Definitive

Male or female patient with chronic neutropenia (absolute neutrophil count of less than 500 /mL) and myelokathexis (retention of senescent neutrophils in bone marrow) and one of the following:
1. Mutation in the intracellular C-tail of CXCR4
2. Activating mutation of CXCR4

Probable

Male or female patient with chronic neutropenia (absolute neutrophil count of less than 500 /mL) and myelokathexis (retention of senescent neutrophils in bone marrow) and two of the following:

1. Chronic or recurrent warts
2. Chronic lymphopenia (absolute lymphocyte count of less tha 1500/mL)
3. Serum IgG at or bellow the normal range for age
4. A parent with neutropenia and warts

Possible

Male or female patient with chronic neutropenia (absolute neutrophil count of less than 500 /mL) and myelokathexis (retention of senescent neutrophils in bone marrow).

1. Ocular or facial telangiectasia
2. Serum IgA less than 2 SD below normal for age
3. Alpha fetoprotein more than 2 SD above normal for age
4. Increased chromosomal breakage after exposure to irradiation

Spectrum of disease

WHIM syndrome is an autosomal dominant disorder resulting in neutropenia with myelokathexis. Most patients present with recurrent infections at less than 3 years of age. Warts generally begin to appear after five years of age and some patients have hundreds of warts that can include plantar and genital warts. Increased susceptibility to infection from members of the herpes virus family can be seen. Lymphopenia is present in most patients and some patients have very low numbers of B cells. Hypogamaglobulinemia may be present, but the serum immunoglobulin concentrations do not correlate with the number of B cells. Most patients develop a normal neutrophil count during infection.

Source: ESID Newsletter 1/2006