Abstract
Ectodermal dysplasias (ED) are uncommon genetic disorders resulting in abnormalities in ectodermally derived structures. Many ED-associated genes have been described, of which ectodysplasin-A (EDA) is one of the more common. The NF-κB essential modulator (NEMO encoded by the IKBKG gene) is unique in that mutations result in severe humoral and cellular immunologic defects in addition to ED. We describe three unrelated kindreds with defects in both EDA and IKBKG resulting from X-chromosome crossover. This demonstrates the importance of thorough immunologic consideration of patients with ED even when an EDA etiology is confirmed, and raises the possibility of a specific phenotype arising from coincident mutations in EDA and IKBKG.
Highlights
Ectodermal dysplasias (ED) comprise over 150 heterogeneous phenotypes in which the formation of structures arising from the ectodermal cell layer is impaired to some degree
80% of cases of hypohidrotic ectodermal dysplasia (HED) are caused by mutations in the gene EDA (OMIM 305100, XLHED, ectodermal dysplasia, type 1; ED1) on the X-chromosome, while a smaller subset of cases is caused by mutations in the EDAR, the adapter protein EDARADD, or WNT10A (Chassaing et al, 2010; Cluzeau et al, 2011)
Diarrhea, and failure to thrive in the first months of life, which was considered to be a result of food allergy
Summary
Ectodermal dysplasias (ED) comprise over 150 heterogeneous phenotypes in which the formation of structures arising from the ectodermal cell layer is impaired to some degree. EDA is a membrane-bound signaling molecule of the TNF superfamily and via interaction with its EDA-receptor (EDAR, a TNF superfamily receptor) plays a role in signaling between ectodermal and mesodermal cell layers during embryogenesis (Mikkola and Thesleff, 2003) Defects in this pathway result in hypohidrotic ectodermal dysplasia (HED), characterized by absent sweat glands, hypodontia/oligodontia, hypotrichosis, eczema, and distinctive facial features including frontal bossing and a depressed nasal bridge. 80% of cases of HED are caused by mutations in the gene EDA (OMIM 305100, XLHED, ectodermal dysplasia, type 1; ED1) on the X-chromosome, while a smaller subset of cases is caused by mutations in the EDAR, the adapter protein EDARADD, or WNT10A (Chassaing et al, 2010; Cluzeau et al, 2011). Defects in these latter genes can manifest with autosomal recessive (ectodermal dysplasia anhidrotic; EDA; OMIM 224900) and autosomal dominant forms (ectodermal dysplasia type 3; ED3; OMIM 129490)
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