Hyper-IgE syndrome (HIES, Job syndrome) is characterized by a triad of elevated IgE, skin abscesses and cyst-forming pneumonia. Non-immunological characteristics of this syndrome (skeletal anomalies, scoliosis, retention of primary teeth, osteoporosis, pathologic fractures, characteristic facies and hyperextensibility) have been described in detail only recently. Some of these characteristics as well as the severe infectious complications may not be apparent until late childhood or adolescence. Our objective was to study the association of HIES with skeletal anomalies that are detectable in the early years.

We reviewed our data from 159 subjects in 49 families evaluated for possible HIES at the National Institutes of Health. Congenital skeletal anomalies were detected by radiological assessment of the skull, spine and long bones.

HIES was diagnosed in 52 patients. Ten of these patients had not had either skin abscesses or a history of pneumonias by the time of diagnosis, but presented with the other components of this syndrome and/or a fully affected first degree relative. Seventeen of the 52 HIES patients (32%) had at least one congenital skeletal anomaly, in contrast to 5 of 107 (4.7%) subjects in whom HIES was not confirmed (p=0.002). Some of the observed skeletal anomalies were: craniosynostosis, hemivertebrae, short limbs, spina bifida, bifid rib and Blount's disease.

HIES patients have an increased incidence of congenital skeletal anomalies. Physicians should look for skeletal anomalies when considering HIES, especially in patients too young to have enough manifestations of HIES to make a definitive diagnosis.