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Ectodermal Dysplasia Skin Fragility Syndrome

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Blistering Diseases

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Abstract

Ectodermal dysplasia skin fragility (EDSF) syndrome results from loss-of-function mutations on both alleles of the PKP1 gene encoding plakophilin 1. The syndrome is also known as plakophilin 1-deficiency or epidermolysus bullosa simplex-plakophilin 1. This autosomal recessive disorder represents the first example of an inherited disorder of desmosome cell-cell junctions in humans. Loss of PKP1 expression leads to skin erosions and crusting, notably with perioral fissuring as well as palmoplantar hyperkeratosis with painful cracking of the skin. Other more variable but prototypic features of EDSF syndrome include growth delay, hypotrichosis or alopecia, and nail dystrophy. Unlike some other genetic diseases of desmosomes, there are no cardiac abnormalities. EDSF syndrome is classified as a suprabasal form of epidermolysis bullosa simplex, and thus far, there have been approximately 12 published cases. This chapter reviews the clinical, structural and molecular pathology of this desmosomal genodermatosis.

Funding

The author acknowledges financial support from the Department of Health via the National Institute for Health Research (NIHR) Comprehensive Biomedical Research Centre award to Guy’s and St. Thomas’ NHS Foundation Trust in partnership with King’s College London and King’s College Hospital NHS Foundation Trust.

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Abbreviations

PKP1:

Plakophilin 1

References

  1. McGrath JA, McMillan JR, Shemanko CS, et al. Mutations in the plakophilin 1 gene result in ectodermal dysplasia/skin fragility syndrome. Nat Genet. 1997;7:241–4.

    Google Scholar 

  2. Green KJ, Simpson CL. Desmosomes: new perspectives on a classic. J Invest Dermatol. 2007;127:2499–515.

    Article  CAS  PubMed  Google Scholar 

  3. Petrof G, Mellerio JE, McGrath JA. Desmosomal genodermatoses. Br J Dermatol. 2012;166:36–45.

    Article  CAS  PubMed  Google Scholar 

  4. Brooke MA, Nitoiu D, Kelsell DP. Cell-cell connectivity: desmosomes and disease. J Pathol. 2012;226:158–71.

    Article  CAS  PubMed  Google Scholar 

  5. McGrath JA, Hoeger PH, Christiano AM, et al. Skin fragility and hypohidrotic ectodermal dysplasia resulting from ablation of plakophilin 1. Br J Dermatol. 1999;140:297–307.

    Article  CAS  PubMed  Google Scholar 

  6. Whittock NV, Haftek M, Angoulvant N, et al. Genomic amplification of the human plakophilin 1 gene and detection of a new mutation in ectodermal dysplasia/skin fragility syndrome. J Invest Dermatol. 2000;15:368–74.

    Article  Google Scholar 

  7. Hamada T, South AP, Mitsuhashi Y, et al. Genotype-phenotype correlation in skin fragility-ectodermal dysplasia syndrome resulting from mutations in plakophilin 1. Exp Dermatol. 2002;11:107–14.

    Article  CAS  PubMed  Google Scholar 

  8. Sprecher E, Molho-Pessach V, Ingber A, Sagi E, Indelman M, Bergman R. Homozygous splice site mutations in PKP1 result in loss of epidermal plakophilin 1 expression and underlie ectodermal dysplasia/skin fragility syndrome in two consanguineous families. J Invest Dermatol. 2004;122:647–51.

    Article  CAS  PubMed  Google Scholar 

  9. Steijlen PM, van Steensel MA, Jansen BJ, et al. Cryptic splicing at a non-consensus splice-donor in a patient with a novel mutation in the plakophilin 1 gene. J Invest Dermatol. 2004;122:1321–4.

    Article  PubMed  Google Scholar 

  10. Zheng R, Bu DF, Zhu XJ. Compound heterozygosity for new splice site mutations in the plakophilin 1 gene (PKP1) in a Chinese case of ectodermal dysplasia-skin fragility syndrome. Acta Derm Venereol. 2005;85:394–9.

    Article  CAS  PubMed  Google Scholar 

  11. Ersoy-Evans S, Erkin G, Fassihi H, et al. Ectodermal dysplasia-skin fragility syndrome resulting from a new homozygous mutation, 888delC, in the desmosomal protein plakophilin 1. J Am Acad Dermatol. 2006;55:157–61.

    Article  PubMed  Google Scholar 

  12. Tanaka A, Lai-Cheong JE, Café ME, et al. Novel truncating mutations in PKP1 and DSP cause similar skin phenotypes in two Brazilian families. Br J Dermatol. 2009;160:692–7.

