Fragile X syndrome
We understand that you may feel overwhelmed and have a lot of questions when your child is diagnosed with fragile X, like:
- What is it?
- What should I do when my child is diagnosed?
- What are the treatments?
- What’s the long-term outlook for my child?
We’ve tried to provide some answers to those questions here, and when you meet with our experts, we can explain your child’s condition and options fully.
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:
- ear infections
- eye problems, such as strabismus (inability to focus both eyes on an object), hyperopia (far-sightedness) and astigmatism
- toilet training problems
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
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.
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.
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.
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
- 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.
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
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.
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:
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.
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
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.