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Fragile X Syndrome

  • If your child has been diagnosed with fragile X syndrome, you may be feeling overwhelmed. Remember that seeking out information is not only necessary but empowering—it allows you to partner with your child’s care providers to make the best decisions for your child and your family.

    Many families have been down this path and learned how to help their child manage and you will, too. Here at Children’s Hospital Boston, there are lots of ways we can help.

    Fragile X is a genetic condition that can cause a range of learning and behavioral problems as well as physical issues, though these are usually less significant.

    • Some children with fragile X have mild learning disabilities, while others have severe intellectual disability.

    • Children with fragile X often have some degree of behavioral and emotional problems, such as hyperactivity, anxiety and sensitivity to sensory stimulation, including noise and touch.

    • It can affect both girls and boys, but symptoms are usually more severe in boys.

    • Fragile X is thought to occur in around 1 in 4,000 boys and 1 in 6,000 girls.

    How Boston Children’s Hospital approaches fragile X

    At Children’s Fragile X Program, we focus on two things: providing care for patients and families affected by fragile X and carrying out research designed to better understand fragile X and develop better treatments for it. We also work with adults who are premutation carriers who may be affected by, or at risk for, early ovarian failure or fragile X-associated tremor/ataxia syndrome (FXTAS) to make sure that they get the right treatment.

    Along with the multidisciplinary care offered through the Fragile X Program, our patients also have access to the broad range of resources available at Children’s, including:

    Our specialists maintain connections with all New England-based fragile X support groups. Your child and your family are in good hands here.

     

    Reviewed by: Jonathan D. Picker, MD, PhD
    © Children’s Hospital Boston, 2010

     

     

  • Understanding your child with fragile X

    Because of the alterations in the networks of cells in their brains, perceptions like sight and sound are experienced much more intensely by children with fragile X. Understandably, this colors how they react to stimuli, and they may often seem anxious.

    Children with fragile X want friends, but may withdraw to protect themselves. And while they don’t want to hurt anyone, they might sometimes be aggressive, as a way of defending what they perceive to be a zone of safety around them.

    As with all kids, children with fragile X have interests and things that excite them, but it may take some effort and patience to find out what they are, because they may be afraid to express it.

    Why are girls often less affected by fragile X than boys?

    Since boys only have one X chromosome, they only have one FMR1 gene. If it’s not working, there’s no backup. Females have two FMR1 genes, so if one gene has the full mutation, it’s likely that the other still works. If the gene doesn’t work perfectly, she may show some symptoms of fragile X.

    Are there medical concerns associated with fragile X?

    Unlike many other genetic conditions, fragile X syndrome does not cause many medical complications. Health problems in children with fragile X may include:

    As the children become adults, they may also develop:

    • mitral valve prolapse (leaky heart valve); this is seen in about half of all adults with fragile X
    • high blood pressure that can be treated with medication
    • scoliosis

    Children and adults with fragile X may also have problems with their connective tissues. This leads to some of the physical characteristics, such as flat feet and low muscle tone.

    Causes

    What causes fragile X?

    The short answer is that fragile X is caused when a mutation in a gene prevents the body from making an important protein. We can look at each of these components in more detail:

    1. The gene

    Fragile X is caused by a “full” mutation in the FMR1 gene, which creates a protein called FMRP. The FMR1 gene is found on the X chromosome, which means that females (who have two X chromosomes) have two copies of the FMR1 gene, and males (who have one X chromosome) have only one.

    Genes are made out of a string of molecules called nucleotides. There are four types of nucleotides, called A, G, T and C.

    2. The mutation

    Part of the FMR1 gene is a pattern of three nucleotides that repeat themselves: CGG CGG CGG. In a normal FMR1 gene, this pattern appears between 10 and 40 times in a row. In a “full” mutation of an FMR1 gene, it appears more than 200 times. This is too many, and prevents the gene from making the protein it’s supposed to.

    Sometimes, the CGG pattern repeats itself more times than normal, but not enough for the full mutation, and not enough to stop the gene from making the protein. When this happens, the individual is said to be a “premutation carrier.” For reasons that are unclear, this premutation gene can grow into the full mutation (repeat CGG more than 200 times) in the carrier’s children, grandchildren or descendents further down the line—especially when the carrier is female. A small proportion of individuals who carry the premutation may themselves be at risk for early menopause or a related condition called FXTAS later in life.

