Fragile X Syndrome (FXS) is a disease that leads to intellectual disability (the leading genetic cause of autism spectrum disorder) and is prevalent in the Ashkenazi Jewish population.
What causes FXS? The fragile X is due to genetic changes in a gene called FMR1. This gene makes a protein (called FMRP) which is needed for typical brain development. Individuals who have FXS do not make this protein. In the FMR1 gene, there is a section of the DNA pattern, CGG, that is repeated many times. A small number of repeats (5 to 44) is normal; however, the following occurs as the number of repeats increase:
- 45 to 54 repeats: Those within this range of repeats are called intermediate carriers and do not have FXS. Their offspring are not at risk for FXS, but future generations may be at risk.
- 55 to 200 repeats: Those within this range of repeats are called premutation carriers. They do not have FXS but have a premutation. Premutation carriers have an increased risk for adult-onset symptoms, such as tremor-ataxia syndrome, premature ovarian insufficiency, and neuropsychiatric disorders. A woman within this range of repeats has a 50% chance of passing the premutation or full mutation on to their daughter or son. A man within this range will have a daughter with a premutation, but his son will not be affected.
- 200+ repeats: Individuals with 200+ repeats have a full mutation and therefore, have FXS.
Children of any sex can have FXS and its associated symptoms; however, the symptoms are often more severe in males. Since females have two X chromosomes, the working copy of the FMR1 gene can compensate for the inherited non-working FMR1 gene copy. This means that although they may have FXS, their symptoms are often not as severe. However, males only have one X chromosome, so if they inherit a non-working copy, they do not have another gene to compensate for the mutated one and will have more severe symptoms.
For men who are carriers of FXS, the disorder tends to skip generations. When a father passes the premutation on to his daughter, she can become a carrier and her children can inherit the disorder. Unlike men, for women who are carriers, their mutation can expand and get bigger with each generation.
Anyone considering FXS testing should consult with a genetic counselor. A diagnosis of FXS can provide an explanation for a child’s behavioral problems and allow a family to obtain treatment for the child to reach their full potential. Although there is no cure, there are options such as medication, therapy, and other treatment/support that a genetic counselor can help advise.
Written by Lilli Arbetter; Updated by Scott Weissman