WHIM Syndrome

Diseases of the Immune System Primary Immunodeficiencies

WHIM Syndrome


The information on the Rare Awareness Rare Education (RARE) Portal is intended for educational purposes only and does not replace professional advice.

Rare diseases typically display a high level of symptom complexity and variability. Individuals diagnosed with the same rare disease may be impacted differently and each person’s experience is unique. Please seek support from qualified healthcare professionals to learn more about the most suitable care and support options for you.

For more information on this disease, please refer to Genetic and Rare Diseases (GARD) Information Center – WHIM Syndrome.1

If you are aware of any additional information that may benefit stakeholders with an interest in this page, or if you notice any broken links or inaccurate information, please let us know via the Contribute page.

Emergency Management

There may be special considerations for the emergency management of individuals living with WHIM Syndrome presenting to emergency departments.

WHIM Syndrome is a primary immunodeficiency disorder.2 Individuals with WHIM Syndrome often have low levels of antibodies (immunoglobulins) and blood neutrophils (neutropenia; caused by myelokathexis). They are prone to getting infections, particularly bacterial infections.2,3

Clinical Care Guidelines

If you know of any clinical care guidelines for WHIM Syndrome in Australia or internationally, please let us know via the Contribute page.


WILM; Warts-hypogammaglobulinemia-infections-myelokathexis syndrome; Warts-infections-leukopenia-myelokatexis syndrome


ICD-11: 4A00.Y Other specified primary immunodeficiencies due to disorders of innate immunity


WHIM Syndrome is a primary immunodeficiency disorder2, in which the immune system is not able to work properly due to a genetic cause. WHIM Syndrome is caused by gain-of-function mutations in the CXCR4 gene.3,4 These gain-of-function mutations cause the CXCR4 chemokine receptor, which is involved in many biological processes including immunity, to behave abnormally.4

WHIM stands for four of the main features of the condition – warts (W), hypogammaglobulinemia (H), infections (I), and myelokathexis (M).1-3,5 Hypogammaglobulinemia is when there are low levels of antibodies (immunoglobulins) in the immune system.6 Myelokathexis is a condition where neutrophils (a type of white blood cell of the immune system) stays in the bone marrow instead of being released into the bloodstream – this results in low number of neutrophils in the blood (neutropenia).4

Individuals with WHIM Syndrome often have repeated (recurrent) infections, particularly bacterial infections.2,3 This can lead to further complications, such as hearing loss.2,4,5 They also often develop warts due to human papillomavirus (HPV) infection and may be at higher risk of certain types of cancers.2-5


Symptoms usually appear during early childhood, starting with recurrent bacterial infections.2,3 Individuals with WHIM Syndrome are also at risk of viral and fungal infections.2 They may develop warts due to human papillomavirus (HPV) infection – the warts may be widespread and difficult to treat.2,3

Individuals with WHIM may develop further complications/are more at risk of complications, such as bronchiectasis and hearing loss, and are at higher risk of certain forms of cancer.2,5 They may also have poor response to vaccinations, in that there are low or no detection of the expected antibodies and immune response to the vaccine.3,4

Some individuals may not experience all the characteristic symptoms (incomplete penetrance). The severity of symptoms may also vary between individuals.5

Please speak to your medical team to learn more about the symptoms and complications of Whim Syndrome.


WHIM Syndrome is usually caused by gain-of-function mutations in the CXCR4 gene (which codes for chemokine receptor CXCR4).3,4 These gain-of-function mutations cause the CXCR4 protein to behave abnormally. The mutations are inherited in an autosomal dominant manner3,4, with one copy of the mutation sufficient to cause WHIM Syndrome.

Information about autosomal dominant inheritance can be found at: Factsheet: Autosomal dominant inheritance (NSW Government Health: Centre for Genetics Education).

