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X-linked Lymphoproliferative Syndrome

Also called: Duncan disease; Purtilo syndrome; X-linked progressive combined variable immunodeficiency

X-linked lymphoproliferative syndrome (XLP) is a rare disorder that causes the immune system to not work right. People with XLP have an increased chance of developing a severe reaction called fulminant infectious mononucleosis (FIM) following infection with Epstein Barr virus. With FIM, too many immune cells become activated. These cells build up in parts of the body, including the liver, spleen, bone marrow, and brain. This reaction is sometimes called hemophagocytic lymphohistiocytosis (HLH). Without treatment, this disorder can lead to severe organ damage and death.

People with XLP are almost always male. The condition is diagnosed in fewer than 1 out of 1 million boys or young men per year. How severe the condition is varies widely, even among members of the same family.

Types of X-linked lymphoproliferative syndrome

There are 2 types of XLP: XLP-1 and XLP-2.

People with XLP-1 develop FIM/HLH after Epstein-Barr virus infection. Normally, the Epstein-Barr virus causes a person to develop mononucleosis, or “mono.” Mono is common among children and teens. A person with mono has a sore throat, swollen glands, fever, and tiredness. They usually get better on their own. But a person with XLP-1 usually cannot fight off the Epstein-Barr virus. Instead, they are at risk to develop FIM/HLH.

People with XLP-2 are also at increased risk to develop HLH. Those with XLP-2 may develop HLH following infection with other viruses, bacteria, or fungus, not just the Epstein-Barr virus. 

Cancer risk with X-linked lymphoproliferative syndrome

About 25% (1 in 4) of people with XLP-1 will develop cancer of the immune cells, called lymphoma, during their lifetime. People with XLP-2 do not have a greater cancer risk than the general population.

Other health problems with X-linked lymphoproliferative syndrome

Those with XLP may develop other medical problems. The risk of developing these problems depends on whether a person has XLP-1 or XLP-2. Not all people with XLP develop these problems. It is not possible to predict which people with XLP-1 or XLP-2 will develop specific health problems.

People with XLP-1 may develop:

  • Lymphoma
  • Too few antibodies in the bloodstream. Antibodies are proteins that are needed to help fight infections.
  • Failure of the bone marrow to produce enough blood cells. This is called aplastic anemia.
  • Swelling of small blood vessels in the lungs, eyes, brain, or other organs

Those with XLP-2 may develop:

  • Enlarged spleen
  • Too few antibodies in the bloodstream
  • Aplastic anemia
  • Swelling of the large intestine (called colitis)
  • Swelling of small blood vessels in the lungs, eyes, brain, or other organs

Causes of X-linked lymphoproliferative syndrome

Most cells in the body have 46 chromosomes. Chromosomes are made of DNA. They contain our genes. Genes carry information that tells cells in our body how to function. Sometimes a gene becomes changed and no longer works as it should. These changes are called mutations.

Each cell has a pair of sex chromosomes called X and Y. Females have 2 X chromosomes. One copy is from their mother. Another copy is from their father. Males have 1 X chromosome from their mother and 1 Y chromosome from their father.

Because males only have 1 X chromosome, their cells contain only 1 copy of the genes that are on the X chromosome. That gene copy is from their mother. They do not inherit any copies of those genes from their father.

Mutations in 1 of 2 genes can cause XLP. Both of those genes are on the X chromosome. The gene that is affected determines whether a person has XLP-1 or XLP-2.

Diagnosis of X-linked lymphoproliferative syndrome 

Health history

A health care provider may suspect that your child has XLP after studying their medical and family cancer history.

This information helps the health care provider and the genetic counselor know if:

  • There are more cancers than normal in your family
  • These cancers happened at a younger age than expected
  • The cancers are those that are seen in X-linked lymphoproliferative syndrome

Your provider or genetics counselor may recommend SH2D1A and XIAP genetic testing if they suspect XLP.

Learn more about types of genetic tests.

Genetic testing for X-linked lymphoproliferative syndrome

A blood sample is sent to a genetic testing lab. The lab runs genetic tests that look for changes in the SH2D1A and XIAP genes.

If your child has a SH2D1A or XIAP mutation, the genetic counselor will work with your family to:

  • Find out if other family members should consider testing for a SH2D1A or XIAP mutation
  • Help your family understand the increased cancer risk from XLP
  • Give you information to help with your decisions about prenatal genetic testing

Genetic testing before or during pregnancy

Parents may choose to do prenatal testing to find out if a pregnancy is affected with a known SH2D1A or XIAP mutation. Testing may take place either before pregnancy occurs or during pregnancy.

You should work with a genetic counselor to review the pros and cons of the test. The genetic counselor can also help you prepare for the test results.

Testing before pregnancy is called preimplantation genetic testing (PGT). This special type of genetic testing is done along with in vitro fertilization (IVF). PGT tests embryos for a known SH2D1A or XIAP mutation before a provider places the embryo into the uterus.

Testing during pregnancy can help providers see if a pregnancy has a known SH2D1A or XIAP mutation. A doctor gathers cells from the pregnancy in 1 of 2 ways:

  • Chorionic villus sampling (CVS) is done during the first 3 months of pregnancy (1st trimester).
  • Amniocentesis is done after the first 3 months of pregnancy (2nd trimester or later).

After tissue collection, the lab checks the sample for SH2D1A and XIAP mutations.

Both tests carry minor risks. Discuss risks with an experienced health care provider or a genetic counselor.

Special concerns for genetic testing

Take time to think carefully about the benefits and risks of genetic testing. Speak with a genetic counselor before testing. If you decide to get tested, talk with your health care provider or a genetic counselor about your results so you can understand what they mean.

