A novel form of Non-X-linked HyperIgM (NXHIGM) syndrome associated with growth and pubertal disturbances and with lymphoma development

HyperIgM syndrome (HIGM) includes a heterogenous group of inherited disorders characterized by increased susceptibility to recurrent bacterial infections, normal or elevated serum IgM levels, and reduced or absent IgG, IgA, and IgE levels. Different molecular defects have been identified as being responsible for HIGM: the X-linked CD40-L1 and the autosomal recessive (AR) CD402 deficiencies associate a T- and B-cell defect, although the AR activation-induced cytidine deaminase3 (AID) and uracil-N glycosylase4 (UNG) deficiencies result in a pure B-cell defect. Most HIGM, however, remain molecularly undefined.5 In this paper, we report on an HIGM associated with growth retardation and pubertal retardation in two unrelated female patients. Severe lymphoid hyperplasia evolved during the clinical course of this disease, with eventual development of B cell lymphoma. Bone defects and Arnold-Chiari syndrome were also present in one patient. Although the molecular defect underlying this syndrome remains undefined, clinical, immunologic, and histologic data clearly differentiate this form of HIGM from previously reported HIGM syndromes.