If you would like to learn more about the inheritance and impact of this condition, please ask your doctor for a referral to a genetic counsellor. Genetic counsellors are qualified allied health professionals who can provide information and support regarding genetic conditions and testing. More information on genetic counselling can be found on the National Services page and specific State and Territory Services pages on the RARE Portal.


Diagnosis of WHIM Syndrome may be based on detailed patient history, clinical examination, blood tests to look at cell blood counts and genetic testing for mutations in the CXCR4 gene.3,5 A bone marrow biopsy may be used to detect for levels of blood cells in the bone marrow, with high levels indicative of myelokathexis.

It is recommended that a diagnosis of WHIM Syndrome should be considered in cases where there are frequent bacterial infections early on in life, even if no warts have been observed.5


There is no standardised consensus treatment for WHIM Syndrome.4 Current practices are targeted at symptoms, such as treating infections and warts, use of granulocyte-colony stimulating factor (GCSF) to improve the neutropenia, and immunoglobulin replacement therapy for the hypogammaglobulinemia.3,4 Individuals with frequent infections may also be given prophylactic antibiotics to prevent further infections. 3,4

Individuals with WHIM Syndrome should be monitored for complications, such as bronchiectasis, hearing loss and certain types of cancer, to enable timely interventions.7

It is best to speak with your medical team to learn more about possible treatments and management strategies for WHIM Syndrome and its associated complications.

Clinical Care

Healthcare professionals involved in the treatment of WHIM Syndrome may include general practitioners (GP), geneticists, and allergists/immunologists.1 The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.


Please visit Australian Clinical Trials to learn about clinical trials for WHIM Syndrome in Australia; there may not be any clinical trials currently available.

Information regarding clinical trials for WHIM Syndrome in other countries can be found at ClinicalTrials.gov; there may not be any clinical trials currently available.

It is best to discuss your interest in any clinical trials with your medical team to determine suitability and eligibility.

Rare Disease Organisation(s)

Immune Deficiencies Foundation Australia (IDFA)
Website: https://www.idfa.org.au/
Phone: 1800 100 198
Email: [email protected]

IDFA is a national not-for-profit and leading peak body offering education, advocacy and awareness for Australians living with primary or secondary immunodeficiencies.

If you are aware of any organisations specifically for WHIM Syndrome in Australia, please let us know via the Contribute page.

Please note that RVA does not necessarily monitor or endorse each group/organisation’s operational governance.

Social Services

For information on available government and social services that provide support for individuals with a rare disease, please visit the National and State Services pages.

Mental Health

Please visit the ‘Mental Health’ sections listed on the National and State Services pages.


Further information on WHIM Syndrome can be found at:

  1. Genetic and Rare Diseases (GARD) Information Center. WHIM Syndrome. Accessed 24 October 2023. https://rarediseases.info.nih.gov/diseases/9297/whim-syndrome
  2. Orphanet. WHIM Syndrome. Accessed 24 October 2023. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=51636
  3. National Organization for Rare Disorders (NORD). WHIM Syndrome. Accessed 24 October 2023. https://rarediseases.org/rare-diseases/whim-syndrome/
  4. Heusinkveld LE, Majumdar S, Gao J, et al. WHIM Syndrome: from Pathogenesis towards Personalized Medicine and Cure. J. Clin. Immunol. 2019; 39(6):532-556. Available from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6698215/
  5. 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;42:1748 1765. https://doi.org/10.1007/s10875-022-01312-7
  6. Cleveland Clinic. Hypogammaglobulinemia. Accessed 14 November 2023. https://my.clevelandclinic.org/health/diseases/25195-hypogammaglobulinemia
  7. Dotta L, Notarangelo LD, Moratto D, et al. Long term outcome of WHIM syndrome in 18 patients: high risk of lung disease and HPV-related malignancies. J. Allergy Clin. Immunol. Pract. 2019;7(5):1568-1577. https://doi.org/10.1016/j.jaip.2019.01.045
Page Last Updated

07/03/2024 09:19