Fragile X Syndrome affects nearly 1 in every 4,000 males and 1 in every 6,000 to 8,000 females in the USA. Therefore, males are approximately twice as likely to develop the condition. However, females are about 4 times more likely to be carriers of the syndrome and are asymptomatic since the altered gene occurs on the X chromosome. Since males (XY) only have one X chromosome, it is more likely that they will develop the condition if there is a mutation inherited from the mother. This condition has been found to affect all races and ethnicities. 

Fragile X Syndrome is a condition that is caused by a genetic mutation in the FMR1 gene, found at Xq27.3 on the X chromosome. Generally, people who have the condition inherit a complete gene mutation, which means they have the sequence of CGG repeated around 200 times. For comparison, someone without the condition typically has 5 to 44 CGG repeats. Fragile X syndrome can be described as a spectrum, with a  “gray zone” characterized by 45 to 54 occurrences of the trinucleotide repeat. This modest increase of repeats is known as a “premutation”. However, as the gene is passed down through generations, the number of CGG repeats increases and the mutations become more pronounced until complete Fragile X syndrome manifests.

When the individual has Fragile X Syndrome, a post-translational process known as DNA methylation occurs in an abnormal way, during which the gene cannot produce the necessary FMRP protein. DNA methylation affects the creation of certain mRNA strands for particular proteins, and therefore, plays a large role in the inhibition of the creation of the FMRP protein. FMRP plays a vital role in the central nervous system, particularly in the development of neurons in the brain. Therefore, a lack of the FMRP protein results in the characteristic symptoms of Fragile X Syndrome.

In children, there are 3 main symptoms of Fragile X Syndrome. One of the main symptoms of the condition is developmental delay, including sitting, walking, and talking later than other children of the same age. Similarly, Fragile X Syndrome is often accompanied by social and behavioral problems. For example, affected children may have trouble paying attention, be hyperactive, or exhibit anxiety in social situations. In addition, the condition can be accompanied by learning difficulties. In affected males, some form of intellectual disability is rather common. Females, on the other hand, often have normal intellectual capacity. Many of the symptoms of Fragile X Syndrome are very similar to that of autism spectrum disorders. The physical symptoms of the condition, including flat feet, protruding ears, and a prominent chin and forehead, typically develop after affected males hit puberty. Females typically have less pronounced physical symptoms than males.

Fragile X Syndrome is typically diagnosed after the individual displays characteristic symptoms of the condition. From that point, doctors will conduct diagnostic tests to confirm the diagnosis.The condition used to be diagnosed through chromosome analysis, though now it is primarily diagnosed through molecular genetic testing. The condition is called “Fragile X Syndrome” since affected individuals possess an X chromosome that appears weak or broken. 
 

Tests to confirm Fragile X Syndrome diagnosis include:

• Molecular genetic testing → will allow doctors to understand how many CGG repeats in the FMR1 gene are present

• Testing to determine methylation status → evaluation of the chemical status of the FMR1 gene and the resulting production of FRMP protein

• Chromosome analysis → previous strategy conducted to diagnose the condition; less accurate and more costly than molecular genetic testing

While there is no cure for the condition currently, there are numerous treatments for Fragile X Syndrome that help alleviate symptoms associated with the condition. Some of the more common treatments involve behavioral modification programs, speech therapy, and sensory integration training. Genetic counseling is also generally recommended to the individual and their families. Often, early intervention programs are the most effective as they aid with the child’s development and allow children to accrue social skills they may otherwise lack. There are many organizations that are currently searching for a cure for the condition. FRAXA (www.fraxa.org) is an organization that is developing investigational therapies for the condition. 

Affected individuals typically have normal lifespans if they keep up a healthy and active lifestyle. However, people with Fragile X Syndrome are more prone to other medical problems that range in severity. For example, milder problems include ear infections, which are common in affected individuals. However, more serious medical issues, such as seizures, can also affect the individual. Therefore, frequent medical check-ups are necessary to ensure the health of the individual. 

Individuals with fragile X syndrome may seek help from occupational therapists, speech pathologists, and psychologists. An occupational therapist can work with individuals on hypersensitivity and tactile defensiveness. In addition to this, the therapist can give advices and assistance on calming techniques, movement, fine motor development, and oral motor development.  A speech pathologist can help with language skills and speech (such as pronunciations). A psychologist can give support on behaviour, social emotions, education, and family.

Fragile X Syndrome. Genetic Home Reference website. Available at: http://ghr.nlm.nih.gov/condition/fragile-x-syndrome 

Fragile X Mental Retardation Syndrome. Online Mendelian Inheritance in Man (OMIM) website. Available at: http://www.omim.org/entry/300624 

Fragile X Syndrome. National Organization for Rare Disorders website.  Available at: https://rarediseases.org/rare-diseases/fragile-x-syndrome/

Hagerman R. Fragile X Syndrome. OrphaNet website. Available at: http://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=908.0 Accessed May 2016.

https://fragilex.org/genetics/what-defines-a-carrier/#:~:text=Male%20premutation%20carriers%2C%20because%20they,their%20risk%20of%20developing%20FXTAS.

https://www.cdc.gov/ncbddd/fxs/facts.html