One parent might have learned how to address some of the same concerns another parent has. Often, parents of children with special needs can give advice about good resources for these children. CDC is working to learn more about the natural history of fragile X so that better approaches to intervention can be developed.
The ORDR website provides information about National Institutes of Health-sponsored biomedical research, scientific conferences, and rare and genetic diseases. Skip directly to site content Skip directly to page options Skip directly to A-Z link. Section Navigation. Facebook Twitter LinkedIn Syndicate. What is Fragile X Syndrome?
Minus Related Pages. Signs and Symptoms Signs that a child might have FXS include: Developmental delays not sitting, walking, or talking at the same time as other children the same age ; Learning disabilities trouble learning new skills ; and Social and behavior problems such as not making eye contact, anxiety, trouble paying attention, hand flapping, acting and speaking without thinking, and being very active.
Links with this icon indicate that you are leaving the CDC website. Linking to a non-federal website does not constitute an endorsement by CDC or any of its employees of the sponsors or the information and products presented on the website. This gene is found on the X chromosome, one of the two chromosomes X and Y that determine gender. In people with fragile X, a particular section of the DNA code — CGG — is "fragile" and gets repeated an unusually large number of times, compared with the normal 5 to 50 times.
As a result, the FMR1 gene is not expressed turned on , and the body cannot produce FMR1 protein, which is related to nerve function. To continue reading this article, you must log in. Already a member? Login ». As a service to our readers, Harvard Health Publishing provides access to our library of archived content.
Please note the date of last review or update on all articles. No content on this site, regardless of date, should ever be used as a substitute for direct medical advice from your doctor or other qualified clinician. Therefore, there is a long way to go toward the diagnosis and treatment of FXS in China. Recently, an increasing number of clinicians, researchers, and the government in China are becoming aware of the significant hazards and economic burdens of rare diseases, especially chronic diseases.
Thus, the prevention and treatment of rare diseases, including FXS, has gained increasing attention. We have also begun to realize the importance of resource allocation and basic and clinical research in China. At the moment, projects on rare diseases are being implemented nationwide in China. The purpose of this promotion is to increase the study of rare diseases in China and to be in line with the world in the field of FXS Although we have begun to improve in the field of FXS, substantial gaps still exist between China and Western developed countries.
Accordingly, we should learn advanced Western technology and research methods to make progress in the testing and treatment of FXS. Additionally, coupled with the increased awareness of public and government and a significant amount of investment, China has the potential to make outstanding contributions to the diagnosis and treatment of rare diseases, including FXS. Although CGG repeats are stable when they are in the normal range, they show genetic instability in the gray mutation or premutation regions.
The premutation frequently expands to the full mutation with maternal transmission. As the length of CGG repeats increases, the risk of amplification increases. Additionally, it is influenced by the number of AGG interruptions. The AGG interruptions among the CGG repeats increase the stability of the FMR1 allele and decrease the risk of expansion to full mutations during maternal transmission.
Because of the effect of AGG interruptions on FMR1 allele stability in gray mutation or premutation regions, they should be considered when conducting genetic counseling Nolin et al. Both the number of AGG interruptions and the length of CGG repeats were associated with allele instability during maternal transmission. Maternal alleles with no AGG interruptions have the highest risk of expansion to full mutation during transmission. The results suggest that the AGG interruptions can reduce the stability of gray region and small premutation alleles with 45—69 CGG repeats during transmission.
Therefore, combined consideration of the number of AGG interruptions and the length of CGG repeats during genetic counseling will provide a more accurate risk assessment of expansion to full mutations. Recently, another study examined the stability of maternal and paternal alleles with 45—90 repeats during transmission and assessed the effect of AGG interruptions on CGG repeat instability.
Although the length of CGG repeats and the number of AGG interruptions are significant factors influencing FMR1 allele stability in the gray region and premutation alleles on transmission, other factors, such as maternal age, are likely to have a role when considering the risk of expansion to full mutation. Yrigollen et al. Interestingly, maternal age was related to the risk of expansion to full mutation during maternal transmission.
