Hypohidrotic ectodermal dysplasia and immunodeficiency with coincident NEMO and EDA mutations

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 demon- strates 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. © 2011 Keller, Petersen, Ong, Church, Risma, Burham, Jain, Stiehm, Hanson, Uzel, Deardorff and Orange.