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March 1, 2008

X-Linked Ectodermal Dysplasia With Immunodeficiency Caused by NEMO Mutation: Early Recognition and Diagnosis

Author Affiliations

Author Affiliations: Division of Dermatology, Children's Memorial Hospital and Departments of Pediatrics and Dermatology, Northwestern University Feinberg School of Medicine, Chicago, Illinois (Drs Mancini and Lawley); and Laboratory of Clinical Infectious Diseases, National Institutes of Health, National Institute of Allergy and Infectious Diseases, Bethesda, Maryland (Dr Uzel).

Arch Dermatol. 2008;144(3):342-346. doi:10.1001/archderm.144.3.342

Background  X-linked ectodermal dysplasia with immunodeficiency (XL-EDA-ID) is described in patients with hypomorphic mutations in IKBKG (the inhibitory κB kinase γ gene), which encodes nuclear factor κB essential modulator (NEMO). Features include hypohidrosis, dental anomalies, alopecia, and immunodeficiency. Boys with NEMO mutations often present with serious infections, but the NEMO mutations are rarely diagnosed early in infancy. Cutaneous features in these patients are poorly elucidated.

Observations  A 12-week-old male infant presented with a recalcitrant skin eruption, intertrigo, atopiclike dermatitis, and erythroderma. Alopecia, frontal bossing, and periorbital wrinkling were present, and family history revealed incontinentia pigmenti in his mother. Laboratory evaluation revealed leukocytosis with eosinophilia, low IgG and IgM levels, and absent IgA. Flow cytometry revealed lymphocytosis with elevated CD3+ and CD4+ counts and low levels of natural killer cells. Amplification and sequencing of IKBKG revealed insertion of cytosine at nucleotide 1167 (1167-1168insC) in exon 10, with frameshift mutation in the zinc-finger domain. Peripheral blood stem cell transplantation led to initial engraftment and improvement in his skin findings, but his engrafted cell counts diminished, and a second stem cell transplantation was planned.

Conclusions  Mutations in NEMO should be considered in male infants with recalcitrant seborrheic or atopic dermatitislike eruptions and intertrigo, especially when features of ectodermal dysplasia are present. Early recognition and diagnosis are desirable, prior to the onset of manifestations of immunodeficiency.