993–7.

    Article  CAS  PubMed  Google Scholar 

  146. Schoemaker MJ, Swerdlow AJ, Higgins CD, Wright AF, Jacobs PA. Cancer incidence in women with Turner syndrome in Great Britain: a national cohort study. Lancet Oncol. 2008;9(3):239–46.

    Article  PubMed  Google Scholar 

  147. Lemli L, Smith DW. The XO syndrome: a study of the differentiated phenotype in 25 patients. J Pediatr. 1963;63(4):577–88.

    Article  CAS  PubMed  Google Scholar 

  148. Smith DW, Hanson JW. Asynchronous growth of scalp hair in XO Turner syndrome. J Pediatr. 1975;87(4):659–60.

    Article  CAS  PubMed  Google Scholar 

  149. Kannan TP, Azman BZ, Ahmad Tarmizi AB, Suhaida MA, Siti Mariam I, Ravindran A, et al. Turner syndrome diagnosed in northeastern Malaysia. Singap Med J. 2008;49(5):400–4.

    CAS  Google Scholar 

  150. Rosina P, Segalla G, Magnanini M, Chieregato C, Barba A. Turner’s syndrome associated with psoriasis and alopecia areata. J Eur Acad Dermatol Venereol. 2003;17(1):50–2.

    Article  CAS  PubMed  Google Scholar 

  151. Polani P. Turner’s syndrome and allied conditions: clinical features and chromosome abnormalities. Br Med Bull. 1961;17(3):200–5.

    Article  CAS  PubMed  Google Scholar 

  152. Larizza D, Calcaterra V, Martinetti M. Autoimmune stigmata in Turner syndrome: when lacks an X chromosome. J Autoimmun. 2009;33(1):25–30.

    Article  CAS  PubMed  Google Scholar 

  153. Gravholt CH. Epidemiological, endocrine and metabolic features in Turner syndrome. Eur J Endocrinol. 2004;151(6):657–87.

    Article  CAS  PubMed  Google Scholar 

  154. Larralde M, Gardner SS, Torrado MV, Fernhoff PM, Muñoz AES, Spraker MK, et al. Lymphedema as a postulated cause of cutis verticis gyrata in Turner syndrome. Pediatr Dermatol. 1998;15(1):18–22.

    Article  CAS  PubMed  Google Scholar 

  155. Bello-Quintero CE, Gonzalez ME, Alvarez-Connelly E. Halo nevi in Turner syndrome. Pediatr Dermatol. 2010;27(4):368–9.

    Article  PubMed  Google Scholar 

  156. Brazzelli V, Larizza D, Martinetti M, Martinoli S, Calcaterra V, De Silvestri A, et al. Halo nevus, rather than vitiligo, is a typical dermatologic finding of Turner’s syndrome: clinical, genetic, and immunogenetic study in 72 patients. J Am Acad Dermatol. 2004;51(3):354–8.

    Article  PubMed  Google Scholar 

  157. Handler MZ, Derrick KM, Lutz RE, Morrell DS, Davenport ML, Armstrong AW. Prevalence of pilomatricoma in Turner syndrome: findings from a multicenter study. JAMA Dermatol. 2013;149(5):559–64.

    Article  CAS  PubMed  Google Scholar 

  158. Paller AS, Esterly NB, Charrow J, Cahan FM. Pedal hemangiomas in Turner syndrome. J Pediatr. 1983;103(1):87–8.

    Article  CAS  PubMed  Google Scholar 

  159. Nehal KS, PeBenito R, Orlow SJ. Analysis of 54 cases of hypopigmentation and hyperpigmentation along the lines of Blaschko. Arch Dermatol. 1996;132(10):1167–70.

    Article  CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Dermatology, Hadassah-Hebrew University Medical Center, Jerusalem, Israel

    Sivan Sheffer Levi & Vered Molho-Pessach

Authors
  1. Sivan Sheffer Levi
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Vered Molho-Pessach
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Tel Aviv University, Tel Aviv, Israel

    Ethel Tur

  2. Department of Dermatology, UCSF Medical Center, San Francisco, California, USA

    Howard I. Maibach

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer International Publishing AG, part of Springer Nature

About this chapter

Check for updates. Verify currency and authenticity via CrossMark

Cite this chapter

Levi, S.S., Molho-Pessach, V. (2018). Gender and Genodermatoses. In: Tur, E., Maibach, H. (eds) Gender and Dermatology. Springer, Cham. https://doi.org/10.1007/978-3-319-72156-9_9

Download citation

  • DOI: https://doi.org/10.1007/978-3-319-72156-9_9

  • Published:

  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-72155-2

  • Online ISBN: 978-3-319-72156-9

  • eBook Packages: MedicineMedicine (R0)

Publish with us

Policies and ethics

Search

Navigation