X-linked agammaglobulinemia is caused by inheriting a faulty gene located on the X chromosome. Humans normally have 46 total chromosomes, or 23 pairs in each cell of their body. The 23rd pair determines gender; females have two X chromosomes, and males have one X and one Y chromosome. Females can have a disease-causing gene on one of their X chromosomes, but not exhibit any symptoms of the disease; they are referred to as "carriers" for the condition. Males, on the other hand, only have one X chromosome. So if their X chromosome carries a disease-causing gene, then they will express symptoms of the disease. Carrier females have a 50/50 chance with each pregnancy to pass the X chromosome with the faulty gene to a child. If a daughter receives the gene, she will be a healthy carrier like the mother. However, if a son receives the gene, he will have X-linked agammaglobulinemia.
Carrier testing for females in the family is available through molecular genetic testing of the BTK gene in addition to prenatal diagnosis (amniocentesis or chorionic villus sampling) for pregnancies where the mother is a known carrier.
In some families, an X-linked pattern of inheritance is not present. This could be because of a small family size with few male children. But, in some cases, the agammaglobulinemia is the result of a new mutation on the child's X chromosome that was not inherited from the mother.