    3. The protein

    One function of the FMRP protein in the brain is to put the brakes on another protein in the brain, called MGluR5. MGluR5 tells the neurons (brain cells) to grow dendrites, which are long, narrow parts that allow them to attach to other neurons. When the dendrites are the right size and shape, FMRP makes MGluR5 tell the neurons to stop. When FMRP is missing, the dendrites grow wild and uncontrolled.

    The brain uses the dendrites to send signals from one cell to another. When the dendrite is the right shape and size, it’s easy for the signal to get from one cell to another, like a car getting from Exit 1 to Exit 2 on the highway. But when the dendrites are out of control, it’s as if the highway between the two exits has sprouted many other exits and detours, and it’s a lot easier to get lost.

    This is what happens in your child’s brain—signals get lost on their way from one cell to another. This makes it hard to learn, and hard to respond to stimuli in the same way as people whose neurons can communicate easily.

    Symptoms

    Both boys and girls with fragile X may have certain physical, behavioral and intellectual traits. Remember that not everyone with the syndrome will have the same characteristics to the same degree.

    Physical characteristics

    Males with fragile X may have:

    • prominent ears
    • a long and narrow face
    • flat feet
    • large testicles (macroorchidism)
    • very flexible finger joints

    Females with fragile X may show similar physical characteristics, though this is less common. When the characteristics are present, they are often less distinctive.

    Intellectual and behavioral characteristics

    Males with fragile X may show:

    • delayed speech
    • delayed motor skills
    • repetitive and unclear speech
    • hyperactivity and short attention spans
    • autistic-like features, including poor eye contact, hand biting, hand flapping and hypersensitivity to environment (such as noise and crowds)

    Females may also show the above symptoms and/or distinct characteristics, including:

    • learning difficulties
    • short attention span
    • shyness
    • social anxiety

    Many of the problems, particularly the emotional ones, lessen as children get older.

    Symptoms of fragile X in childhood may appear to look like other disorders, such as autism, Prader-Willi syndrome and developmental delays. Always see a doctor for an exact diagnosis.

    FAQ

    Q: What is fragile X syndrome?

    A: Fragile X syndrome is a genetic condition that can result in varying levels of cognitive impairment, ranging from a normal IQ with mild learning disabilities to severe intellectual disability with or without autism. Sometimes children with fragile X syndrome have behavioral and emotional problems, such as hyperactivity, social anxiety and mood disorders. The symptoms tend to be more severe in boys than in girls.

    Q: Is there a cure for fragile X syndrome?

    A: Currently, researchers have yet to find a cure for fragile X syndrome. Until they do, there are many therapies available to help your child. While the details of his treatment plan will be tailored to his specific needs, common components include:

    • special education
    • speech and language therapy
    • occupational therapy
    • medication

    Q: What’s the long-term outlook for my child?

    A: Unfortunately, there’s no simple answer to this question, which depends on many factors. If your child is only mildly affected, he could do well for many years. Researchers at Children's and elsewhere are working to gain a better understanding of the condition and develop new drugs and treatment protocols. Read more about our research.

    Q: What will my child be able to do when he grows up?

    A: It’s hard to say, since there’s a lot of variability in the condition, and no two children with fragile X are the same. While many children will need ongoing support, some are able to be independent as adults, and researchers across the country are working on new treatments to make this possible for more and more children.

    Q: Will my child be able to go to school?

    A: Yes. He may need to go to a special school, and will probably need additional support, but he will be able to go to school. Although many children with fragile X syndrome experience some cognitive difficulties, all of them are capable of learning at their own pace. Finding learning techniques that work for your child can help him achieve these skills.

    Q: Do the symptoms of fragile X get worse with time?

    A: Fragile X is not progressive. But as children with fragile X get older, it can feel more difficult, because as children mature, more is expected of them, and it’s hard for them to keep up with their peers. There are lots of therapies available to help your child increase his ability to cope with this.

    Q: Will my child be able to have children?

    A: Yes. Women and men with fragile X syndrome are fertile. Girls with fragile X are at risk for having children who also have the syndrome. Boys are what’s called “premutation carriers,” even though they themselves have the full mutation. This means that:

    • all of their daughters will also be premutation carriers
    • their sons will neither have fragile X syndrome nor carry the mutation

    Q: Did I do anything to cause my child’s fragile X syndrome?

