Fragile XE syndrome

What causes Fragile XE (FRAXE) syndrome?

FRAXE is a genetic disorder caused by mutations in the AFF2 gene. This gene provides instructions for making a protein whose function is not well understood. Nearly all cases of FRAXE are caused by a specific type of mutation, called a trinucleotide repeat. A trinucleotide repeat is an abnormal expansion of three repeats of our DNA building blocks (nucleotides). The repeating nucleotides in FRAXE are CCG. Normally, the involved segment of three nucleotides is repeated approximately 4 to 40 times. However, in people with FRAXE, the CCG segment is repeated more than 200 times, which makes this region of the gene unstable or fragile. As a result, the AFF2 gene is turned off (silenced), and no AFF2 protein is produced. It is unclear how a shortage of this protein leads to intellectual disability in people with FRAXE. Some people with FRAXE have a deletion of genetic material in the AFF2 gene.

People with 50 to 200 CCG repeats are said to have an AFF2 gene premutation. Current research suggests that people with a premutation do not have associated cognitive problems.

Last updated on 05-01-20

How is Fragile XE (FRAXE) syndrome diagnosed?

The diagnosis of FRAXE is made based on signs and symptoms and genetic testing to confirm either a trinucleotide repeat expansion or a deletion within the AFF2 gene.

Last updated on 05-01-20

What is Fragile XE syndrome (FRAXE) syndrome?

Fragile XE syndrome (FRAXE) is a genetic condition associated with mild to borderline intellectual disabilities with physical features differing from person to person. The characteristic features are learning difficulties, often a consequence of communication problems (speech delay, poor writing skills), hyperactivity, and a shortened attention span. Nearly all cases of FRAXE are caused by a specific type of mutation, called a trinucleotide repeat expansion, in the _AFF2 _gene, which is located on the X chromosome. A trinucleotide repeat expansion occurs when there is an abnormally large number of repeats of a specific sequence of three nucleotides (building block of DNA) within our DNA. The repeating nucleotides in FRAXE syndrome are CCG. When the number of CCG repeats is over 200, people typically have the signs and symptoms seen in FRAXE. FRAXE is inherited in an X-linked manner. Although there is no specific treatment for FRAXE, there may be ways to manage the symptoms. A team of doctors or specialists is often needed to figure out the treatment options for each person.

Last updated on 05-01-20

Clinical Research Resources

Fragile X Clinical Trials

The National Fragile X Foundation provides a state by state list of clinical trials involving fragile X-associated disorders. Click on National Fragile X Foundation to view the list.

Last updated on 04-27-20

Name: American Association on Intellectual and Developmental Disabilities 501 3rd Street NW Suite 200
Washington, DC, 20001, United States
Phone: (202) 387-1968 Toll Free: (800) 424-3688 Fax : (202) 387-2193 Url:
Name: Developmental Delay Resources (DDR) 5801 Beacon Street
Pittsburgh, PA, 15217, United States
Toll Free: 800-497-0944 Fax : 412-422-1374 Email: Url:
Name: The Society for Developmental and Behavioral Pediatrics 6728 Old McLean Village Drive
McLean, VA, 22101, United States
Phone: 703-556-9222 Email: Url:
Name: March of Dimes 1275 Mamaroneck Avenue
White Plains, NY, 10605, United States
Phone: 914-997-4488 Toll Free: 888-663-4637 Fax : 914-997-4763 Email: Url:

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The RareGuru disease database is regularly updated using data generously provided by GARD, the United States Genetic and Rare Disease Information Center.

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