    Article  CAS  PubMed  Google Scholar 

  13. Adhe VS, Dongre AM, Khopkar US. Ectodermal dysplasia-skin fragility syndrome. Indian J Dermatol Venereol Leprology. 2011;77:503–6.

    Article  Google Scholar 

  14. Boyce AE, McGrath JA, Techanukul T, et al. Ectodermal dysplasia-skin fragility syndrome due to a new homozygous internal deletion mutation in the PKP1 gene. Australas J Dermatol. 2012;53:61–5.

    Article  PubMed  Google Scholar 

  15. Hernandez-Martin A, Torrelo A, Ciria S et al. Ectodermal dysplasia-skin fragility syndrome: a novel mutation in the PKP1 gene. Clin Exp Dermatol 2013;38:787–90.

    Google Scholar 

  16. Fine JD, Eady RA, Bauer EA, Bauer JW, 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;58:931–50.

    Article  PubMed  Google Scholar 

  17. Olivry T, Linder KE, Wang P, et al. Deficient plakophilin-1 expression due to a mutation in PKP1 causes ectodermal dysplasia-skin fragility syndrome in Chesapeake Bay retriever dogs. PLoS One. 2012;7:e32072.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  18. McMillan JR, Haftek M, Akiyama M, et al. Alterations in desmosome size and number coincide with the loss of keratinocyte cohesion in skin with homozygous and heterozygous defects in the desmosomal protein plakophilin 1. J Invest Dermatol. 2003;121:96–103.

    Article  CAS  PubMed  Google Scholar 

  19. Hatzfeld M. Plakophilins: multifunctional proteins or just regulators of desmosomal adhesion? Biochim Biophys Acta. 2007;1773:69–77.

    Article  CAS  PubMed  Google Scholar 

  20. Hatzfeld M, Haffner C, Schulze K, Vinzens U. The function of plakophilin-1 in desmosome assembly and actin filament organization. J Cell Biol. 2000;149:209–22.

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  21. Kowalczyk AP, Hatzfeld M, Bornslaeger EA, et al. The head domain of plakophilin-1 binds to desmoplakin and enhances its recruitment to desmosomes. Implications for cutaneous disease. J Biol Chem. 1999;274:18145–8.

    Article  CAS  PubMed  Google Scholar 

  22. Schmidt A, Langbein L, Rode M, Prätzel S, Zimbelmann R, Franke WW. Plakophilins 1a and 1b: widespread nuclear proteins recruited in specific epithelial cells as desmosomal plaque components. Cell Tissue Res. 1997;290:481–99.

    Article  CAS  PubMed  Google Scholar 

  23. Sobolik-Delmaire T, Reddy R, Pashaj A, Roberts BJ, Wahl 3rd JK. Plakophilin-1 localizes to the nucleus and interacts with single-stranded DNA. J Invest Dermatol. 2010;130:2638–46.

    Article  CAS  PubMed  Google Scholar 

  24. Sobolik-Delmaire T, Katafiasz D, Wahl 3rd JK. Carboxyl terminus of plakophilin 1 recruits to its plasma membrane, whereas amino terminus recruits desmoplakin and promotes desmosome assembly. J Biol Chem. 2006;281:16962–70.

    Article  CAS  PubMed  Google Scholar 

  25. Wolf A, Hatzfeld M. A role of plakophilins in the regulation of translation. Cell Cycle. 2010;9:2973–8.

    CAS  PubMed  Google Scholar 

  26. Kaz AM, Luo Y, Dzieciatkowski S, et al. Aberrantly methylated PKP1 in the progression of Barrett’s esophagus to esophageal adenocarcinoma. Gene Chromosome Cancer. 2012;51:384–93.

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Genetic Skin Disease Group, St John’s Institute of Dermatology, King’s College London, Guy’s Hospital, London, UK

    John A. McGrath MB, BS, MD, FRCP, FMedSci

Authors
  1. John A. McGrath MB, BS, MD, FRCP, FMedSci
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Correspondence to John A. McGrath MB, BS, MD, FRCP, FMedSci .

Editor information

Editors and Affiliations

  1. Department of Dermatology, St George Hospital, University of New South Wales, Sydney, New South Wales, Australia

    Dédée F. Murrell

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McGrath, J.A. (2015). Ectodermal Dysplasia Skin Fragility Syndrome. In: Murrell, D. (eds) Blistering Diseases. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-662-45698-9_27

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  • DOI: https://doi.org/10.1007/978-3-662-45698-9_27

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  • Publisher Name: Springer, Berlin, Heidelberg

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  • Online ISBN: 978-3-662-45698-9

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