    A: No. There is nothing you did before or during pregnancy, or after your child was born, that could have caused your child to have fragile X syndrome. Fragile X is caused by a change in a gene that makes it not work properly. This is what leads to the problems seen in fragile X syndrome.

    Q: Could I have another child with Fragile X?

    A: Since the syndrome is genetic, you are at risk for having another child with fragile X. It’s important to know that you have no control over whether the fragile X gene gets passed on to your child or not. However, it is important to be tested to help determine what the risk of having another child with fragile X is. In addition, prenatal testing options are available, and genetic counseling before another pregnancy is strongly recommended to help you understand your personal risk and options.

    Q: Are other members of my family at risk for having a child with fragile X?

    A: Yes. Because fragile X is genetic, it may be unknowingly carried by other members of your extended family including your other children, so it’s important to inform them of your child’s diagnosis.

    Q: My child suffers from seizures. Is this common in fragile X syndrome?

    A: About 20 percent of people with fragile X experience seizures. Seizures usually begin early in childhood, and respond well to medication. They tend to disappear by the time your child is a teenager, but sometimes continue into adulthood.

    If you believe your child is having seizures, you should see a neurologist 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.

    Questions to ask your doctor

    After your child is diagnosed with fragile X syndrome, you may feel overwhelmed with information. It can be easy to lose track of the questions that occur to you.

    Lots of parents find it helpful to jot down questions as they arise—that way, when you talk to your child’s doctors, you can be sure that all of your concerns are addressed.

    Some questions you might ask include:

    • What should I be doing now?
    • Which care providers should my child see, and how often?
    • Who can I call if there’s a problem?
    • How can I explain this to my friends, family and doctors?

    Also, always ask questions about unfamiliar words—feel free to interrupt your child’s doctor to ask what something means, or at any time when you don’t understand something.

    Family planning

    Could I have another child with fragile X?

    Yes, you could. Let’s start by talking about what it means to be a “premutation carrier.”

    Fragile X is caused by a gene with an overly-large number of repeats in the DNA. Sometimes the gene will have more repeats than normal, but not enough to cause fragile X. When this happens, the person is said to be a premutation carrier. About 1 in 250 women are permutation carriers, and 1 in 700 men.

    While the premutation carrier does not have fragile X, the premutation gene is unstable, and can cause fragile X in future generations. For reasons that are not well understood, this happens only when the premutation is inherited from the mother.

    Could my brothers and sisters have children with fragile X?

    The answer is slightly different for mothers and fathers of children with fragile X:

    Mothers

    Because the mother inherited the premutation from one of her parents, a sibling or cousin may have also inherited it and be at risk for having children with fragile X syndrome. Testing the mother’s parents to determine from whom she inherited the premutation can tell us which side of the family is at risk.

    Fathers

    For fathers, it’s less likely that his siblings and cousins are at risk for having children with fragile X. This is because the father of a child with fragile X can either have the normal gene, or be a premutation carrier. This is done with a DNA test, though it’s usually not done unless the family has a history of fragile X. If the DNA test shows that the father is a premutation carrier, his siblings and cousins may also be premutation carriers, and be at risk of having children with fragile X.

    Are there any risks associated with being a premutation carrier?

    Unlike many genetic disorders, being a carrier does put you at an increased risk for certain medical problems:

    1. Female premutation carriers are at risk for premature menopause (before the age of 40).

    • This is seen in about 20 percent of premutation carriers.
    • Even when menopause occurs after age 40, it may begin six to eight years earlier in premutation carriers.

    If you are a premature carrier, talk with your primary care physician and OB/GYN if you are concerned about premature menopause, especially if you are planning on having more children. Rarely, females may be affected by FXTAS (see below).

    2. Male premutation carriers are at risk for a condition known as fragile X-associated tremor/ataxia syndrome (FXTAS).

    • FXTAS is characterized by progressively severe tremor and difficulty with walking and balance. It can also be associated with dementia and other neurological findings.
    • This condition appears to affect mostly older male premutation carriers, with signs appearing in their 50s to 60s.

