What is Fragile X?

Fragile X is a family of genetic conditions, which can impact individuals and families in various ways. These genetic conditions are related in that they are all caused by gene changes in the same gene, called the FMR1 gene.

Fragile X includes:

Fragile X syndrome (FXS), the most common cause of inherited mental impairment. This impairment can range from learning disabilities to more severe cognitive or intellectual disabilities. (Sometimes referred to as mental retardation.) FXS is the most common known cause of autism or "autistic-like" behaviors. Symptoms also can include characteristic physical and behavioral features and delays in speech and language development.

Fragile X-associated tremor/ataxia syndrome (FXTAS), a condition which affects balance, tremor and memory in some older male gene carriers.

Fragile X-associated primary ovarian insufficiency (FXPOI), a problem with ovarian function which can lead to infertility and early menopause in some female gene carriers.

Some gene carriers do not exhibit any of these features.

Fragile X can be passed on in a family by individuals who have no apparent signs of this genetic condition. In some families a number of family members appear to be affected, whereas in other families a newly diagnosed individual may be the first family member to exhibit symptoms.

  Is there a cure for Fragile X?

At this time, there is no cure for fragile X syndrome. However, special education, speech and language therapy, occupational therapy and behavioral therapies are helpful in addressing many of the behavioral, and cognitive issues in fragile X syndrome. In addition, medical intervention including medications can be helpful for aggression, anxiety, hyperactivity and poor attention span. Because the impact of fragile X is so varied, it is important to do a careful evaluation of the individuals' abilities and difficulties to tailor a treatment plan to address specific needs.

  What Causes Fragile X Syndrome?

Fragile X syndrome is a genetic condition which is caused by a change in a gene that is inherited at the time of conception. This gene, called the FMR1 gene is found on the X chromosome. When this gene change occurs the FMR1 gene does not work properly. The FMR1 gene is responsible for making a protein that is important in brain development. Therefore when the gene is not working properly brain function including learning, behavior and communication is affected. The following paragraphs describe this gene change in great detail.

A short animation from the Centers for Disease Control - National Center on Birth Defects & Developmental Disabilities.

  What Tests are available to determine if someone has Fragile X?

During the 1970's and 1980's the test available for diagnosing fragile X syndrome was the chromosomal or cytogenetic test. While it was helpful, it was not always accurate. In the 1990's, two molecular DNA tests became available. These are:

The Southern Blot analysis - this determines if the gene has a full mutation and its approximate size, if the gene has been methylated and if there is mosaicism (a mixture of different cell types).

The polymerase chain reaction (PCR) analysis can determine the actual number of repeats in individuals with a normal size gene or with a premutation. It is not the test of choice to diagnose a full mutation, but is quite accurate in determining premutation and normal gene repeat numbers.

  What is the impact of Fragile X Syndrome? On Males? On Females?

Impact on males

The majority of males with fragile X syndrome will have a significant intellectual disability. The spectrum ranges from learning disabilities to severe mental retardation and autism.

In addition, males have a variety of physical and behavioral characteristics. However, no male has all of these characteristics.

Physical features such as enlarged ears, long face with prominent chin, and large testicles (in post pubertal males) are common. Connective tissue problems may include ear infections, mitral valve prolapse, flat feet, double-jointed fingers, hyperflexible joints and a variety of skeletal problems.

Behavioral characteristics in males include attention deficit disorders, speech disturbances, hand biting, hand flapping, autistic behaviors, poor eye contact, and unusual responses to various touch, auditory or visual stimuli.

Impact on females

The characteristics seen in males can also be seen in females, though females often have milder intellectual disability and a milder presentation of the behavioral or physical features.

About a third of the females have a significant intellectual disability. Others may have more moderate or mild learning difficulties. Similarly, the physical and behavioral characteristics are often expressed to a lesser degree.

  What is the difference between premutuation carriers and full mutuation carriers?


Fragile X syndrome is one of a group of conditions called trinucleotide repeat disorders. A common feature of these conditions is that the gene can change sizes over generations, becoming more unstable, and thus the conditions may occur more frequently or severely in subsequent generations. These conditions are often caused by a gene change that begins with a premutation and then expands to a full mutation in subsequent generations.

Premutations are defined as having 60-200 CGG repeats and can occur in both males and females. In males it usually does not expand to a full mutation when passed on to his daughters (A male carrier never passes on the fragile X gene to his sons as he passes on his Y chromosome to his son). A female with the premutation will often pass on a larger version of the mutation to her children. As the size of the premutation increases, there is an increased possibility that a child will receive the full mutation. Typically, the premutation has no observable impact. However, some females with a premutation will experience early menopause. (POI) Additionally, some older adults with premutations may develop a neurological condition called FXTAS (often misdiagnosed as a "Parkinson's-like" condition). Approximately 1 in 250 females and 1 in 800 males carry the premutation.

Full mutation

A full mutation is defined as having over 200 CGG repeats on the southern blot DNA test. In addition, most full mutation genes have some degree of methylation (the process which "turns off" the gene). Males with a full mutation usually have fragile X syndrome, though there is a small percentage of males with a full mutation who do not have mental retardation. About 30% of females with a full mutation have no cognitive deficits. The remaining 65-70% of females with a full mutation will have some difficulties with cognitive, behavioral, or social functioning and may have some of the physical features found in males.

  How is the Fragile X Gene passed from generation to generation?

Fragile X in an "X-linked" condition, which means that the gene is on the X chromosome. Since a woman has two X chromosomes a woman with a premutation or full mutation has a 50% chance of passing on the X with the mutation in each pregnancy. If she has a premutation, and it is passed on (to either males or females), it can remain a premutation or it can expand to a full mutation. If she has a full mutation and it is passed on (to either males or females), it will remain a full mutation. In many X linked conditions only males who inherit the abnormal gene are affected, however in fragile X syndrome females can also be affected. Additionally, in other X linked conditions all males who carry the gene are affected, however in fragile X syndrome, unaffected males can carry the gene in the premutation form and have no symptoms of fragile X syndrome. Males with the premutation will pass it on to all of their daughters and none of their sons (they pass their Y chromosome on to their sons).

  What is FMR1? Why is it called the Fragile X Gene?

Fragile X got its name because under a microscope, a portion of the X chromosome from an individual with fragile X syndrome appears "broken" or "fragile". As researchers studied this area of the X chromosome in individuals with fragile X syndrome, they found it contained more than the normal amounts of DNA. Specifically, it turned out to have a large number of repetitions of DNA called a CGG repeat. This expansion of DNA is what gives the Fragile X chromosome its unique appearance.

In May 1991, researchers identified the gene responsible for Fragile X. This gene, which is on the X chromosome, is called FMR1, which stands for "Fragile X Mental Retardation 1". (Note that most of the disability community no longer uses the term "mental retardation", instead referring to it as "intellectual disability", but that is what the gene was originally named in the scientific literature.) Every person has at least one copy of the FMR1 gene. Women have two X chromosomes, so they have two copies of the gene. Men have only one X chromosome, so they have just one copy of FMR1. The gene varies in length from one person to another. The variation occurs because there is a range of CG repeat numbers from person to person. What distinguishes people who have a Fragile X mutation from those who don't is the number of times this CG pattern is repeated.

Most of our genes either make a protein or regulate proteins made by other genes. The FMR1 gene is responsible for producing a protein that is important in brain development. This protein is called FMRP (Fragile X Mental Retardation Protein). Individuals with fragile X syndrome have a deficiency of this protein.

For more information, please visit the National Fragile X Foundation website.