Fragile X syndrome facts*

*Fragile X syndrome facts medically reviewed by Charles Patrick Davis, MD, PhD on 1/15/2015.

  • Fragile X syndrome (also called Fragile X) is the most common inherited form of mental problems (mental retardation).
  • Fragile X syndrome is caused by changes in a single X chromosome (FMR1).
  • FMR1 does not produce enough protein (FMRP) that works cell communication.
  • Normal X genes that control FMR1 levels have promoter regions consisting of about 6 to 40 CGG; Fragile X genes have about 55 to 200 (termed premutation) or more than about 200 regions (termed full mutation).
  • About 100 trillion cells make up a human body and each should have 46 chromosomes, but males have only one X chromosome; so, if it contains a FMR1 chromosome, the effect of the lack of FMRP is more significant than in females.
  • Approximately one in 3,600 to 4,000 males is affected by the full mutation of the FMR1 gene, and about one in 468 males has the premutation form of the FMR1 gene; about one in 151 females in the general population has the premutation while about one in 4,000 to 6,000 females is affected by the full mutation (these are estimates only).
  • The Fragile X gene is only carried on an X chromosome; both males and females may transmit a Fragile X (FMR1) gene on their X chromosome so either a man or a woman may be a carrier.
  • The signs and symptoms of Fragile X syndrome have five general categories where individuals often show altered or arrested development.
    1. Intelligence and learning (low IQs)
    2. Physical (long face or jaw, short stature, enlarged testicles)
    3. Social and emotional (anxiety)
    4. Speech and language (stuttering and disorganized speech)
    5. Sensory (sensitive to certain stimuli like sounds, balance problems)
  • Each individual may exhibit variations in the above five categories.
    • Features of autism and fragile X overlap, but the core deficit in autism is social interaction while the core deficit in fragile X is intellectual function and hyper arousal/anxiety.
    • Angelman syndrome is a genetic disorder that also has features of fragile X with delayed development and severe speech impairment along with seizures, small head size, and hand-flapping movements; but is due to genetic defects or alterations in a gene termed UBE3A.
    • Myotonic dystrophy (muscular degeneration and tissue loss) related to fragile X syndrome as both have similar genetic alterations (repeat expansions of genetic coding)
  • Currently, there is no cure for Fragile X syndrome nor are there any definitive treatments other than helping the individual develop to their maximal potential through education; therapies such as speech, language, behavioral, and physical; and other therapies. Fragile X detects FMR1 DNA (PCR or Southern blot methods)
  • Medication therapy may only help certain individuals with certain severe problems and should be prescribed only by the patients' doctors; there is no medication that can cure Fragile X syndrome.
  • Adults with Fragile X syndrome may benefit from a team approach to help the patient adjust to independent living, if possible.
  • IIf a family member has been diagnosed with Fragile X syndrome, other family members may want to be tested to determine if they carry a Fragile X chromosome; there are several accurate DNA tests available for gene testing (see above) and for determining the amount of FMRP produced. Prenatal tests are also available.
  • Research is ongoing; gene therapy, gene activation, and FMRP replacement therapy are several areas that may lead to treatments, or possible cure or prevention, in the future.
  • Several national organizations may provide additional information on Fragile X syndrome (for example, American Association on Mental Retardation and the National Institute of Child Health and Human Development).
A diagnosis of fragile-X associated tremor/ataxia syndrome did not come easy for Marcia and Henry.

Two Newlyweds Fight Fragile-X Associated Tremor/Ataxia Syndrome (FXTAS)

One caregiver's story

My name is Marcia*, but sometimes I call myself the "bride of FXTAS." FXTAS stands for Fragile-X Associated Tremor/Ataxia Syndrome, the degenerative neurological disorder that attacked my 64-year-old husband Henry* a month after we were married in 1999. The first noticeable symptom was that Henry fell down while playing golf - medics were called and could find nothing apparently wrong with Henry. It took over five years of worsening symptoms - including more frequent falls, difficulty walking, cognitive decline and incontinence—examinations by five neurologists and many diagnostic tests before Henry was diagnosed with FXTAS. For the seven-plus years of our marriage....

*Names have been changed to maintain privacy.