    Recent research has shown that some premutation carrier females may also develop FXTAS, but not as often as premutation carrier males.

    Is there any way to tell whether I will have another child with fragile X syndrome?

    Prenatal diagnosis of the fragile X gene is available, although even with diagnosis, it is not possible to know what difficulties he or she may have. Talk to your genetic counselor for more information.

    Additional options that may be available include:

    • in vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD)
    • IVF with egg donor
    • adoption

    Of course, the decision to follow through with one of these options is a personal one, and what may be right for one couple is not right for another. It may help you to discuss these options with your doctor or genetic counselor.

    Fragile X and teens

    Puberty can be a tumultuous time for all children, and boys and girls with fragile X syndrome are no different. Some things to keep in mind:

    • Between 80 and 90 percent of males with fragile X have macroorchidism (large testicles). This generally does not cause any complications; but coupled with connective tissue problems, it may make them more likely to have certain kinds of hernias.
    • It’s important to address your daughter's emotional status before and during her period, as girls with fragile X are prone to mood swings and anxiety, particularly during times of hormonal changes.
    • Some girls may show signs of precocious puberty. If your daughter begins to show signs of puberty before she is 8 years old, she should be seen by an endocrinologist.
    • Sex education should be discussed in a developmentally appropriate manner with the assistance of the school, your pediatrician and/or the Fragile X Program.
  • The first step in treating your child is forming an accurate diagnosis. Fragile X may be challenging to diagnose, or may be diagnosed later in life, because many people—even doctors—aren’t familiar with it.

    Girls, in particular, may go undiagnosed because people still think they can’t have fragile X, and/or because their symptoms may be extremely mild.

    To diagnose your child, blood is taken and analyzed for the fragile X gene. Then we will meet with you and your family to discuss the results and outline the best treatment options.

    How do I know if my child should be tested for fragile X?

    The current recommendation is that any boy with intellectual delay should be tested for the fragile X gene. There isn’t a similar recommendation for girls, although specialists familiar with fragile X would likely test girls who show learning disabilities coupled with mood or behavior disorders, such as anxiety and attention-deficit hyperactivity disorder (ADHD).

    When are children diagnosed with fragile X?

    Boys with fragile X are usually diagnosed within the first three years of life. Problems often start to become obvious in second year, when they’re delayed in speech development and social interactions may start to go awry.

    Since girls have fewer symptoms, they tend to be diagnosed much later, often in their early teens. The diagnosis is usually made by a pediatrician, neurologist, geneticist, or developmental specialist.

    Can fragile X be diagnosed during pregnancy?

    The fragile X gene can be detected during pregnancy, but even if the test shows the full mutation, it’s impossible to know what any symptoms your child will have (or even if she or he will have any at all).

    Prenatal diagnosis can be done through:

    Chorionic villus sampling (CVS)

    • typically performed at 10 to 12 weeks gestation
    • a preliminary result is available in the first trimester, although confirmation may not be available until the second trimester
    • results from CVS analysis may be difficult to interpret; for further details, talk to your genetic counselor

    Amniocentesis (a test of the amniotic fluid)

    • typically performed at 15 to 18 weeks gestation
    • results are generally available in about 4 weeks

    Should I be tested for fragile X during my pregnancy?

    You should be tested if you know that you are a carrier of the fragile X gene or if there is a history of fragile X in your family. If you are not a carrier, but are concerned about fragile X, talk with your genetic counselor.

    What should I do after my child is diagnosed with fragile X?

    After your child is diagnosed with fragile X, contact a fragile X program. To talk to us at Children’s Hospital Boston, call our Fragile X Program at 617-355-4697, and we will arrange a time to meet with you and your child.

  • At Boston Children's Hospital, we know how devastating a diagnosis of fragile X can be, both for your child and for your whole family. That's why our physicians are focused on family-centered care: From your first visit, you'll work with a team of professionals who are committed to supporting all of your family's physical and psychosocial needs, including putting you in touch with other families with a child who has fragile X, and connecting you to community and educational services.

    When you call, we'll schedule a time for you and your child to come in for a comprehensive evaluation, so that our specialists can determine the best course of action for your child. Some of these specialists and the ways they can help include:

    Families new to the Fragile X Program at Children's are usually scheduled for six hours of evaluation over two days: one-and-a-half hours with the Genetics Program, one-and-a-half hours with the Developmental Medicine Center and three hours with the Occupational Therapy Service.

