Wiskott-Aldrich syndrome

Wiskott-Aldrich syndrome is a condition that affects blood cells and cells of the immune system. This condition is seen almost exclusively in males. Individuals with this condition have microthrombocytopenia, which is a decrease in the number and size of blood cells involved in clotting (platelets). This platelet abnormality, which is typically present from birth, can lead to easy bruising or episodes of prolonged bleeding following minor trauma. Eczema, an inflammatory skin disorder characterized by abnormal patches of red, irritated skin, often occurs in people with this condition. Affected individuals also have an increased risk of infection due to dysfunction of many types of immune cells, such as T cells, B cells, dendritic cells, and natural killer cells. Some people develop autoimmune disorders, which occur when the immune system malfunctions and attacks the body's tissues and organs by mistake. The risk of developing some types of cancer, such as cancer of the immune system cells (lymphoma), is increased in people with Wiskott-Aldrich syndrome.

The estimated incidence of Wiskott-Aldrich syndrome is between 1 and 10 cases per million males worldwide.

Mutations in the WAS gene cause Wiskott-Aldrich syndrome. The WAS protein (WASP) is found in cells made from hematopoietic stem cells, including blood cells and certain immune cells. This protein is involved in relaying signals from the cell surface to the actin cytoskeleton, which is a network of fibers that make up the cell's structural framework. The actin cytoskeleton has several critical functions, including determining cell shape and allowing cells to move.

WAS gene mutations impair WASP's role in cell signaling and disrupt the function of the actin cytoskeleton in certain immune cells and blood cells. Immune cells that lack WASP function tend to have trouble responding to factors that trigger cell growth and division (proliferation). Additionally, these defective cells have problems with cell movement (motility) and difficulty attaching to other cells (cell adhesion). These disruptions in normal immune cell function contribute to eczema and the increased risk of infection, autoimmune disorders, and lymphoma associated with this condition. Impaired WASP function also interferes with normal platelet development, causing microthrombocytopenia, the characteristic sign of Wiskott-Aldrich syndrome.

Read more about the WAS gene.

This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.