WHIM syndrome is predominantly caused by an autosomal dominant pathogenic variant in the CXCR4 gene.1

Mechanism of Disease: CXCR4 Pathway Dysregulation Pathological Feature: Myelokathexis

Pathogenic variants of the CXCR4 gene can result in the retention of white blood cells in the bone marrow.1

WHIM MOA Graphic

Myelokathexis, the abnormal retention of neutrophils in the bone marrow, is a hallmark feature of WHIM syndrome, present in ~100% of cases. It is detected by bone marrow biopsy but can be challenging to identify and may be missed on initial biopsy evaluation.1,3-6

Bone Marrow Aspirates of WHIM Syndrome Patients Showing Key Pathological Features of Myelokathexis*,†,2,6

WHIM Myelokathexis Biopsy Image

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No-cost genetic testing is available for qualified U.S. patients who may have a congenital neutropenic disorder or a primary immunodeficiency, including WHIM syndrome.

Next Section: Diagnosis & Management

  1. Geier CB, Ellison M, Cruz R, et al. Disease progression of WHIM syndrome in an international cohort of 66 pediatric and adult patients. J Clin Immunol. 2022;42(8):1748-1765. doi:10.1007/s10875-022-01312-7
  2. Beaussant Cohen S, Fenneteau O, Plouvier E, et al. Description and outcome of a cohort of 8 patients with WHIM syndrome from the French Severe Chronic Neutropenia Registry. Orphanet J Rare Dis. 2012;7:71. doi:10.1186/1750-1172-7-71
  3. Heusinkveld LE, Majumdar S, Gao JL, McDermott DH, Murphy PM. WHIM syndrome: from pathogenesis towards personalized medicine and cure. J Clin Immunol. 2019;39(6):532-556. doi:10.1007/s10875-019-00665-w
  4. Badolato R, Donadieu J; WHIM Research Group. How I treat warts, hypogammaglobulinemia, infections, and myelokathexis syndrome. Blood. 2017;130(23):2491-2498. doi:10.1182/blood-2017-02-708552
  5. McDermott DH, Murphy PM. WHIM syndrome: Immunopathogenesis, treatment and cure strategies. Immunol Rev. 2019;287(1):91-102. doi:10.1111/imr.12719
  6. Al Ustwani O, Kurzrock R, Wetzler M. Genetics on a WHIM. Br J Haematol. 2014;164(1):15-23. doi:10.1111/bjh.12574