Sometimes, children or adults with XLP feel sad, anxious, or angry after getting their test results. Parents may feel guilty if they pass the SH2D1A or XIAP gene mutation to 1 or more of their children. People with a SH2D1A or XIAP gene mutation may also have trouble getting disability or life insurance.

Read more about genetic discrimination.

Treatment of X-linked lymphoproliferative syndrome 

Treatment of XLP-1 or XLP-2 depends on how severe the cause and symptoms are. Find a health care provider who knows this condition well for treatment.

Currently, the only way to cure XLP-1 is with a stem cell transplant. The transplant helps replace the unhealthy immune system with a healthy immune system from a person who does not have XLP-1. The treatment of XLP-2 may or may not require transplant.

Hemophagocytic lymphohistiocytosis (HLH) or fulminant infectious mononucleosis are often treated with immune suppressing medicines, such as steroids and chemotherapy, and medicines that block the actions of certain cytokines.

Patients may also be treated with a medication called rutiximab, which helps to lower the levels of Epstein Barr virus. For patients requiring a curative stem cell transplant, the goal of this treatment is to help a person become healthy enough to receive the transplant.

Lymphoma is treated with chemotherapy. Colitis is treated with steroids. Hypogammaglobulinemia (too few antibodies in the blood) is treated with infusions of antibodies every 3–4 weeks.

Monitoring and follow-up care for X-linked lymphoproliferative syndrome

Cancer screening

Children with XLP are not usually screened for lymphoma because the age at which it may develop can vary widely. People with the condition should watch closely for general signs or symptoms of lymphoma, including:

  • 1 or more firm or enlarged lymph nodes
  • Feeling tired
  • Fever
  • Weight loss
  • Night sweats
  • Trouble breathing

If any of these occur and do not go away, see a health care provider who knows XLP well. These could be the signs of lymphoma.

People of any age with XLP must watch for signs and symptoms of FIM/HLH. If any of these occur, seek medical help right away. Early detection and treatment give the best chances for cure.

Living with X-linked lymphoproliferative syndrome 

People with XLP should monitor their health and adopt healthy habits throughout their lifetime.

Maintain a healthy lifestyle

Habits that will help you maintain a healthy lifestyle include:

  • Eat a healthy diet with lots of fruit and vegetables.
  • Get regular exercise.
  • Avoid excess sun exposure. Always wear a hat, protective clothing, and sunscreen (SPF 30 or higher) when out in the sun.
  • Avoid unnecessary radiation exposure.
  • Avoid smoking or the use of tobacco products.
  • Avoid being around secondhand smoke.
  • Avoid excessive alcohol use.

X-linked lymphoproliferative syndrome care at
St. Jude

The St. Jude Cancer Predisposition Program is dedicated to diagnosing and screening children with a genetic predisposition for cancer. Our program offers the best clinical care possible. We engage in cutting-edge research to gain more information about genetic disorders and cancer, and to improve the care and treatment for patients who are affected by these conditions.

Our genetic counselors, clinicians, genetics nurse practitioners, and research assistants work together to provide patients with:

  • A complete health history
  • A record of cancer that happened over the past 3 generations (family tree or pedigree) to see how diseases were passed down
  • Physical exams to check for genetic disease
  • Confidential genetic counseling and testing
  • Cancer screenings for those with genetic disease to detect and treat cancer as soon as it occurs
  • Recommended cancer treatments and ways to reduce cancer risk
  • Genetic testing for immediate (1st degree) relatives

XLP increases your child’s risk for cancer. Visit Diseases Treated to learn more about how we treat specific cancer types.

Related clinical trials  

St. Jude offers clinical trials and cancer research studies for children, teens, and young adults who have cancers associated with XLP.

Learn more about clinical research at St. Jude.

GENETX: Assessing Gene Therapy Communication Needs

Study goal:

To learn more about participants beliefs, attitudes, and questions about gene therapy to help make web-based resources to share information. This could help patients make treatment decisions.


18 to 35 years old with rare genetic diseases

Published results
G4K: Genomes for Kids

Study goal:

The main goal of this study is to learn more about the reasons childhood tumors form and how to treat them better.

TBANK: Collecting, Banking, and Distributing Human Tissue Samples in St. Jude Biorepository

Study goal:

To provide a high-quality repository of tumor and normal samples to facilitate translational research performed by St Jude faculty and their collaborators

PG4KDS: Clinical Implementation of Pharmacogenetics

Study goal:

1) Test each patient for hundreds of gene variations that might be important for drug use. All of the gene test results will be in the research laboratory, but as time goes on, the study will evaluate scientific evidence and selectively move test results for a few genes into the medical record if the evidence strongly shows that the result can help in better prescribing of drugs for patients; 2) Estimate how often pharmacogenetic test results are moved from research tests into a patient’s medical record; 3) Use methods to choose which of these tests should be put in the medical record; 4) Use computer-based tools in the electronic medical record to help doctors use gene test results when prescribing drugs; 5) Share feelings and concerns of patients and their families about gene test information being put in their medical record.

SJFAMILY: Study of Cancer in Families

Study goal:

The main purpose of this trial is to learn about the genetic causes of cancer. 


Younger than 50 years old

A statue of children running and holding hands

Seeking treatment at St. Jude

Patients accepted to St. Jude must have a disease we treat and must be referred by a physician or other qualified medical professional. We accept most patients based on their ability to enroll in an open clinical trial.

How to seek treatment

Contact the Physician / Patient Referral Office

Call: 1-888-226-4343 (toll-free) or 901-595-4055 (local)  | Fax: 901-595-4011 | Email: | 24-hour pager: 1-800-349-4334


Learn More

If you have questions about the Genetic Predisposition Clinic and care for XLP, email our team at

Read more

Sources outside St. Jude