Encyclopedia of Medical Immunology

Living Edition
| Editors: Ian MacKay, Noel R. Rose

Anhidrotic Ectodermal Dysplasia with Immunodeficiency (EDA-ID), X-linked

  • Jacob RozmusEmail author
Living reference work entry
DOI: https://doi.org/10.1007/978-1-4614-9209-2_44-1



X-linked recessive EDA-ID (OMIM # 300291) is an immune deficiency with hypohidrotic ectodermal dysplasia caused by hypomorphic hemizygous mutations in IKBKG which encodes IKK-gamma/NF-kappa-B essential modulator (NEMO).


The NF-B signaling cascade is comprised of transcription factors that are normally sequestered in an inactive state in the cytoplasm. They are held in an inactive state through their interaction with IkB inhibitors. In response to a variety of immune and inflammatory stimuli, the IkB molecules become phosphorylated by an IkB kinase (IKK) core complex on two critical serine residues. This is a prerequisite to recognition by UBE2D3 leading to polyubiquitination and subsequent proteasomal degradation. This releases the NF-kB transcription factors and allows them to translocate into the nucleus where they initiate distinct profiles of gene expression depending on the cell...

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


  1. Carrol ED, Gennery AR, Flood TJ, et al. Anhidrotic ectodermal dysplasia and immunodeficiency: the role of NEMO. Arch Dis Child. 2003;88(4):340–1.CrossRefPubMedPubMedCentralGoogle Scholar
  2. Chandrakasan S, Marsh RA, Uzel G, et al. Outcome of patients with NEMO deficiency following allogeneic hematopoietic cell transplant. J Allergy Clin Immunol. 2017;139(3):1040–3.CrossRefPubMedGoogle Scholar
  3. Courtois G, Israël A. IKK regulation and human genetics. Curr Top Microbiol Immunol. 2011;349:73–95.PubMedGoogle Scholar
  4. Döffinger R, Smahi A, Bessia C, et al. X-linked anhidrotic ectodermal dysplasia with immunodeficiency is caused by impaired NF-kappaB signaling. Nat Genet. 2001;27(3):277–85.CrossRefPubMedGoogle Scholar
  5. Dupuis-Girod S, Corradini N, Hadj-Rabia S, et al. Osteopetrosis, lymphedema, anhidrotic ectodermal dysplasia, and immunodeficiency in a boy and incontinentia pigmenti in his mother. Pediatrics. 2002;109(6):e97.CrossRefPubMedGoogle Scholar
  6. Fusco F, Pescatore A, Conte MI, et al. EDA-ID and IP, two faces of the same coin: how the same IKBKG/NEMO mutation affecting the NF-kB pathway can cause immunodeficiency and/or inflammation. Int Rev Immunol. 2015;34(6):445–59.CrossRefPubMedGoogle Scholar
  7. Hubeau M, Ngadjeua F, Puel A, et al. New mechanism of X-linked anhidrotic ectodermal dysplasia with immunodeficiency: impairment of ubiquitin binding despite normal folding of NEMO protein. Blood. 2011;118(4):926–35.CrossRefPubMedPubMedCentralGoogle Scholar
  8. Israël A. The IKK complex, a central regulator of NF-kappaB activation. Cold Spring Harb Perspect Biol. 2010;2(3):a000158.CrossRefPubMedPubMedCentralGoogle Scholar
  9. Jain A, Ma CA, Lopez-Granados E, et al. Specific NEMO mutations impair CD40-mediated c-Rel activation and B cell terminal differentiation. J Clin Invest. 2004;114(11):1593–602.CrossRefPubMedPubMedCentralGoogle Scholar
  10. Karaca NE, Aksu G, Ulusoy E, et al. Disseminated BCG infectious disease and hyperferritinemia in a patient with a novel NEMO mutation. J Investig Allergol Clin Immunol. 2016;26(4):268–71.CrossRefGoogle Scholar
  11. Kawai T, Nishikomori R, Heike T. Diagnosis and treatment in anhidrotic ectodermal dysplasia with immunodeficiency. Allergol Int. 2012;61(2):207–17.CrossRefPubMedGoogle Scholar
  12. Ku CL, Yang K, Bustamante J, et al. Inherited disorders of human toll-like receptor signaling: immunological implications. Immunol Rev. 2005;203:10–20.CrossRefPubMedGoogle Scholar
  13. Maubach G, Naumann M. NEMO links nuclear factor-kB to human diseases. Trends Mol Med. 2017;23(12):1138–55.CrossRefPubMedGoogle Scholar
  14. Miot C, Imai K, Imai C, et al. Hematopoietic stem cell transplantation in 29 patients hemizygous for hypomorphic IKBKG/NEMO mutations. Blood. 2017;130(12):1456–67.CrossRefPubMedGoogle Scholar
  15. Mizukami T, Obara M, Nishikomori R, et al. Successful treatment with infliximab for inflammatory colitis in a patient with X-lined anhidrotic ectodermal dysplasia with immunodeficiency. J Clin Immunol. 2012;32(1):39–49.CrossRefPubMedGoogle Scholar
  16. Nishikomori R, Akutagawa H, Maruyama K, et al. X-linked ectodermal dysplasia and immunodeficiency caused by reversion mosaicism of NEMO reveals a critical role for NEMO in human T-cell development and/or survival. Blood. 2004;103(12):4565–72.CrossRefPubMedGoogle Scholar
  17. Orange JS, Brodeur SR, Jain A, et al. Deficient natural killer cell cytotoxicity in patients with IKK-gamma/NEMO mutations. J Clin Invest. 2002;109(11):1501–9.CrossRefPubMedPubMedCentralGoogle Scholar
  18. Perez EE, Orange JS, Bonilla F, et al. Update on the use of immunoglobulin in human disease: a review of evidence. J Allergy Clin Immunol. 2017;139(3S):S1–S46.CrossRefPubMedGoogle Scholar
  19. Picard C, Casanova JL, Puel A. Infectious diseases in patients with IRAK-4, MyD88, NEMO, or IkBalpa deficiency. Clin Microbiol Rev. 2011;24(3):490–7.CrossRefPubMedPubMedCentralGoogle Scholar
  20. Temmerman ST, Ma CA, Borges L, et al. Impaired dendritic-cell function in ectodermal dysplasia with immune deficiency is linked to defective NEMO ubiquitination. Blood. 2016;108(7):2324–31.CrossRefGoogle Scholar
  21. Vinolo E, Sebban H, Chaffotte A, et al. A point mutation in NEMO associated with anhidrotic ectodermal dysplasia with immunodeficiency pathology results in destabilization of the oligomer and reduces lipopolysaccharide and tumor necrosis factor-mediated NF-kappa B activation. J Biol Chem. 2006;281(10):6334–48.CrossRefPubMedGoogle Scholar
  22. Zonana J, Elder ME, Schneider LC, 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.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.BC Children’s Hospital, Department of PediatricsUniversity of British ColumbiaVancouverCanada

Section editors and affiliations

  • Stuart E. Turvey
    • 1
  1. 1.BC Children’s Hospital, Department of PediatricsUniversity of British ColumbiaVancouverCanada