Thus, many families in underdeveloped rural areas cannot afford the cost. This may delay treatment for FXS beyond the optimal time. Even after diagnosis, behavioral problems in children with FXS often require lifelong support, which presents a significant burden for families. Working with individuals with FXS will need the combined efforts of the family, physicians, and educational system to provide behavioral training and other management techniques.
The safety and tolerability of therapies for FXS patients are also important concerns for Chinese families. To conduct treatment for FXS patients in China, it is important to obtain the support of the government and health-care sectors and attract public attention by providing information on the importance of active treatment for FXS. Population safety and tolerability of treatment modalities should also be evaluated. Due to the above reasons, the long-term quality of life in FXS is not optimistic in China.
A study, which evaluate the outcome of Chinese patients with FXS by using social adaptive behavior to represent the quality of life, find that the adaptive behavior of children with ID is closely related to the quality of life. Compared with Down syndrome and typically developing boys, boys with FXS had significantly lower scores in the work skills, socialization and self-management, after age and receptive language ability matched.
The findings suggest that patients with FXS have much more difficulties in the life living than the other two groups. Furthermore, the level of language comprehension of Chinese FXS patients was significantly lower than that of the patients in western developed countries 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.
These females are often identified only after another family member has been diagnosed. Symptoms include intellectual disability, behavioral and learning challenges, and various physical characteristics. Males are more frequently affected, and generally with greater severity. Traditionally, a carrier of a genetic mutation is defined as a person who inherits an altered form of a gene but shows no effects of that mutation.
Premutation carriers of an FMR1 gene mutation can have no apparent signs of a Fragile X disorder, and may or may not develop FXTAS pronounced: FAKS-taz , which usually occurs in male premutation carriers after age 50, with symptoms — including balance, tremor, and memory problems — worsening with age.
Premutation carriers of an FMR1 gene mutation can have no apparent signs of a Fragile X disorder, and may or may not develop FXPOI pronounced: FAKS-poi , which usually occurs in female premutation carriers after age 40, and refers to a spectrum of impaired ovarian functions that can include infertility and early menopause.
Fragile X-associated disorders include a wide range of physical, intellectual, and behavioral symptoms that can affect family members in many different ways. Local public school systems can provide services and support for children age 3 years and older. Children can access some services even if they do not attend public school. States have created parent centers. These centers help families learn how and where to have their children evaluated and how to find services.
Having support and community resources can help increase confidence in managing FXS, enhance quality of life, and assist in meeting the needs of all family members. It might be helpful for parents of children with FXS to talk with one another. 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. It is estimated that 1 in women and 1 in men are carriers of the gene.
These people are known as 'Fragile X pre-mutation carriers'. Pre-mutation carriers may not have any symptoms of Fragile X syndrome but they are at risk of passing on the changed FMR1 gene and having a child or grandchild with Fragile X syndrome. People who are Fragile X pre-mutation carriers may also be at risk of developing health problems later in life. Around 20 per cent of female Fragile X pre-mutation carriers experience reduced fertility or early menopause.
These conditions are called Fragile X-associated Disorders. Fragile X syndrome and Fragile X-associated disorders can only be diagnosed by DNA testing — usually by a blood test but sometimes via cheek swab or mouthwash. If possible, testing should be done at a recognised genetics service. If there is a diagnosis of Fragile X syndrome, it is important that immediate and extended family members are also tested to identify others who may have the changed FMR1 gene.
This is called cascade testing. DNA testing is recommended for:. Unfortunately diagnosis of Fragile X syndrome is often delayed and it is not uncommon for families to have had a second child born with Fragile X syndrome before the first child has been diagnosed. A prompt diagnosis of Fragile X syndrome is important so that families can get access to appropriate early intervention services to help their child reach their full potential.
The facts about Fragile X syndrome are complicated and the ramifications for families can be serious. It is recommended that parents and family members ask their doctor to refer them to a genetics service, both for testing and follow-up counselling. Genetic counsellors are health professionals qualified in both counselling and genetics. As well as providing emotional support, they can help you to understand Fragile X syndrome and what causes it, how it is inherited, and what a diagnosis means for your child's health and development, and for your family.
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