It all starts with a mutation on the X chromosome.
X-linked genetic conditions are caused by mutations, or pathogenic variants, on the X chromosome. Since males typically have one X chromosome (XY), if they have a pathogenic variant on their X chromosome they usually develop the associated condition. Females, on the other hand, typically have two X chromosomes (XX), so if they have a pathogenic variant on one of their X chromosomes, they may or may not have symptoms of the associated condition.
Whether or not a female with an X-linked pathogenic variant has symptoms is determined by multiple factors, including underlying disease mechanisms and X-inactivation. X-inactivation is a phenomenon that occurs when the body randomly inactivates one of the X chromosomes in females. Most of the time, half of the cells will inactivate the mutated chromosome, and the other half will inactivate the healthy chromosome, leaving approximately equal numbers of healthy and unhealthy cells. However, sometimes by chance inactivation of the healthy chromosome can happen more often than inactivation of the mutated chromosome.
Depending on the condition, females may be referred to as carriers, asymptomatic carriers, symptomatic carriers, manifesting carriers, women with X-linked condition, females with X-linked condition, or patients. Females may also have terminology preference based on their own personal health and experiences.
X-linked conditions are usually inherited, but can also result from spontaneous mutations during development of an embryo. Females with an X-linked condition, sometimes known as “carriers,” have a 50% of passing the pathogenic variant down to their children. This means a son will have a 50% chance of inheriting the condition and a daughter will have a 50% of inheriting the mutation that may or may not cause symptoms. The symptoms of a daughter who has inherited the mutation may be different from the carrier mother. As is the case for X-linked diseases, only one parent must have or carry a condition for it to be passed down to a child.
Males can pass down their mutations, too.
When a male has an X-linked condition, the inheritance is a little more straightforward. Since males pass their one X chromosome to any daughters they have, all the daughters of a male with an X-linked condition will inherit the mutation. A male with an X-linked disease cannot pass the condition down to a son, as sons inherit the Y chromosome from their fathers.
Connect with others like you in our Facebook support group.
Remember The Girls runs a private Facebook group with over 1,300 members impacted by more than 40 X-linked conditions and from more than 30 countries in the world. Join our online community of females impacted by X-linked conditions to seek and provide support, ask questions, find resources, and learn how to advocate.