How Fragile X Syndrome is Inherited

Genes

Each cell in the human body contains thousands of genes. Genes determine many things about the person. For example, what the person will look like and whether he or she is likely to have certain illnesses. In addition, genes have instructions for making proteins in the cells. Proteins are needed for the body to work correctly.

FXS is caused by a change in the fragile X mental retardation 1 (FMR1) gene. The FMR1 gene makes a protein called fragile X mental retardation protein (FMRP) that is needed for normal brain development.

Chromosomes

Genes are found on chromosomes. Every human cell contains 23 pairs of chromosomes. People get their chromosomes from their parents. People get one of each pair of chromosomes from their mother and one of each pair from their father. The chromosomes that form the 23rd pair are called the sex chromosomes. They decide if a person is male or female. Females have two X chromosomes (XX), and males have one X and one Y chromosome (XY).

The FMR1 gene is on the X chromosome.

DNA

The chromosomes and genes have a special code called DNA. DNA has four chemical letters, called “bases”: A, C, T, and G. The order of the letters determines the information carried in each gene, like the way that a specific pattern of letters makes up the words in a sentence.

How FXS is Inherited

There is a place in the FMR1 gene where the DNA pattern CGG is repeated over and over again. In most people, the number of repeats is small (5 to 44 repeats), which is normal. If the number of repeats is too large (more than 200 repeats), the gene turns off. When the gene is turned off, no protein is made. Without the protein, the person develops FXS. This is called a “trinucleotide repeat disorder.” People get (inherit) the disorder from their parents.

Normal: 5 to 44 Repeats

Most people have about 5 to 44 repeats of the letters CGG in their FMR1 genes. This is considered a normal number of repeats. People with a normal number of repeats do not have FXS and are not at risk for having children with FXS.

Intermediate: 45 to 54 Repeats

People who have an intermediate number of repeats (about 45 to 54) do not have FXS. However, they may have a slightly higher chance of having some symptoms.

Premutation: 55 to 200 Repeats

People who have a premutation (about 55 to 200 repeats) do not have FXS. However, they might have another fragile X-associated disorder and related concerns. In addition, people with a premutation can have children with a premutation or full mutation (FXS).

• With each pregnancy, women have a 50% chance of passing the premutation or full mutation on to their child (daughters or sons). The more CGG repeats the mother has, the more likely her child will have full mutation fragile X.
• Men will have daughters with a premutation, but sons will not be affected.

Full Mutation (FXS): More than 200 Repeats

People with a full mutation (more than 200 repeats) have FXS.

• With each pregnancy, women have a 50% chance of passing fragile X on to their child (sons or daughters).

Learn more about the genetics of FXS