Skin and Mucosal Manifestations in NEMO Syndrome: A Case Series and Literature Review

Objectives: To characterize the skin and mucosal findings of NEMO syndrome.

Methods: Retrospective review of clinical characteristics from a cohort of two families with mutations in IKBKG (the NEMO-encoding gene). A literature review identified 86 studies describing 192 patients with IKBKG mutations whose data were also included.

Setting: Single center with literature review.

Participants: Patients with mutations in IKBKG from our center and reported in the literature.

Main outcomes and measures: Skin and mucosal characteristics of patients with NEMO syndrome.

Results: In addition to ectodermal dysplasia and recurrent infections, male patients had findings of ichthyosis, palmoplantar keratoderma, and inflammatory skin diseases. Both male and female patients had mucocutaneous ulcers and slow-to-heal chronic wounds. In combination with patients from the literature, 59% (85/144) of males had ectodermal dysplasia with anhidrosis (EDA) features, and 8% and 10% (12/144; 6/63) of males and females had dental findings, respectively. 4% (6/144) of males and 32% (20/63) of females had mucocutaneous ulcers. Ichthyosis/xerosis was present in 15% of males (21/144) but only 2% (1/63) females. Similarly, 13% (18/144) of male patients presented with dermatitis while this was reported in only 2% (1/63) of females.

Conclusions: Our results both confirm and expand upon the known spectrum of mucocutaneous findings in NEMO syndrome. Further genetic studies are needed to correlate specific mutations to clinical and morphologic subtypes.