WHIM Syndrome: Symptoms, Causes, Treatment

What Causes WHIM Syndrome?

WHIM syndrome usually happens because of a mutation in the CXCR4 gene. This gene makes a protein that helps your cells stay healthy. If you have a mutation, the CXCR4 gene becomes more active. 

This means neutrophils, a type of white blood cell, can’t leave your bone marrow and enter your bloodstream. Your body can’t fight viruses and bacteria properly, so you get sick more often.

The gene mutation that causes WHIM syndrome is called an autosomal dominant trait. This means you only need one copy of the gene variant to get the condition. You can inherit this variant from a parent, or it may happen on its own.

Is WHIM syndrome contagious?

A gene mutation causes WHIM syndrome, so it’s not contagious. If you have WHIM syndrome, you have a 50% chance of passing it on to each of your children. The risk is the same regardless of the child's gender.

How Is WHIM Syndrome Diagnosed?

There’s no one specific test that diagnoses WHIM. Your doctor will make a diagnosis based on a number of things, including a physical exam, a patient history (like how often you’ve had viral or bacterial infections and/or warts), and various blood and genetic tests.

Tests for WHIM syndrome

Your doctor will most likely order the following tests to screen for WHIM syndrome and rule out other immune system disorders:

Complete blood count (CBC). Most people with WHIM syndrome have normal red blood cells and platelets, but low levels of the white blood cells neutrophils and lymphocytes. Since these can be naturally lowered when you’re sick, your doctor will want to do a CBC when you are well.  

Immunoglobulin G (IgG) blood test. This is a test to look for the most common type of antibody in your body that fights bacterial and viral infections. People with WHIM syndrome often have low levels.

Bone marrow biopsy. In this test, a small sample of marrow is taken from one of your bones and checked under a microscope. Your doctor looks for signs of myelokathexis, a condition where mature neutrophils get stuck in the bone marrow instead of entering your bloodstream. It’s often a clear sign of WHIM syndrome.

Genetic testing. Your doctor will run a test called the primary immunodeficiency panel, which looks for a number of genetic conditions, including WHIM syndrome. This test looks for changes in the CXCR4 gene linked to WHIM.

What to know when you’re first diagnosed

An early diagnosis of WHIM syndrome can lower the risk of complications like hospital stays, hearing loss, and lung damage. It also helps you take steps to stay as healthy as possible.

Because WHIM syndrome is rare and often misdiagnosed, it's a good idea to learn all you can about it.  Here are some resources to help you learn more about the condition and find doctors with experience with it:

WHIM Syndrome. Shares resources and patient stories for people living with WHIM

International Patient Organization for Primary Immunodeficiencies. Offers brochures and webcasts to help you learn more

The Immune Deficiency Foundation. Explains WHIM syndrome and helps you find a doctor

The Jeffrey Modell Foundation. Provides information and helps you find a specialist near you

Your WHIM Syndrome Care Team

It can take a whole village of health care professionals to treat WHIM syndrome. Here’s a look at who may be on your  team. 

• Primary care provider or pediatrician to manage day-to-day medical needs, including physicals, vaccines, and sick visits
• Immunologist to help you manage your WHIM syndrome
• Hematologist, or blood doctor, to monitor your white blood cells
• Dermatologist, or skin doctor, to treat chronic skin infections and warts
• Ear, nose, and throat (ENT) doctor to manage chronic ear infections and/or hearing loss
• Dentist for gum and tooth infections
• Pulmonologist, or lung doctor, for lung infections
• Mental health professionals, like a psychologist or licensed social worker, to provide support as you live with WHIM syndrome

WHIM Syndrome Treatment

Treatment of WHIM syndrome includes both managing the immune condition and treating complications like frequent infections, hearing loss, and warts. 

Medications for WHIM Syndrome

There are several medications your doctor may recommend to treat WHIM syndrome:

Xolremdi. The FDA approved this drug in April 2024 for people 12 and older with WHIM syndrome. It opens the CXCR4 pathway, helping white blood cells leave the bone marrow and enter the bloodstream. It may lower the risk of infections by about 40%.

G-CSF therapy. This is an injected medication that helps your bone marrow produce more infection-fighting white blood cells. 

IgG replacement therapy. It helps to strengthen your immune system because it raises antibody levels. Like G-CSF, it’s given as an injection either monthly or every one to four weeks, depending on how it is given (into a vein or a shot under the skin).

Antibiotics. Your doctor will prescribe these when you have a bacterial infection like pneumonia, a skin infection, or a urinary tract infection. 

Surgery for WHIM Syndrome

If you get warts on any part of your body, you may need surgery to remove them. You’ll see a dermatologist for this. Other ways to remove them include: 

• Cryosurgery to freeze off warts
• Electrosurgery to burn them off
• Laser treatment
• Chemical peels
• Creams like fluorouracil (Efudex) or imiquimod (Aldara) to remove warts

What Are the Complications of WHIM Syndrome?

Along with frequent viral and bacterial infections, the condition can also cause more serious complications: 

Pneumonia

For some people, respiratory infections can turn into pneumonia. If this happens often, they may get bronchiectasis, a widening of the lung’s airway tubes that can cause permanent damage.

