Osteopetrosis, lymphedema, hypohidrotic ectodermal dysplasia, and 
immunodeficiency (OL-HED-ID) is a rare X-linked disorder with only three 
reported prior cases in the English-language literature. We describe a case of 
OL-HED-ID in a male infant who initially presented with congenital lymphedema, 
leukocytosis, and thrombocytopenia of unknown etiology at 7 days of age. He 
subsequently developed gram-negative sepsis and multiple opportunistic 
infections including high-level cytomegalovirus viremia and Pneumocystis 
jiroveci pneumonia. The infant was noted to have mildly xerotic skin, fine 
sparse hair, and periorbital wrinkling, all features suggestive of ectodermal 
dysplasia. Skeletal imaging showed findings consistent with osteopetrosis, and 
immunologic investigation revealed hypogammaglobulinemia and mixed T- and B-cell 
dysfunction. Genetic testing revealed a novel mutation in the nuclear factor 
kappa beta (NF-KB) essential modulator (NEMO) gene, confirming the diagnosis of 
OL-HED-ID. Mutations in the NEMO gene have been reported in association with 
hypohidrotic ectodermal dysplasia with immunodeficiency (HED-ID), OL-HED-ID, and 
incontinentia pigmenti. In this case, we report a novel mutation in the NEMO 
gene associated with OL-HED-ID. This article highlights the dermatologic 
manifestations of a rare disorder, OL-HED-ID, and underscores the importance of 
early recognition and prompt intervention to prevent life-threatening 
infections.