X-Linked Lymphoproliferative Disease

X-linked lymphoproliferative syndrome (XLP) is an immune system disorder that occurs almost exclusively in males. People with XLP have an increased risk of infection because their body cannot properly regulate the number of immune system cells (lymphocytes) and blood cells. The symptoms associated with XLP vary from person to person, and even among family members. XLP generally has two subtypes, which are caused by genetic changes in different genes: XLP1 is mainly characterized by an inappropriate immune response to Epstein-Barr virus (EBV) infection, leading to hemophagocytic lymphohistiocytosis (HLH) or severe mononucleosis; dysgammaglobulinemia; and lymphoproliferative disease (malignant lymphoma). XLP2 is usually characterized by HLH (often associated with EBV), dysgammaglobulinemia, and inflammatory bowel disease (colitis). People with XLP2 have not been known to develop lymphoma. Signs and symptoms of HLH include fever, enlarged lymph nodes and spleen, skin rashes, and problems with the lungs, digestive system, liver, and nervous system. The heart, kidneys, or other organs may also be affected. Mononucleosis may cause fatigue; fever; an inflamed and sore throat; enlarged lymph nodes, liver, and spleen; and symptoms of anemia. Dysgammaglobulinemia causes an increased risk of recurrent infections. XLP1 is caused by genetic changes in the SH2D1A gene, and XLP2 is caused by genetic changes in the XIAP gene. Inheritance is X-linked recessive. However, in rare cases, females with a genetic change on one copy of the responsible gene develop symptoms of XLP. A diagnosis of either type of XLP can be confirmed with genetic testing. Of note, there have been males with genetic changes known to cause XLP that have not developed symptoms.

Genetic Mutations: X-linked lymphoproliferative disease is caused by genetic mutations, also known as pathogenic variants. Genetic mutations can be hereditary, when parents pass them down to their children, or they may occur randomly when cells are dividing. Genetic mutations may also result from contracted viruses, environmental factors, such as UV radiation from sunlight exposure, or a combination of any of these.

If you suspect you may have this disease, you may want to start collecting your family health history. Information such as other family members who have had similar symptoms, when their/your symptoms first appeared, or exposures to any potential disease-causing environmental factors should be discussed with your medical team.

Yes. It is possible for a biological parent to pass down genetic mutations that cause or increase the chances of getting this disease to their child. This is known as inheritance. Knowing whether other family members have previously had this disease, also known as family health history, can be very important information for your medical team.

There are multiple ways, or patterns, a disease can be inherited depending on the gene(s) involved. Based on GARD’s current data, this disease can be inherited in the following pattern(s):

X-Linked: X-linked inheritance means the genetic mutation is located on the X chromosome, one of the sex chromosomes. The male sex chromosome pair consists of one X and one Y chromosome (XY). The female sex chromosome pair consists of two X chromosomes (XX). Because males have just one X chromosome, it takes only one copy of the mutated gene to cause the disease. Females that have one copy of the mutated gene may have symptoms similar to those experienced by affected males, but usually have less severe symptoms, or no symptoms at all.

Female parents with one X-linked mutated gene have a 50% chance of passing on the mutation to each of their biological children. Male parents with an X-linked mutated gene will pass on the mutation to all their female children but cannot pass the mutation on to their male children.