Genetics Northern California

X-linked Dominant

"X-linked” means that the involved gene is found on the X chromosome. Genes give the body the instructions it needs for growth and healthy development. They come in pairs and a baby receives one copy of each gene from the mother and one from the father. Chromosomes are the structures that house all of the genes. Each person has 23 pairs of chromosomes and each chromosome contains thousands of genes. The last pair is named with letters (X and Y). These two determine a person's sex (XX = female; XY = male). In X-linked dominant conditions, the altered gene is on the X chromosome. Everyone has some genes that have the potential to cause serious disease. Whether they do or not is beyond human control. There is nothing any parent can do to cause or prevent a change in a gene.

"Dominant" means that if an non-working copy of the gene is paired with a working copy of the gene, the single working gene is not enough to prevent the disease. So, a person with one non-working copy of a gene will have the disorder.

Everyone has at least one copy of the X chromosome. Men are XY and women are XX. When they have a child, the mother always gives an X, but the father can give either an X or a Y. If the child gets an X from her father, she is an XX (female). If the child gets a Y from his father, he is an XY (male).

When the altered gene is found on the X chromosome, boys can inherit it from their mothers only. Girls can inherit it from either their mother or their father. The parent who has the altered gene is called a "carrier."

Since the altered gene is the “dominant” gene, having only one copy will cause the disorder. However, the "non-dominant" gene also plays a role. In the case of girls, the "non-dominant" X can help limit the severity of the disorder. However, boys do not have a second X chromosome. Their other chromosome in this pair is the Y and Y’s do not have most of the genes that the X does. Therefore, boys do not have a copy of the functioning gene to balance out the effects of the altered gene. This is why boys are usually more severely affected.

Nevertheless, for both boys and girls, there is variation in severity depending on how severe the malfunction of the "dominant" X is. If the malfunction is mild, the person may have only a partial enzyme deficiency. The better the enzyme works, the milder the disorder. Each case is different, but for boys, the cases of more severe enzyme deficiency or complete lack of the enzyme often result in death. Yet, boys with partial enzyme deficiency can survive.

The severity of the disorder in girls varies quite a lot, depending on (1) how severely altered the "dominant" X is and (2) how well the "non-dominant" X can "balance out" the "dominant" X. Sometimes girls are diagnosed very early in infancy, others not until late adulthood, and some are never diagnosed.

Since boys are more likely to be severely affected, they often are not able to have children and pass on their altered X. As a result, the altered "dominant" X usually comes from the mother. Since the mother has two X’s, one functioning and the other altered, she may pass on either one. This means that there is a 50% chance, with each pregnancy, that the altered X will be passed on. It is important to understand that the risk of passing on the altered X will always be 50%, regardless of how many affected or unaffected children she has previously had. For example, a mother with a altered X who has had two affected children has the same chance in her third pregnancy of having an affected child as a mother with a altered X who has two unaffected children. The risk is always 1 in 2 (50%).

If the father has the altered "dominant" X and is able to have children, only his daughters will be affected. This is because he has only one X to give, and it is the altered one. If he gives his Y, the child will be a boy. Of course this boy will have an X as well, but it would come from his unaffected mother, so he would be unaffected too.

While the altered "dominant" X usually comes from the "carrier " parent, the severity of the disorder in the child may be quite different than the severity of the disorder in the parent. For instance, a mildly affected parent may have a severely affected child.