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Previous Volume 340:692-702 March 4, 1999 Number 9 Next

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ABSTRACT

Background The hyper-IgE syndrome with recurrent infections is a rare immunodeficiency characterized by recurrent skin and pulmonary abscesses and extremely elevated levels of IgE in serum. Associated facial and skeletal features 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 dental examinations, took anthropometric measurements, and conducted laboratory studies.

Results Nonimmunologic features of the hyper-IgE syndrome were present in all patients older than eight years. Seventy-two percent had the previously unrecognized feature of failure or delay of shedding of the primary teeth owing to lack of root resorption. Common findings among patients were recurrent fractures (in 57 percent of patients), hyperextensible joints (in 68 percent), and scoliosis (in 76 percent of patients 16 years of age or older). The classic triad of abscesses, pneumonia, and an elevated IgE level was identified in 77 percent of all patients and in 85 percent of those older than 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 transmission 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 immunologic, dental, and skeletal features of the hyper-IgE syndrome.

Conclusions The hyper-IgE syndrome is a multisystem disorder that affects the dentition, the skeleton, connective tissue, and the immune system. It is inherited as a single-locus autosomal dominant trait with variable expressivity.

Source Information

From the Genetics and Molecular Biology Branch (B.G., J.M.P.) and the Genetic Disease Branch (F.G.), National Human Genome Research Institute; the Laboratory of Host Defenses, National Institute of Allergy and Infectious Diseases (S.M.H., J.I.G., H.L.M., J.A.M.); the Department of Radiology, Warren Grant Magnuson Clinical Center (S.C.H.); and the Clinical Research Core, National Institute of Dental and Craniofacial Research (A.C.O.) — all at the National Institutes of Health, Bethesda, Md.

Address reprint requests to Dr. Puck at the Immunologic Genetics Section, GMBB/NHGRI, Bldg. 49, Rm. 3A14, 40 Convent Dr., Bethesda, MD 20892-4442, or at jpuck{at}nhgri.nih.gov.

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Hyper-IgE Syndrome
Presotto F., Trentin L., Agostini C., Feingold M., Grimbacher B., Holland S. M., Puck J. M.
Extract | Full Text  
N Engl J Med 1999; 341:375-377, Jul 29, 1999. Correspondence

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