A female has two copies of the FMR1 gene, one on each of her two X chromosomes. The group a female is in normal, intermediate, premutation, or full mutation, as shown below is based on her FMR1 gene copy with the greatest number of CGG repeats.
A male has only one copy of the FMR1 gene on his only X chromosome, so the group a male is in is based on the number of CGG repeats in that one copy. This is considered a normal number of repeats. People with a normal number of repeats do not have FXS and do not pass a higher chance for having FXS to their children. People who have an intermediate number of repeats 45 to 54 do not have FXS and are not at risk for having children with FXS.
However, they may have a slightly higher chance of having some symptoms related to other fragile X-associated disorder s and may pass the slightly higher chance of having these disorders to their children. They do not have FXS but they might have, or may later develop, other fragile X-associated disorder s.
In addition, people with a premutation can have children with a premutation or full mutation FXS. However, the chances of having a child with a premutation or a full mutation are different for women with a premutation than they are for men with a premutation, as described below. This combined with other treatment modalities, including counseling and sensory integration therapy, can be very helpful for those who have significant behavior problems.
In addition, treatments specific for behaviors can be helpful. For example, limiting excessive sensory stimulation whenever possible may prevent aggressive outbursts and social anxiety. Working with a psychologist can help children who have tantrums, oppositional behavior, or severe hyperactivity. My child suffers from seizures. Is this common in fragile X syndrome?
The types of seizures generally seen in individuals with fragile X syndrome generally respond well to anti-seizure medication. The seizures tend to resolve by adolescence, but may continue into adulthood. If you believe your child is having seizures, an appointment with a neurologist should be scheduled as soon as possible. The neurologist may perform an EEG to determine what kind of seizures your child is having and will discuss a treatment plan with you.
My child has been referred to an ophthalmologist, but he doesn't seem to have any vision problems. Corrective lenses are generally used to treat far-sightedness and astigmatism. Treatment for strabismus often involves patching, eye exercises, or lenses to strengthen the weak eye. If none of these work, surgery may be required. I finally got my daughter potty trained, but she is still wetting herself at night. She gets upset when she wakes up. What can I do? This along with delays in potty training are frequent problems in children with fragile X syndrome.
Some behavioral tactics, such as decreasing fluids after dinner, going to the bathroom before bedtime, and waking your child to go to the bathroom when you go to bed, may help to decrease the frequency of bed-wetting. Your doctor may also be able to prescribe medications that help. I read that people with fragile X syndrome have connective tissue problems. What does this mean? Connective tissue connects and supports other tissues and includes cartilage, blood, and bone.
We're not entirely sure why individuals with fragile X syndrome have connective tissue problems. Many of these problems are minor, such as loose, flexible or hyperextensible joints.
Flat feet are also common in children with fragile X syndrome. Joint hyperextensibility tends to improve with age. Most of the time, having loose, flexible joints does not cause a problem and requires no treatment. Occasionally, however, a joint may be dislocated and will require treatment. My son with fragile X syndrome is 12 years old.
Some of the boys his age at school are starting to go through puberty. Will he go through puberty normally? Your son should go through puberty normally. This generally does not cause any complications and does not require any intervention.
However, because males with fragile X may have connective tissue problems, having large testicles may predispose them to inguinal hernias. Inguinal hernias can occur during childhood, adolescence, and adulthood. My daughter appears to be starting puberty. What should I expect? As with boys, girls seem to go through puberty normally. It is important to address your daughter's emotional status before and during her period as girls with fragile X syndrome are prone to mood swings and anxiety, particularly during times of hormonal change such as puberty and her period.
There have been a number of reports about girls having precocious puberty. Girls who present with features of precocious puberty should see an endocrinologist who may use hormone treatment to stop the progression. Will my child be able to have children? Both males and females with fragile X syndrome are fertile. Girls with fragile X syndrome are at risk for having children who also have fragile X syndrome.
Boys with fragile X syndrome are premutation carriers, even though they themselves have the full mutation. Therefore, all of their daughters will be premutation carriers. Our oldest son was recently diagnosed with fragile X syndrome.
Lancet Neurol. Neuroanatomical, molecular genetic, and behavioral correlates of fragile X syndrome. Brain Res Rev. Epub Jul Fragile X syndrome and associated disorders: Clinical aspects and pathology. Neurobiol Dis. Epub Jan Fragile X syndrome: diagnostic and carrier testing. Genet Med. FMR1 and the continuum of primary ovarian insufficiency. Semin Reprod Med. Epub Oct 3. The Fragile X premutation: new insights and clinical consequences.
Eur J Med Genet. Epub Dec 5. 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.
The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
National Center for Biotechnology Information , U. Journal List Front Neurol v. Front Neurol. Published online Jun 6. Hagerman 2, 5. Angel Belle C. Randi J. Author information Article notes Copyright and License information Disclaimer.
Specialty section: This article was submitted to Neuropediatrics, a section of the journal Frontiers in Neurology. Received Jan 18; Accepted May The use, distribution or reproduction in other forums is permitted, provided the original author s or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
This article has been cited by other articles in PMC. Abstract Fragile X syndrome FXS is the most common inherited cause of intellectual disability and the leading monogenic cause of autism spectrum disorder. Keywords: fragile X syndrome, prevalence, treatment, prevention, China.
Targeted Treatment for FXS Fragile X mental retardation 1 protein, the translation product of FMR1 , is a translational regulation factor that can control most of the proteins important for synaptic maturation and plasticity. Genetic Counseling to Prevent FXS Although CGG repeats are stable when they are in the normal range, they show genetic instability in the gray mutation or premutation regions.
Author Contributions 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.
Conflict of Interest Statement The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
Footnotes Funding. References 1. Fragile X mental retardation protein and synaptic plasticity. Mol Brain 6
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