What is Fragile X syndrome?

Fragile X syndrome (also called Fragile X) is the most common inherited form of mental retardation.* It results from a change, or mutation, in a single gene, which can be passed from one generation to the next. Fragile X appears in families of every ethnic group and income level.

Symptoms of Fragile X syndrome occur because the mutated gene cannot produce enough of a protein that is needed by the body's cells, especially cells in the brain, to develop and function normally. The amount and usability of this protein, in part, determine how severe the effects of Fragile X are.

The most noticeable and consistent effect of Fragile X is on intelligence. More than 80 percent of males with Fragile X have an IQ (intelligence quotient) of 75 or less.1 The effect of Fragile X on intelligence is more variable in females. Some females have mental impairment, some have learning disabilities, and some have a normal IQ.

People with Fragile X syndrome also share certain medical problems as well as many common physical characteristics,2 such as large ears and a long face. In addition, having Fragile X is often associated with problems with sensation, emotion, and behavior.

The National Institute of Child Health and Human Development (NICHD), part of the National Institutes of Health (NIH), is a major sponsor of research on Fragile X syndrome. Since 1991, when researchers funded by the NICHD discovered the gene that causes Fragile X, scientists have learned a great deal about that gene's structure and functions. The NICHD continues to support clinicians and scientists around the world who are working to find effective behavioral or other therapies, medical treatments, and prevention strategies for Fragile X.

* The NICHD recognizes that there is a debate about the use of the term "mental retardation," and that self-advocacy groups and professional associations are currently discussing alternative terms. Until a consensus is reached, and with the goal of addressing health-related issues faced by people with what has been traditionally known as "mental retardation," this article uses that term to describe some features related to Fragile X syndrome. For more information, please see the Additional Resources section of this article.

What causes Fragile X syndrome?

The underlying cause of Fragile X is a change in a single gene, the Fragile X Mental Retardation 1 (FMR1) gene, which is found on the X chromosome. (See the Human cells 101 section for more information about the X chromosome.) But how does this change cause Fragile X?

Causes of Mental Retardation

Mental retardation is associated with more than 500 conditions. Some of the most commonly known genetic causes among these are:

  • Down syndrome, due to an error in the number of chromosomes
  • Fragile X, due to a repeat in the genetic code that leads to a lack of production of a certain protein
  • PKU (phenylketonuria), due to an error in a single gene that makes a defective enzyme

Other causes of mental retardation that can occur during pregnancy include the mother's excessive use of alcohol, exposure to poisons in the environment, and diseases such as rubella.

Genes contain the information used by other parts of a cell to make proteins. Proteins are the body's building blocks. Each protein performs a specific job. They make up the structure of your organs and tissues and are needed for all of your body's chemical functions.

Each gene contains information for making at least one protein. If this information is changed, then the cell may not be able to make that protein, or it may not be able to make a form of the protein that the body can use. Fragile X occurs because the FMR1 gene is unable to make normal amounts of usable Fragile X Mental Retardation Protein, or FMRP.

The amount of FMRP in the body is one factor that determines how severe the effects of having Fragile X are. A person with nearly normal levels of FMRP usually has mild or no symptoms, while a person with very little or no normal FMRP has more severe symptoms.

Scientists are still studying the role of FMRP in the body. One current research study revealed that certain cell processes brain cells use to communicate with one another occur in excess in mice that have little or no FMRP; that is, he brain cells may communicate too much or may communicate inappropriately. Researchers believe that FMRP may regulate the amount of communication between cells and keep it under control. Scientists are hopeful that they can identify a similar function for FMRP in humans.

What keeps the FMR1 gene from producing FMRP in Fragile X syndrome?

The information for making a protein has two parts: the introduction, and the instructions for the protein itself. Scientists call the introduction "the promoter region" of the gene because of its role in starting the protein-building process. (For a more complete description of how proteins are made and the parts of a cell involved in making a protein, see the Human cells 101 section.)

The promoter region of the FMR1 gene contains repeats of a specific sequence (cytosine-guanine-guanine or CGG-see the Human cells 101 section for specific information about the CGG sequence) that, when normal, controls the activity level of the gene in building FMRP.

