Duchenne muscular dystrophy is inherited in an X-linked pattern. Because the DMD gene sits on the X chromosome, and males have only one X chromosome, a single altered copy is enough to cause the full condition in a male. Females have two X chromosomes, so a female carrying one altered copy alongside one working copy is usually not significantly affected, though as discussed below some do develop symptoms. In rare instances, a female can have the full, classic DMD picture rather than milder carrier symptoms. This can happen when she has lost or rearranged her second, working X chromosome, when she has inherited an altered copy of the gene from both parents, or when the working copy of the gene happens to be switched off in most of her muscle cells through a process called skewed X-inactivation, in which one of the two X chromosomes in each cell is normally silenced at random but can, in some individuals, be silenced non-randomly in a way that favors the altered copy.

In approximately two-thirds of individuals with DMD who have no other affected family members, the mother is a carrier of the genetic change, even though she has no symptoms herself. In the remaining cases, the genetic change arose new in the affected individual, called a de novo change, and is not present in either parent’s blood cells.
A carrier mother has a fifty percent chance, in each pregnancy, of passing the altered gene copy to a child. A son who inherits it will be affected with DMD. A daughter who inherits it becomes a carrier herself and may, in a minority of cases, develop some degree of muscle weakness or heart involvement of her own. Even when a genetic change appears to be de novo, meaning it cannot be detected in the mother’s blood sample, there remains a fifteen to twenty percent chance that she carries the change in only a portion of her eggs, a situation called germline mosaicism. This means her other children still carry some increased risk of being affected, even when her own testing looks negative.
Because of the implications for future pregnancies and for other family members, molecular testing of the mother, and genetic counseling for the wider family, is recommended once a genetic change is identified in an affected individual. Once the specific family variant is known, prenatal testing and preimplantation genetic testing become available for future pregnancies.