Warts

Almost 80% of people with WHIM syndrome get widespread warts caused by HPV by the time they’re 30.

Cancer

Some research shows that about 23% of people with WHIM syndrome get cancer by age 40. Most of these cancers affect the genital and anal areas and are linked to the human papillomavirus. Some people with WHIM syndrome may also have a higher risk of getting lymphoma from the Epstein-Barr virus.

Organ damage

If WHIM syndrome goes untreated, it can lead to chronic lung inflammation and/or hearing loss.

 Living With WHIM Syndrome

A healthy lifestyle can help you manage WHIM syndrome symptoms and handle daily life more easily. Here are a few things to remember.

WHIM syndrome diet

There’s no special diet you should follow if you have WHIM syndrome. Just follow an overall healthy eating pattern to keep your immune system as healthy as possible. To keep your body strong:

• Cook with healthy oils like olive or canola oil. 
• Eat plenty of fruits and vegetables of all colors. 
• Choose whole grains like whole-wheat bread, whole-grain pasta, and brown rice instead of refined grains like white rice and bread.
• Focus on healthy sources of protein like fish, poultry, beans, and nuts instead of red meat, cheese, and processed meats like cold cuts. 

This way of eating reduces inflammation and may help lower the risk of viral infections like COVID-19.

WHIM syndrome and exercise

Regular exercise keeps your body strong and helps boost your immune system. Choose activities you enjoy, like swimming, biking, running, walking, or strength training.

If your child has WHIM, having them take part in organized sports may help them feel like they aren’t different from their peers, even if they do sometimes get sick more easily. 

How is WHIM syndrome managed? 

If you have WHIM syndrome, it’s important to take steps to reduce the risk of getting an ear, respiratory, or skin infection. Here are some things you can do:

• Avoid crowds. The more people that are around you, the more likely you are to get sick. If you do end up in a crowd and you’re inside, wear a mask.
• Wash your hands often.
• Make sure all your vaccines are up to date. Ask your doctor about vaccines for pneumococcal disease, shingles, RSV, flu, and COVID. Because people with WHIM syndrome have weaker immune systems, it also helps if your loved ones stay current on their vaccines.

Support for WHIM Syndrome

You can find support from others who understand your experience with WHIM. Ask your doctor about local support groups or explore other ways to find encouragement and connection.

Global Genes RARE Portal. An online community for patients and caregivers

WHIM Syndrome Community on Facebook. A space to connect with others living with the condition and find support

Immune Deficiency Foundation. Offers communities for patients and caregivers

What Is the Prognosis for WHIM Syndrome?

Since so few people are diagnosed with WHIM, it’s hard to know what the long-term outlook is. Most people with WHIM live well into adulthood. One study of patients with WHIM syndrome found that 27% had permanent lung damage from repeated pneumonia, and 16% got cancer due to HPV infection. The earlier you’re diagnosed, the better your prognosis is.

Can WHIM syndrome be cured?

There’s no cure for WHIM syndrome right now. But there are medications to help boost your white blood cell count so that you can better fight off viruses and bacteria. Researchers have reported that one patient had no more signs of the disease after treatment with a hematopoietic stem cell transplantation (HSCT). But we need much more research.

Takeaways

WHIM syndrome is a very rare genetic disease that keeps your body’s immune system from working properly. If left untreated, it can lead to frequent viral and bacterial infections as well as warts, hearing loss, lung damage, and sometimes cancer. The earlier you’re diagnosed, the better your prognosis. If you  constantly have infections, such as respiratory, skin, and ear infections, see your doctor. If your bloodwork reveals low white blood cell levels, you can have a genetic test to confirm you have the gene mutation that causes WHIM. While there's no cure, treatment can boost your body’s white blood cell count and strengthen your immune system.

WHIM FAQs

What causes WHIM syndrome?

A change, or mutation, in the CXCR4 gene causes WHIM syndrome. This gene makes a protein that helps keep your cells healthy. The mutation results in white blood cells called neutrophils being trapped in your bone marrow, so they can't reach your bloodstream.

Can WHIM syndrome be prevented? 

There's no way to prevent WHIM syndrome, since it's caused by your genes. A healthy lifestyle may help to keep your immune system strong, which reduces your risk of infections. If you have WHIM syndrome, you should get the HPV vaccine to protect yourself against that virus and stay current on all recommended vaccines.

What are the symptoms of WHIM syndrome? 

People with WHIM syndrome often have frequent respiratory, ear, or skin infections, recurring warts, and low white blood cell counts.

Is there a cure for WHIM syndrome?

There’s currently no cure for WHIM syndrome. Medications are available to boost your white blood cell count so you can better tolerate infections.

Can WHIM syndrome affect children?

WHIM syndrome can affect children. Early signs include frequent respiratory infections, including ear infections, that can sometimes turn into pneumonia.

What kind of doctors treat WHIM syndrome?

An immunologist usually treats WHIM syndrome. You may also see your primary care provider or pediatrician, and sometimes a dermatologist, ENT specialist, or hematologist.

What’s the outlook for people with WHIM syndrome?

Most people with WHIM syndrome live well into adulthood, but they face a higher risk of complications like warts, hearing loss, lung damage, and cancer. Early diagnosis and treatment can improve their outlook.