WHIM syndrome: warts, low antibodies, infections and myelokathexis explained

WHIM syndrome is a primary immunodeficiency, meaning a problem with the immune system that a person is born with. The name is an acronym for the four features that define it: warts, hypogammaglobulinaemia (low levels of antibodies), recurrent bacterial infections and myelokathexis. Myelokathexis refers to mature neutrophils, the white blood cells that fight bacteria, being retained in the bone marrow rather than released into the blood.

Not everyone with the condition has all four features. A 2025 study from the US National Institutes of Health describes it as an inborn error of immunity caused by pathogenic variants in the chemokine receptor CXCR4, and found that people with WHIM can have a wider range of skin and immune problems than the name suggests.

The 2025 editorial in Annals of Medicine and Surgery describes WHIM as an autosomal dominant disorder caused by gain-of-function mutations in the CXCR4 receptor. CXCR4 and its partner molecule CXCL12 control the release of white blood cells from the bone marrow. In WHIM the signalling is too strong, so mature neutrophils stay in the marrow, producing a low neutrophil count in the blood (neutropenia) and sometimes low lymphocyte counts as well.

Because the pattern is autosomal dominant, an affected parent has a one in two chance of passing the variant to each child. The same source says about one-third of cases are sporadic, arising without a family history, and that some people with typical features have no CXCR4 mutation found.

According to the editorial, children typically present with recurrent bacterial infections, including sinusitis, ear infections and pneumonia, and hearing loss and bronchiectasis can develop as complications. Growth and development remain normal. Other infections can include meningitis, gum infection and cellulitis. Warts caused by the human papillomavirus are the most common manifestation and are often found on the back of the hands but can also occur on the genital skin and mucosa.

The NIH skin study of 45 genetically confirmed patients found HPV infection of the skin in 76 per cent, bacterial skin infection in 71 per cent, other viral infection in 60 per cent and fungal infection in 56 per cent. It also found inflammatory skin conditions such as eczema and psoriasis, and that 16 per cent of the cohort had skin cancer despite a young median age, all with CXCR4 truncation mutations. These figures come from one US cohort and may not reflect every individual's experience.

Diagnosis is challenging because the condition is so rare and the features can overlap with other immune and blood disorders. The editorial says confirmed diagnosis requires CXCR4 gene sequencing, which usually finds a change affecting the receptor's intracellular tail. Blood counts typically show neutropenia with low lymphocytes, and immunoglobulin levels may be low.

The NIH study notes that newborn screening for severe combined immunodeficiency, which measures T-cell receptor excision circles, may reveal low levels in newborns with WHIM and could serve as an early indicator. Because diagnosis is genetic, families with an affected member can discuss testing for relatives with a clinical immunology or genetics service.

The editorial says WHIM syndrome has traditionally been treated with intravenous immunoglobulin, which gives passive immunity to counter low antibody levels, and with filgrastim (granulocyte colony-stimulating factor), which stimulates neutrophil release. These treatments have limited efficacy, require frequent administration and are costly and burdensome.

Mavorixafor, a small-molecule CXCR4 blocker, was approved by the US FDA in 2024. In a phase 3 trial of 30 participants over 52 weeks, mavorixafor increased absolute neutrophil count and reduced the annual rate of infections compared with placebo, according to the editorial. The sources read for this guide are not UK sources and do not describe its availability on the NHS, so anyone considering it should discuss licensing and access with a UK clinical immunologist.

Care is typically led by a clinical immunology team, often with haematology, dermatology and, where hearing or lung complications develop, ENT and respiratory input. Because warts can be persistent and HPV-related skin changes can progress, regular skin checks are sensible, particularly given the cancer findings in the NIH cohort.

The sources read for this guide do not cover day-to-day infection or vaccination advice in detail, so follow the plan agreed with your immunology team. Genetic counselling can help when planning a family.