    Your family will meet with a geneticist and a genetic counselor who can answer any questions you have and provide information about fragile X, and if appropriate, we can connect you with other specialists, including:

    • neurologists
    • cardiologists
    • otolaryngologists
    • ophthalmologists
    • gastroenterologists
    • orthopedic surgeons

    We can also provide you with ideas on how to manage your child's environment. For example, limiting excessive sensory stimulation may prevent aggressive outbursts and social anxiety.

    Coping and support

    Shock, denial, fear, anxiety, guilt, sadness, grief and anger are all normal reactions when your child is diagnosed with a condition like fragile X. It's normal and acceptable to go through a range of emotions. Fortunately, there is a lot of help available to you.

    Other sources of support include:

    Parent to parent: Want to talk with someone whose child has been diagnosed with fragile X? We can often put you in touch with other families who have been through the same experience that you and your child are facing, and

    Support groups: We are in contact with all New England fragile X support groups. Support groups can be a great way to share experiences, get advice and remember that you're not in this alone.

    Faith-based support: If you and your family find yourself in need of spiritual support, we can connect you with the Children's chaplaincy. Our program includes nearly a dozen clergy representing Episcopal, Jewish, Lutheran, Muslim, Roman Catholic, Unitarian and United Church of Christ traditions who will listen to you, pray with you and help you observe your own faith practices during your treatment experience.

    Social work and mental health professionals: Our social workers and mental health clinicians have helped many other families in your situation. We can offer counseling and assistance with issues such as coping with your child's diagnosis, stresses relating to coping with illness and dealing with financial difficulties.

    On our For Patients and Families site, you can read all you need to know about:

    • getting to Children's
    • accommodations
    • navigating the hospital experience
    • resources that are available for your family

    Many parents of children with fragile X find FRAXA and the National Fragile X Foundation to be great resources.

    Tips on caring for the caregiver

    Caring for a child with fragile X syndrome can feel very stressful at times. It's important to remember that fragile X does not define your life or your family's life. Consider coping strategies such as:

    Taking care of other relationships: While you may feel like all your energy is focused on your child with fragile X, be sure to take care of your other family relationships. Communicate with each other but remember that people deal with emotions differently. Allow each other some leeway in how you communicate. Make sure your child's siblings understand his condition, and reassure them with your attention.

    Maintaining a sense of normalcy: Although your regular routine may become centered around your child with fragile X, try to keep your life as normal as possible. Continue doing activities that were important to you. Maintaining some sense of normalcy will help your family be in the best mindset to help your child.

    Keeping a journal: Keeping a journal of your child's health and medical care can be helpful for both you and your child's medical team, especially if you ever need to change specialists. You can also record your emotions and look back to reflect on how you have managed each phase of the situation.

    Researching and learning: Learn everything you can about your child's condition and the treatments available. Read inspirational stories about parents and children who have been through similar situations.

  • The Fragile X Program at Children’s Hospital Boston is committed to research aimed at understanding and treating fragile X.

    Program director Jonathan D. Picker, MD, PhD, is also the chairman of the Clinical and Professional Development Committee of the National X Fragile Clinical Research Consortium as well as a member of the steering committee charged with guiding the direction of national policy on care and research directions. As part of the consortium, our Fragile X Program works to coordinate research from across the nation and around the world, orchestrating projects that allow us to approach fragile X from complementary angles.

    Historically, fragile X has been a challenging topic for researchers, since its causes are located primarily in the brain. Among our current projects is a study on the effects of transcranial magnetic stimulation on fragile X. This is a non-invasive protocol aimed at:

    • providing confirmation that certain drugs really are helping people with fragile X

    • helping us understand exactly how fragile X affects learning and memory. With this knowledge, we hope to design more effective drugs or behavioral modification therapy.

    Children’s Intellectual and Developmental Disabilities Research Center (IDDRC) is one of 20 research centers around the country dedicated to the study of intellectual disability and developmental disabilities, with the goal of translating basic research into improved care approaches. Our scientists are conducting genetic, molecular, behavioral and biobehavioral researchon fragile X and other developmental disabilities.

    For more information, please see our Fragile X Program page.


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