Choroideremia (CHM) Inheritance

Choroideremia (CHM) is inherited in an X-linked pattern, which means the gene responsible for the condition is located on the X chromosome.

Females have two X chromosomes. Typically, only one X chromosome carries the defective CHM gene, while the other X chromosome has a healthy copy that produces REP-1 (Rab escort protein-1). Because of this, females usually do not experience the full effects of CHM. However, many female carriers still develop changes in their eyes, which can range from mild retinal alterations to significant retinal degeneration, visual field loss, and decreased visual acuity, especially later in life.

Female carrier with signs in the eye. OCT scan of the retina of a CHM female carrier showing central thinning of the retina.

Female carriers often show “moth-eaten” or patchy pigmentation at the retinal pigment epithelium (RPE) due to lyonization. These OCT scans compare a normal retina with that of a CHM carrier, which shows central retinal thinning.

Males have one X chromosome and one Y chromosome. If their single X chromosome carries the defective CHM gene, they will be affected by the condition. Males cannot be carriers, but they can pass the gene to their daughters, who then become carriers. Fathers do not pass X-linked genes to their sons, since sons inherit the Y chromosome from their fathers.

Inheritance probabilities

Female carriers have a 50 percent chance of passing the CHM gene to their daughters (who will become carriers).
Female carriers also have a 50 percent chance of passing the gene to their sons (who will be affected).

Diagram illustrating X-linked inheritance. An affected male passes the gene to all of his daughters, making them carriers, but does not pass it to his sons. A carrier female has a 50% chance of passing the gene to each child. Male and female silhouettes are shown with arrows indicating inheritance patterns.