THE INHERITED FRAGILE X SYNDROME

Article Contents

What is Fragile Syndrome

Fragile X syndrome (FXS) is a well known and prevalent genetic condition which mainly causes a whole range of developmental problems mainly including cognitive impairment and learning disabilities. It is also referred by other names like FRAXA syndrome, marker X syndrome, Martin-Bell syndrome, X-linked mental retardation and macroorchidism. It is one of the most common inherited causes of intellectual disability after Down syndrome. FXS is always inherited either by an affected family member or a carrier in a family tree.

History of Fragile Syndrome

Martin and Bell in 1943 observed sex linked mental retardation without dysmorphic features affecting both males and females in a family. Lubs also after 36 years found a marker X chromosome in some males who were mentally retarded. Later in seventies, combination of X linked macroorchidism and mental retardation was also found out. Afterwards many clinical characteristics were also recognized. In 1991, the Fragile X Mental Retardation (FMRl) gene which was recognized to be involved in the FXS was identified. With the availability of new technologies various other important contributing factors has been identified till now.

Prevalence of FXS

Males are said to be more severely affected by FXS than the females. Approximately 1 among 3-4 thousands males and 1 among 4-6 thousands females on an average are said to be affected by this. Since it is an inherited syndrome a child can get FXS from his/her mother. One-third of the females affected are intellectually disabled whereas the males are generally mild and moderately intellectually disabled. It is also a major cause of autism worldwide.

Signs and Symptoms

The general signs and symptoms of FXS are as follows:

Mild to severe range of Intellectual disabilities.
Unstable mood and anxiety
Problems related to sensory integration, for example hypersensitive to bright lights or loud noises.
Behaviors specific to autistics are also seen for example least eye contact and hand flapping.
Delay in the speech with major affect on expressive language.
About one- fourth of the people with FXS also get affected by seizures.

Diagnosis

There is a standard test which is highly used for the diagnosis of FXS in an individual which is known as FMR1 DNA Test which is also called as Fragile X DNA Test. The main function of this test is to locate an expanded mutation in specific FMR1 gene. This type is testing is the most reliable one with 99% chances of detecting the individuals affected with FXS and which are the potential carriers of this FXS. The three general circumstances which should be considered while conducting a Fragile X testing are as follows:

If there are any clinical symptoms present which indicate the prevalence for the FXS.
If there is any family history of FXS or autism of unknown cause or learning disabilities.
If there is any personal history or family history of someone being a potential carrier of FXS.

Further specific considerations for testing are as follows:

•Any male or female should be tested if they have any cognitive disabilities, speech and language delay, developmental delay, learning disabilities or autism of unknown cause.

•Any female which face premature ovarian failure, irregular menstruation cycle or primary ovarian insufficiency.

•Any adult who is above 50 years along with a family history of FXS and also shows tremors, cognitive decline, memory loss, or personality change.

Prognosis

It has been seen that the life expectancy of the people diagnosed with FXS is very much normal like the other people. The participation of the affected people is very much active. The affected people also sometimes get other health issues like infections and seizures. The advancement in the technology along with the increase in the awareness programs have made the general public as well as the affected people to have a positive outlook toward this situation and the medical checkups done early will make the situation more under control.

Treatment and Intervention

Even with the advanced technology there is not yet any cure for this FXS but there are definitely many interventions and treatments which have made the lives of the affected individuals and their families much better than the previous years. A much better progress can be made by the individuals with FXS if they are properly educated, provided with support groups and therapies. The availability of the special education services is also an important tool for the children with FXS to have better life. This education is also complemented by a variety of therapies by the trained educator so that the development of the child from one stage to the other can be more smooth and better. The supportive therapy which is for the children with FXS includes:

•Vocational training to be provided and training for early intervention is to be given.

•To treat the vision, hearing and heart problems in usual manner.

Research on FXS

There are various research foundations which are working toward the better understanding of FXS. One such leading foundation in this area is the FRAXA Research Foundation (FRAXA). The main objective of this foundation is to find out effective treatments for curing the FXS in future. They are working towards achieving their goal while eliminating the possible blockages in the way. They started with their basic funded research in the initial years when very little was known about this syndrome. Their team initially had the molecular biologists and geneticists later on; when other developments were made the neuroscientists were also added.

Conclusion

The recent developments happening in the field have made the neuroscientists to work tremendously to reach up to their goal of getting a cure for this syndrome. Till the time we don’t get any cure better diagnosis facilities need to be easily available to the masses. Effective interventions and therapies need to teach to the educators and the youth for better handling the people affected with FXS. Awareness programs need to conducted so that the life of the people affected and non-affected can be made much better for a bright future. Support groups can also play an effective role.

References

Fragile X Research Foundation: https://www.fraxa.org

American College of Medical Genetics and Genomics Guideline (PDF): http://www.acmg.net/PDFLibrary/Fragile-X-Carrier-Testing.pdf

Emory University School of Medicine: Fragile X Syndrome (PDF): http://genetics.emory.edu/documents/resources/factsheet47.pdf

Emory University School of Medicine: Fragile X Pre-mutation—a Cause of Premature Ovarian failure (PDF): http://genetics.emory.edu/documents/resources/factsheet46.pdf

US National Library of Medicine: Encyclopedia: Fragile X Syndrome: https://medlineplus.gov/ency/article/001668.htm

Kennedy Krieger Institute: https://www.kennedykrieger.org/patient-care/conditions/fragile-x-syndrome

MalaCards: Fragile X Syndrome: https://www.malacards.org/card/fragile_x_syndrome7.