Ectodermal Dysplasia, Anhidrotic, with Immunodeficiency 2 D84.9

Ectodermal dysplasia with immunodeficiency 2 (EDAID2) is characterized by variable features of ectodermal dysplasia (e.g., hypo-/anhidrosis, sparse hairiness, dental abnormalities) and various immunological and infectious phenotypes of varying severity (see Boisson et al. 2017). This phenotype of ectodermal dysplasia is associated with mutations in the NFKBIA gene.

Mutations in the NFKBIA gene result in functional impairment of NFKB, a master transcription factor required for normal activation of immune responses. Disruption of NFKB signaling leads to decreased production of proinflammatory cytokines and certain interferons, making patients susceptible to infection (McDonald et al. 2007).

1. Boisson B et al. (2017) Human I-kappa-B-alpha gain of function: a severe and syndromic immunodeficiency. J Clin Immun 37: 397-412.
2. Courtois G et al (2003) A hypermorphic I-kappa-B-alpha mutation is associated with autosomal dominant anhidrotic ectodermal dysplasia and T cell immunodeficiency. J Clin Invest 112: 1108-1115.
3. McDonald DR et al (2007) Heterozygous N-terminal deletion of I-kappa-B-alpha results in functional nuclear factor kappa-B haploinsufficiency, ectodermal dysplasia, and immune deficiency. J Allergy Clin Immun 120: 900-907.