The risk of expansion to full mutation increases with age. This suggests an additive effect of maternal age and allele instability. In addition to the effects of the length of the CGG repeat and the number of AGG interruptions on stability of FMR1 alleles, maternal age is also a significant factor when considering the risk of expansion to a full mutation.
That is, a younger mother may have a lower risk of having expansion to full mutation in a child with CGG repeats. However, in the study by Nolin et al. The reason may be that maternal age has less impact on FMR1 allele stability than CGG repeats and AGG interruptions when considering the risk of expansion to full mutation.
Therefore, more evidence is needed to further demonstrate the effect of maternal age on the amplification risk of FMR1 alleles. The accurate calculated risk rate of expansion to full mutation CGG repeats will be an important information for the genetic counseling of families with individuals with FXS and premutation carriers who want to have children. A calculation model that includes the length of the CGG repeat, the number of AGG interruptions, and maternal age is more precise for genetic counseling.
Women who carry CGG repeats in premutation regions with no AGG interruptions have a risk of expansion to full mutation. Thus, these women should receive prenatal genetic counseling. Although maternal alleles with one or two AGG interruptions have lower risks than those with no AGG interruptions, they still have a risk of amplification to full mutation according to the number of CGG repeats.
If a premutation carrier can be identified in time and the appropriate measures taken, FXS can be reduced or prevented in maternal transmission to some degree. Broad screening of women during early pregnancy or among those who wish to become pregnant is considered a good approach to identify carriers with significant risk of expansion to full mutation during maternal transmission.
However, whether to accept the FXS prenatal screening should be a personal decision. Therefore, improved public awareness of FXS during early prenatal genetic screening can greatly reduce births of FXS children.
Obviously, Down syndrome is familiar to Chinese people. However, not everyone recognizes FXS. Although genetic counseling has become very advanced in Western countries, only a few hospitals and institutions can perform genetic testing for FXS in China. The main reason is that the number of CGG repeats cannot be evaluated accurately. Recently, although, some commercial FXS testing trial kits have been introduced in China, the high price and technical constraints have hindered widespread use of the kits for genetic testing and prenatal diagnosis.
Moreover, until now, the cost of genetic testing for FXS has not been covered by medical insurance in China as is screening for congenital hypothyroidism and phenylketonuria 9. The cost of genetic testing for FXS is a significant family expense, especially in underdeveloped areas. Therefore, many of FXS are underdiagnosed or misdiagnosed in clinic. At present, there is relatively scarce evidence on FXS in China, which is partly due to lack of awareness of FXS among doctors, the public, and the government.
A wide range of actively screening for FXS children is rare in China. Unless a highly clinical suspicion, pediatricians will think of this condition. It may lead to more and more FXS offspring patients in China and will make management and treatment more difficult. In addition, treatments are not always administered in the Chinese FXS population.
Most importantly, FXS treatment is a long-term supportive treatment. Once diagnosed, further medical treatment will be a substantial financial burden for a family. FXS management also brings great mental stress to the family and society. Therefore, it is critical to consider the basic national condition of China, which is still a developing country with lagging economic strength compared to developed Western countries.
Moreover, China has a very large population. The unique characteristics of China require us to provide appropriate methods for the diagnosis and treatment of FXS. First, we must improve FXS awareness among doctors, the public, and the government. Second, special guidelines should be created by Chinese language experts to guide doctors how best to describe aspects of FXS to patients.
Moreover, in the current era of network information, we should make full use of network resources to introduce basic knowledge of FXS to the Chinese public The prevention and treatment of FXS will be the result of comprehensive efforts in various arenas, including government, medical personnel, and the public. A specialized clinic and research center is an urgent necessity in order to provide the latest knowledge to Chinese medical professionals.
