XX Male Syndrome Health Article

Definition

XX male syndrome occurs when the affected individual appears as a normal male, but has female chromosomes. Two types of XX male syndrome can occur: those with detectable SRY gene and those without detectable SRY (sex determining region Y). SRY is the main genetic switch for determining that a developing embryo will become male.

Description

XX male syndrome is a condition in which the sex chromosomes of an individual do not agree with the physical sex of the affected person. Normally, there are 46 chromosomes, or 23 pairs of chromosomes, in each cell. The first 22 pairs are the same in men and women. The last pair, the sex chromosomes, is two X chromosomes in females (XX) and an X and a Y chromosome in males (XY).

In XX male syndrome, the person has female chromosomes but male physical features. The majority of persons with XX male syndrome have the Y chromosome gene SRY attached to one of their X chromosomes. The rest of the individuals with XX male syndrome do not have SRY detectable in their cells. Hence, other genes on other chromosomes in the pathway for determining sex must be responsible for their male physical features.

Genetic profile

In XX male syndrome caused by the gene SRY, a translocation between the X chromosome and Y chromosome causes the condition. A translocation occurs when part of one chromosome breaks off and switches places with part of another chromosome. In XX male syndrome, the tip of the Y chromosome that includes SRY is translocated to the X chromosome. As a result, an embryo with XX chromosomes with a translocated SRY gene will develop the physical characteristics of a male. Typically, a piece of the Y chromosome in the pseudoautosomal region exchanges with the tip of the X chromosome. In XX male syndrome, this crossover includes the SRY portion of the Y.

In individuals with XX male syndrome who do not have an SRY gene detectable in their cells, the cause of the condition is not known. Scientists believe that one or more genes that are involved in the development of the sex of an embryo are mutated or altered and cause physical male characteristics in a chromosomally female person. These genes could be located on the X chromosome or on one of the 22 pairs of autosomes that males and females have in common. No genes have been found to explain the female to male sex reversal in people affected with XX male syndrome who are SRY negative. Approximately 20% of XX males do not have a known cause and are SRY negative. It is thought that SRY is a switch point, and the protein that is made by SRY regulates the activity of one or more genes (likely on an autosomal chromosome) that contribute to sex development. Also there have been some studies that demonstrate autosomal recessive and autosomal dominant inheritance for the XX male.

Demographics

XX male syndrome occurs in approximately one in 20,000 to one in 25,000 individuals. The vast majority, about 90%, has SRY detectable in their cells. The remaining 10% are SRY negative, although some research indicates that up to 20% can be SRY negative. XX male syndrome can occur in any ethnic background and usually occurs as a sporadic event, not inherited from the person's mother of father. However, some exceptions of more than one affected family member have been reported.