WHIM syndrome is a primary immunodeficiency disorder,¹ in which the immune system is not able to work properly due to a genetic cause. WHIM syndrome is caused by gain-of-function genetic changes (variants) in the CXCR4 gene.^2,3 These genetic variants cause the CXCR4 chemokine receptor, which is involved in many biological processes including immunity, to behave abnormally.³

WHIM stands for four of the main features of the condition:^1,2,4,5

• Warts
• Hypogammaglobulinemia – when there are low levels of antibodies (immunoglobulins) in the immune system.⁶
• Infections
• Myelokathexis – 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.^1,2 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.^{1-3, 5} 

Synonyms: WILM; Warts-hypogammaglobulinemia-infections-myelokathexis syndrome; Warts-infections-leukopenia-myelokatexis syndrome.¹

Universal rare disease classifications provide a common language for recording, reporting and monitoring diseases. Please visit the Rare Disease Classifications page for more information about these internationally recognised classifications.

ORPHA:51636 WHIM syndrome

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

Symptoms usually appear during early childhood, starting with recurrent bacterial infections.^1,2 Individuals with WHIM syndrome are also at risk of viral and fungal infections.¹ They may develop warts due to human papillomavirus (HPV) infection – the warts may be widespread and difficult to treat.^1,2

Individuals with WHIM syndrome 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.^1,5 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.^2,3

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.

Rare diseases are often serious and progressive, exhibiting a high degree of symptom complexity, leading to significant disability. Majority of the estimated two million Australians living with a rare disease meet the Australian Government’s definition for disability (in accordance to the Australian Public Service Commission and Australian Bureau of Statistics), and many experience severe and permanent disability impacts. If you or someone you care for is experiencing disability-related impacts from a rare condition, please speak with a health or disability professional for advice. Information about relevant disability support can be found at the RARE Portal’s Disability Support Information page.

In most cases reported, WHIM syndrome is caused by disease-causing genetic changes (variants)  in the CXCR4 gene (which codes for chemokine receptor CXCR4).^2,3 For more information on different types of genetic variants, please refer to Centre for Genetics Education: Types of genetic variation.

WHIM syndrome can be passed down (inherited) from their parents or occurs randomly (de novo) prior to birth.²

For most individuals with WHIM syndrome, the genetic variants are inherited in an autosomal dominant pattern – a genetic variant in just one of the CXCR4 gene copies can result in WHIM syndrome.^1,2 In some cases, WHIM syndrome is inherited in an autosomal recessive pattern – genetic variants in both CXCR4 gene copies are needed to result in WHIM syndrome.

More information about inheritance patterns can be found at:

• Centre for Genetics Education: Autosomal dominant inheritance
• Centre for Genetics Education: Autosomal recessive inheritance

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 about genetic counselling can be found at:

• Information on Genetic Services
• The National and State Services pages underneath the ‘Genetic Counselling’ sections listed

Diagnosis of WHIM syndrome may be based on medical history, clinical examination, blood tests to look at cell blood counts and confirmed with genetic testing for CXCR4 gene.^2,5 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 be considered in cases where there are frequent bacterial infections early on in life, even if no warts have been observed.⁵

A differential diagnosis can rule out other conditions that have similar symptoms, such as autosomal dominant severe congenital neutropenia, autosomal recessive severe congenital neutropenia due to G6PC3 deficiency, epidermodysplasia verruciformis, and monocytopenia with susceptibility to infections.¹

Please speak to your medical team to learn more about the available diagnostic pathways for WHIM syndrome.

There is currently no curative or standardised consensus treatment for WHIM syndrome.³ Treatment is targeted at managing symptoms (symptomatic management), such as treating infections and warts, use of granulocyte-colony stimulating factor (GCSF) to improve the neutropenia, and immunoglobulin replacement therapy for the hypogammaglobulinemia.^2,3 Individuals with frequent infections may also be given prophylactic antibiotics to prevent further infections.^2,3

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

Please speak to your medical team to learn more about the possible treatment or management options for your condition. Treatment will depend on an individual’s specific condition and symptoms. It is also important to stay connected to your medical team so that you can be made aware of any upcoming clinical trial opportunities.

Clinical care for rare diseases often involves a multidisciplinary team of medical, care and support professionals. Please note that the information provided here is as a guide and that RVA does not necessarily monitor or endorse specific clinics or health experts.

Healthcare professionals involved in the treatment of WHIM syndrome may include general practitioners (GP), geneticists, and allergists/immunologists.⁴ The need for different healthcare professionals may change over a person’s lifetime and extend beyond those listed here.

We are not aware of any clinical care guidelines for WHIM syndrome in Australia. If you know of any relevant care guidelines, please let us know via the Contribute page.

Individuals living with rare diseases may have complex medical issues and disabilities, which are not always visible. It is often useful to refer to their medical history as well as personal information such as a medical card, doctor’s letter, or if available, a rare disease passport, for relevant information.

It may be important to consider the following when managing individuals living with WHIM syndrome at emergency departments/services:

• WHIM syndrome is a primary immunodeficiency disorder.¹ 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.^1,2

There are specific considerations around participating in rare disease research, including clinical trials. It is important to be mindful of issues such as data privacy, research ethics, consent and differences in research regulations between Australia and other countries.

If you are interested in finding clinical trials for your condition, please visit the following websites; however, there may not be any clinical trials available:

• Australian Clinical Trials
• ClinicalTrials.gov

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

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

Australian Organisation:

Immune Deficiencies Foundation Australia (IDFA)
Website: https://www.idfa.org.au/

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

Please note that RVA does not monitor or endorse each group/organisation’s operational governance and activities. When engaging with a group, please consider the information on the RARE Portal’s Finding Helpful Peer and Community Supports page.

WHIM syndrome vary between individuals, and each person’s experience is unique.

If you would like to share your personal story with RVA, please visit the Rare Voices Australia: Share Your Story page. RVA will consider your story for publishing on our website and inclusion on the RARE Portal.

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.

People living with a rare disease, including families and carers, often face unique challenges such as diagnostic delays, misdiagnoses, limited treatment options, and limited access to rare disease specialists and support. These challenges may impact people’s emotional wellbeing and quality of life. Many people find it helpful to seek mental health and wellbeing support to cope with ongoing stress and uncertainty. Connecting with people who have shared experiences through a support group may also be helpful. Information about relevant mental health and wellbeing support can be found at:

• Mental Health and Wellbeing Support for Australians Living with a Rare Disease
• The National and State Services pages underneath the ‘Mental Health’ sections listed

Further information on WHIM syndrome can be found at:

• National Organization for Rare Disorders (NORD): WHIM Syndrome

• Online Mendelian Inheritance in Man, OMIM^®: #193670 – Whim Syndrome 1; WHIMS1
• Orphanet: WHIM syndrome

This page has been developed by Rare Voices Australia (RVA)’s RARE Portal team.

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.