More publicity and education are needed to provide information and help to individuals with FXS and their families. MN contributed to conception and design, drafted the manuscript, critically revised the manuscript, and made final approval of the version to be published; YH contributed to conception and design, critically revised manuscript, made final approval of the version to be published, and agreement to be accountable for all aspects of the work; AD contributed to conception and design, critically revised the manuscript, and made final approval of the version to be published; JD contributed to conception and design and made final approval of the version to be published; HJ, QL, and RH contributed to conception and design, critically revised manuscript, and made final approval of the version to be published; JQ contributed to conception and made final approval of the version to be published; JZ contributed to conception, critically revised manuscript, and made final approval of the version to be published.
In methylation mosaicism, all the cells have a full mutation, but the methylation pattern may not be the same in all cells. Some research studies have shown that individuals with repeat size or methylation mosaicism may be less affected than those who do not have mosaicism. What is methylation? Methylation is a process in which a chemical group, called a methyl group, gets added to the DNA. When enough methyl groups are added to the DNA, the gene gets turned off.
When methyl groups are removed, the gene gets turned on. This is a normal process and many of our genes are controlled by methylation. However, in fragile X syndrome, the methylation of the FMR1 gene turns the gene off when it should be turned on. When FMR1 is turned off, its protein is not made, and you see the features of fragile X syndrome.
When someone with fragile X syndrome has methylation mosaicism, not all cells will have the FMR1 gene turned off by methylation. Some cells may have it partially turned off, and some cells may have the FMR1 gene turned on.
I heard only boys have fragile X syndrome. Why does my daughter have it also? Girls can also have fragile X syndrome even though they have two "X" chromosomes. The reason is that they have a full expansion on one chromosome and a normal repeat section in most cases on the other chromosome. The copy with the full expansion is not making any FMR1 protein, while the other copy the normal repeat section is making protein. Although some protein is being made, it may not be enough, so we can see characteristics of fragile X syndrome.
However, because some protein is being made, girls with fragile X syndrome are generally less affected than boys. Is there a cure? At this time, there is no cure for fragile X syndrome. Treatment for fragile X syndrome is provided through therapies such as special education, speech and language therapy, and occupational therapy. Medications may be helpful in managing hyperactivity, short attention span, and other behavioral or emotional problems.
In order to determine the best course of action for your child, a comprehensive evaluation is recommended. Could my brothers and sisters have children with fragile X syndrome? For moms, yes, your siblings and also your cousins are at risk for having children with fragile X syndrome. For dads, it is possible but unlikely. Why is this the case? To begin with, the repetitive region in the FMR1 gene expands through generations.
There is an intermediate expansion, called the fragile X premutation, that is about repeats in length. Individuals with a repeat length of this size are called premutation carriers and do not have symptoms associated with fragile X syndrome.
However, the premutation is unstable and can expand to the full mutation in future generations. For reasons that are not well understood, expansion typically only occurs when the premutation is inherited from the mother.
When a couple has a child with fragile X syndrome, we know that the mother is a premutation carrier as the premutation typically only expands to the full mutation when inherited from the mother. Because mom inherited the premutation from one of her parents, her siblings and cousins are also at risk for being premutation carriers and having children with fragile X syndrome.
Testing mom's parents to determine who she inherited the premutation from can tell us which side of her family is at risk for having children with fragile X syndrome. With dads, it's a little trickier. Dads can have either the normal repeat length repeats or be premutation carriers themselves. The only way to determine this is through DNA testing. In general, testing is not performed unless there is a history of fragile X in his family.
If testing is performed and dad is found to be a premutation carrier, his siblings and cousins are at risk for having children with fragile X syndrome.
If I am a premutation carrier, am I at risk for anything? Unlike many genetic disorders, being a carrier does put you at an increased risk for certain medical problems. Females who are premutation carriers are at risk for premature menopause, or loss of menses before the age of Even when occurring after age 40, the age of onset for menopause on average can occur years earlier in women who are fragile X premutation carriers.
This can be a serious concern if you are in your 30s and are planning to have another child. If you are currently trying to have a child and are having infertility problems, premature menopause could be a cause. In addition, some of the options for reducing your risk of having another child with fragile X syndrome, such as IVF with PGD, may be a less viable option due to premature menopause.
FXTAS is characterized by progressively severe intention tremor and difficulty with walking and balance.
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