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 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.

Keywords: EDA; NEMO; ectodermal dysplasia; immunodeficiency.

Figure 1

Family trees demonstrate the inheritance of EDA (red) and IKBKG (blue) mutations. (A) In the family of patient #1, a male maternal cousin of patient #1 (I7) had died with a diagnosis of granulomatous colitis. Multiple members also demonstrated dental abnormalities (D). (B) In the family of patient #2, the brother (I5) had features of ectodermal dysplasia (ED). No family history was available for family 3. (C) The respective positions of EDA and IKBKG on the long arm of the X-chromosome are depicted.

Figure 2

Lower extremity edema in patient #1.

Figure 3

Radiographs of patient #1 demonstrated osteopenia, multiple growth recovery lines, and diminished tubulation of long bones. DEXA showed lumbar spine L1–4 bone mineral density of 0.412 g/cm², Z-score = −1.0.