WHIM Syndrome

What is WHIM syndrome?

WHIM syndrome stands for warts, hypogammaglobulinemia, infections, and myelokathexis syndrome. It is a primary immunodeficiency disorder caused by irregularities in cell development or maturation. This syndrome is very rare, with only 60 cases being reported in medical literature. 

What are the symptoms of WHIM syndrome?

Symptoms and severity vary between individuals, and the onset is usually in early childhood or infancy. Recurrent bacterial infections are a main symptom of WHIM syndrome. Some of the most common infections are middle ear infections, infections of the skin and underlying tissue, bacterial pneumonia, sinusitis, infections of the joints, dental cavities, and infections of the gums. All of these infections bring their own symptoms and complications as well. 

If there is exposure to HPV, warts will develop. They can spread to the hands, feet, face, and trunk. Mucosal, oral, and genital warts may also occur, and they have the potential to develop into carcinoma. 

Myelokathexis is another main symptom of WHIM syndrome. It happens when there are too many white blood cells present in the bone marrow. Hypogammaglobulinemia, which happens when there is a low level of antibodies, leads to a weakened ability to fight infections. 

What causes WHIM syndrome?

Multiple mutations in the CXCR4 gene cause WHIM syndrome. This gene, which is the chemokine receptor, is involved in cell trafficking. This malfunction makes the CXCR4 protein hyperfunctional.

This mutated gene is inherited in an autosomal dominant pattern, meaning only one copy has to be passed down for the disorder to be present. In some cases the malfunction is sporadic, meaning it is not passed down.  

How is WHIM syndrome diagnosed?

A clinical evaluation, examination of family and medical histories, and finding of characteristic symptoms are all used to diagnose WHIM syndrome. Blood tests and bone marrow biopsies may also be performed. A diagnosis is confirmed through genetic testing. Those who think they may have this condition may be eligible to receive free genetic testing, click here for more information. 

What are the treatments of WHIM syndrome?

Treatment for this disorder is symptomatic. A team of specialists is typically required to treat the different symptoms of this disorder. Early and aggressive treatment of infections is necessary. Granulocyte colony stimulating factor (G-CSF) or granulocyte macrophage colony stimulating factor (GM-CSF) are used for the treatment of myelokathexis. Infusions of immunoglobulins can treat hypogammaglobulinemia. Surgery can remove warts, but they are often recurrent. 

Where can I find out more about WHIM syndrome?

• NORD
• NIH
• Immune Deficiency Foundation