The number of repeated sequences in the promoter region varies from person to person. Most people who do not have Fragile X have between six and 40 CGG repeats,3 with the average being about 30 repeats in the promoter region.4

However, in a mutated FMR1 gene, the promoter may have hundreds of repeated sequences.

  • A gene with 55 to 200 repeats is generally considered a "premutation."
  • A gene with more than about 200 repeats is called a "full mutation."

The larger number of repeats (more than 200) inactivates the gene. This inactivation process is called methylation. When the gene is inactivated, the cell may make little or none of the needed FMRP.

What goes wrong in a mutated gene?

A number of things can go wrong in a gene that can result in a mutation. The mutation affects the gene's ability to make the needed amount of protein or to make enough usable protein. Some of these mutations include:

Part or all of a gene may be missing.
Chemical sequence of the instructions for making a protein is incorrect.
The promoter region is too big.

In the case of Fragile X, usually the FMR1 gene is present, and its chemical sequence is correct, so neither A nor B apply. However, a mutated FMR1 gene includes repeats of a specific sequence in its promoter region, which creates a mutation like the one shown in situation C.

The number of repeats and their effects are still being studied. At the time this article was printed, the numbers included here were the most commonly cited for premutation in the published scientific literature: Fragile X Syndrome Handbook (2002) National Fragile X Foundation; American College of Medical Genetics Statement: Technical Standards and Guidelines for Fragile X (2001); Rousseau et al. (1996) American Journal of Human Genetics 59(Suppl):A188-1069. However, some research categorizes the premutation differently. For instance, in Crawford et al., 61 to 200 repeats is a premutation, while 41 to 60 repeats is an intermediate mutation (Genetics in Medicine 2001; 3:359-371). The American Academy of Pediatrics Policy Statement. Health Supervision for Children with Fragile X Syndrome uses 50 to 200 repeats for premutation (Pediatrics 1996; 98(2): 297-300). Tassone et al. (American Journal of Medical Genetics 2000; 97[3]:195-203) use large premutation (100 to 200 repeats) and small premutation (55 to 100 repeats). You may encounter differences in the number of repeats for a premutation depending on your source.

One interesting aspect of Fragile X is that, even with a full mutation gene, the body may be able to make some FMRP. Three things affect how much FMRP is produced:

  • The number of CGG repeats. People with a full mutation (200 or more repeats) usually have many of the more severe symptoms associated with Fragile X. In contrast, people with a premutation gene may have few, if any, symptoms and may not even know they carry a mutated gene. Researchers are still trying to sort out any, patterns or trends in the symptoms of people with a premutation gene.
  • Being mosaic. Not every cell in the body is exactly the same. In Fragile X, this means that some cells may have 200 or more repeats in the FMR1 promoter, while other cells, premutation cells, may have fewer than 200 repeats. This is called being "mosaic," meaning either that the mutation is in some of the cells, but not all of them, or that it is not in all of the cells to the same degree. The premutation cells may be able to make FMRP. Similarly, methylation may not happen at all, or to the same degree, in every cell. If enough cells produce FMRP, the symptoms of Fragile X will be milder than if none of the cells produce FMRP.
  • Being female. Because females have two X chromosomes, females with Fragile X have one normal FMR1 gene and one mutated FMR1 gene in most of their cells. But, only one X chromosome is active in each cell, and only the genes on the active chromosome are used to build proteins. The cell seems to randomly choose which chromosome is used. In some cells, then, the X chromosome that contains the normal FMR1 gene is active, and the cell uses it to make FMRP. As a result, even females with a full mutation are often able to make some of the needed protein. For this reason, the symptoms of Fragile X usually affect females less often and less seriously than males.

Human cells 101

More than 100 trillion cells make up the human body. Most of these cells contain all the genes and other information needed to "build" a human being. Much of this genetic information is found in the nucleus of the cell, a "control center" that keeps all the material together in one place.

Illustration of how DNA is made.

The nucleus stores its genetic material in packages called chromosomes. Most people have 46 chromosomes in each cell-23 from their mother and 23 from their father. After fertilization, the two sets of chromosomes match up to form 23 pairs. The chromosomes in the 23rd pair are called the sex chromosomes, X and Y; they determine a person's sex. Males usually have one Y chromosome and one X chromosome; females usually have two X chromosomes.

