WHIM syndrome is a dominantly inherited primary immunodeficiency disorder 
representing the first identified example of human disease caused by mutations 
in the gene encoding for the chemokine receptor CXCR4. Pathogenesis is mediated 
by CXCR4 hyperfunction, leading to increased responsiveness to its unique ligand 
CXCL12 (also known as SDF-1). The altered CXCR4/CXCL12 interaction likely 
impairs cellular homeostasis and trafficking, resulting in immunological 
dysfunctions. The acronym WHIM resumes the main features of the syndrome: Warts, 
Hypogammaglobulinemia, Infections and Myelokathexis, which is abnormal retention 
of mature neutrophils in the bone marrow. WHIM patients suffer from recurrent 
bacterial infections since childhood and manifest a specific susceptibility to 
HPV infections. Hematological findings include neutropenia, lymphopenia and 
hypogammaglobulinemia. Because of the rarity of the disease and the 
heterogeneity in clinical presentation, diagnosis is often delayed. In the 
majority of patients, the phenotype is incomplete at the onset and WHIM syndrome 
is not suspected. Early identification may improve clinical and therapeutic 
management. Symptomatic treatments include G-CSF, substitutive immunoglobulins 
and antibiotic prophylaxis. A new therapeutic strategy might include the potent 
inhibitor of CXCR4 function plerixafor (Mozobil), as an agent specifically 
targeting the molecular defect in order to attenuate the phenotypic 
manifestations of the syndrome.