Patients exhibit increased susceptibility to bacterial and viral infections, especially from common serotype human papilloma virus, resulting in warts on the hands and feet starting in childhood. Myelokathexis refers to retention (kathexis) of neutrophils in the bone marrow (myelo). In addition, lymphocytes and IgG antibody levels (gammaglobulins) are often deficient.
WHIM syndrome has an autosomal dominant pattern of inheritance.
WHIM syndrome results from autosomal dominantmutations in the gene for the chemokine receptor, CXCR4, resulting in a carboxy-terminus truncation of the receptor of between ten and 19 residues. The gene mutant is located on 2q21. The truncation of the receptor protein results in the inability of downregulation after stimulation. Thus, the receptor remain in an activated state. WHIM syndrome is one of only a few diseases directly and primarily caused by an aberrant chemokine, making its molecular biology important in understanding the role of cell signaling and trafficking.
An association with GRK3 has also been observed.
Infusions of immune globulin can reduce the frequency of bacterial infections, and G-CSF or GM-CSF therapy improves blood neutrophil counts.
As WHIM syndrome is a molecular disease arising from gain-of-function mutations in CXCR4, preclinical studies identified plerixafor, a specific CXCR4 antagonist, as a potential mechanism-based therapeutic for the disease. Two subsequent clinical trials involving a handful of patients with WHIM syndrome demonstrated that plerixafor could increase white blood cell counts and continues to be a promising targeted therapy.
^Wetzler M, Talpaz M, Kleinerman ES, et al. (1990). "A new familial immunodeficiency disorder characterized by severe neutropenia, a defective marrow release mechanism, and hypogammaglobulinemia.". Am. J. Med.89 (5): 663. PMID2239986.