46,XX testicular difference of sex development is a condition in which individuals with two X chromosomes in each cell, the pattern typically found in females, have a male appearance. People with this condition have male external genitalia. They generally have small testes and may also have other features such as undescended testes (cryptorchidism) or the urethra opening on the underside of the penis (hypospadias). A small number of affected people have external genitalia that do not look clearly male or clearly female.

People normally have 46 chromosomes in each cell. Two of the 46 chromosomes, known as X and Y, are called sex chromosomes because they help determine whether a person will develop male-typical or female-typical sex characteristics. Females usually have two X chromosomes (46,XX), and males usually have one X chromosome and one Y chromosome (46,XY).

Approximately 1 in 20,000 individuals with a male appearance have 46,XX testicular difference of sex development.

SRY-positive 46,XX testicular difference of sex development is almost never inherited. This condition results from the translocation of a Y chromosome segment containing the SRY gene during the formation of sperm (spermatogenesis). Affected people typically have no history of the condition in their family and cannot pass on the condition because they are infertile.

Published Date: September 28, 2022
Published By: National Institutes of Health