Each chromosome is made up of genes. Genes contain the information used by other parts of the cell to make proteins, the body's building blocks. Proteins make up the structure of your organs and tissues; they are also needed for your body's chemical functions. Each protein performs a specific job in different types of cells, and the information for making at least one protein is contained in a single gene.

Genes are made up of various lengths of DNA, which contains four chemicals: adenine (A), guanine (G), cytosine (C), and thymine (T). These chemicals line up like beads on a necklace to form strands of code. They also pair up with each other to form the double strands that are characteristic of DNA.

The gene's chemical code for a protein has two parts: the introduction area (promoter), and the instructions for creating the protein. The instructions for making the protein are inside the cell's nucleus, but the parts that actually make the protein are outside the nucleus. To send the instructions to the protein-producing areas of the cell, the gene "reads" the chemical code and rewrites it into a new form (called messenger RNA). The new form is then sent out of the cell's nucleus to make proteins. But, if either the original code or the new form of the code is incorrect or has missing parts, the cell can't make the correct protein. Without the protein, the body may not develop or function normally.

This is what happens in Fragile X. The FMR1 gene contains too many repeats of one specific sequence, CGG, which is an important part of the promoter region for making FMRP (see the figure below).

Illustration of the promoter region on a <i>FMR1</i> mutated gene.
Illustration of the promoter region on a FMR1 mutated gene.

The number of CGG repeats affects how the code is read and rewritten into its new form. So when the new form of the code gets to the protein-making areas of the cell, the cell has trouble using it to make FMRP, the protein that is abnormal, missing, or in low amounts in people with Fragile X. The cell either can't use the code, and so makes no FMRP, or tries to use the code and makes abnormal or unusable FMRP.

How many people are affected by Fragile X syndrome?

Currently, researchers don't know exactly how many people have either the full mutation or the premutation form of the FMR1 gene. Even though researchers can estimate the number of people affected by Fragile X, these estimates can be very different.*

The important thing to remember is that, when you consider the individuals affected by full mutation and premutation forms of the FMR1 gene, their families, and their communities, this condition impacts hundreds of thousands of people.

 For more information, please consult the specific articles or the national organizations listed in the Where can I go for more information about Fragile X syndrome? section of this article.

How is Fragile X syndrome inherited?

The gene for Fragile X is carried on the X chromosome. Because both males (XY) and females (XX) have at least one X chromosome, both can pass on the mutated gene to their children

Diagram A
Father
Y XFragile
Mother
X Boy

XY

Girl

XXFragile

X Boy

XY

Girl

XXFragile

A father with the altered gene for Fragile X on his X chromosome will only pass that gene on to his daughters. He passes a Y chromosome on to his sons, which doesn't transmit the condition. Therefore, if the father has the altered gene on his X chromosome, but the mother's X chromosomes are normal, all of the couple's daughters would have the altered gene for Fragile X, while none of their sons would have the mutated gene (see Diagram A).

Current research indicates that a father can pass on the premutation form of the FMR1 gene only to his daughters. In other words, if a daughter inherits the mutated FMR1 gene from her father, she will get only the premutation from him, not the full mutation. Even if the father himself has a full mutation, it appears that sperm can carry only the premutation. Scientists don't understand how or why fathers can only pass on the milder form of Fragile X to their daughters. This remains an area of focused research.

Because mothers pass on only X chromosomes to their children, if the mother has the altered gene for Fragile X, she can pass that gene to either her sons or her daughters. If the mother has the mutated gene on one X chromosome and has one normal X chromosome, and the father has no genetic mutations, all the children have a 50-50 chance of inheriting the mutated gene (see Diagram B).

Diagram B
Father
Y X
Mother
XFragile Boy

YXFragile

Girl

XXFragile

X Boy

XY

Girl

XX

The odds noted here apply to each child the parents have. Having one child who receives an X chromosome with the FMR1 mutation does not increase or decrease the chances of having another child with the mutated FMR1 gene. Nor do these odds influence the severity of the symptoms. Having one child with mild symptoms does not mean that the other children will have severe symptoms, and having a child with severe symptoms does not mean that other children will have mild symptoms.

