Hyper-IgE syndrome with recurrent infections - An autosomal dominant multisystem disorder

Background The hyper-IgE syndrome with recurrent infections is a rare immun odeficiency characterized by recurrent skin and pulmonary abscesses and ext remely elevated levels of IgE in serum. Associated facial and skeletal feat ures have been recognized, but their frequency is unknown, and the genetic basis of the hyper-IgE syndrome is poorly understood. Methods We studied 30 patients with the hyper-IgE syndrome and 70 of their relatives. We took histories, reviewed records, performed physical and dent al examinations, took anthropometric measurements, and conducted laboratory studies. Results Nonimmunologic features of the hyper-IgE syndrome were present in a ll patients older than eight years. Seventy-two percent had the previously unrecognized feature of failure or delay of shedding of the primary teeth o wing to lack of root resorption. Common findings among patients were recurr ent fractures (in 57 percent of patients), hyperextensible joints (in 68 pe rcent), and scoliosis tin 76 percent of patients 16 years of age or older). The classic triad of abscesses, pneumonia, and an elevated IgE level was i dentified in 77 percent of all patients and in 85 percent of those older th an eight. In 6 of 23 adults (26 percent), IgE levels declined over time and came closer to or fell within the normal range. Autosomal dominant transmi ssion of the hyper-IgE syndrome was found, but with variable expressivity. Of the 27 relatives at risk for inheriting the hyper-IgE syndrome, 10 were fully affected, 11 were unaffected, and 6 had combinations of mild immunolo gic, dental, and skeletal features of the hyper-IgE syndrome. Conclusions The hyper-IgE syndrome is a multisystem disorder that affects t he dentition, the skeleton, connective tissue, and the immune system. It is inherited as a single-locus autosomal dominant trait with variable express ivity. (N Engl J Med 1999;340:692-702.) (C) 1999, Massachusetts Medical Soc iety.