A premutation gene is less stable than a full mutation. In some cases, the mutated gene may expand from the premutation to the full mutation as it is passed on from mother to child. The chances of expansion depend on the number of repeats in the promoter of the premutation gene; the higher the number of repeats, the more likely it is that the gene will expand. These chances also increase with each generation. Children of a mother who has the premutation, then, may have no genetic mutation, the premutation, or the full mutation.

Further, because an altered FMR1 gene can be passed on without symptoms, many people are unaware that they have it. As a result, a premutation form of the FMR1 gene can be silently passed through a family for generations, with no one ever showing any symptoms. However, with each generation, it becomes more likely that the premutation gene will expand its number of repeats to become a full mutation gene, which would also increase the number of and seriousness of symptoms.

What are the signs and symptoms of Fragile X syndrome?

Not everyone with Fragile X has the same signs and symptoms, or to the same degree. Even affected children in the same family can have different signs and symptoms. These differences often make Fragile X hard to diagnose. However, because everyone with Fragile X has too little FMRP, they do share a pattern of certain physical, social, mental, and sensory characteristics. Although most of the Fragile X research to date has focused on children, adults with Fragile X also have most of these signs and symptoms.

In general, the signs and symptoms of Fragile X fall into five categories:

  • Intelligence and learning
  • Physical
  • Social and emotional
  • Speech and language
  • Sensory
  • Disorders commonly associated or sharing features with Fragile X

Now consider each category in more detail.

Intelligence and learning

Many people with Fragile X have impaired intellectual functioning, which affects their ability to think, reason, and learn. In most cases, researchers use an intelligence test to measure intellectual functioning, resulting in an IQ (intelligence quotient) score. But this score reflects many things besides the ability to think. Attention disorders, hyperactivity, anxiety, and language processing problems can interfere with test-taking skills and learning. Because many people with Fragile X have these problems, a person with Fragile X may have more capabilities than his or her IQ score suggests.

Researchers consider people who score between 85 and 115 on an IQ test to have "average" intelligence.7 On the whole, less than 20 percent of males with Fragile X have an IQ in this range.2 At the same time, few people with Fragile X are severely or profoundly impaired, with IQs below 40 or 25, respectively.8 In general, those with a full mutation tend to have an IQ somewhere in between 40 and 85, which is considered mild to moderate mental impairment.

Suggestions for working with individuals with Fragile X

  • Know the learning style of the individual.
  • Develop a consistent daily schedule or routine.
  • Use visual signs (pictures, sign language, logos, words) and concrete examples or materials to present ideas, concepts, steps, etc.
  • Prepare the individual for any changes in routine by explaining them ahead of time, possibly using visual signs.
  • Include functional goals with academic goals; for instance, teaching the individual the names of different pieces of clothing as well as how to dress him/herself.
  • Provide opportunities for the child to be active and move around.
  • Use computers and interactive educational software.
  • Provide a quiet place where the child can retreat and regroup.

Females tend to be less seriously affected by Fragile X than males. Even among females who have full-mutation FMR1 genes, only about one-third have an IQ in the mental retardation range.6 Females with Fragile X are more likely to have relatively normal cognitive development, or they may show a learning disability where their academic achievement in some areas is lower than their overall ability to learn. For example, a female with a learning disability in math might score several grades below her grade level in math, even though her IQ is within the normal range.

Many factors influence intelligence, and, like most individuals, people with Fragile X have areas of both strength and weakness. For example, people with Fragile X tend to have good memories for pictures and visual patterns. This ability helps them to learn to recognize letters and words. They are also generally able to follow instructions that are presented as pictures. Their main weaknesses are in thinking about abstract ideas, organizing information, planning ahead, and solving problems.

No matter what their IQ or areas of intelligence, all children and adults with Fragile X are capable of learning. Most children will progress in school and develop basic academic skills. Many adults can learn to take care of themselves and work at a job. People with Fragile X may need more time to learn, special teaching methods, or a specially tailored environment (see the Suggestions for working with individuals with Fragile X box), but they usually can and do make steady progress.

Physical

Many infants and young children with Fragile X have no distinctive physical features. Some children have very soft, velvety skin, a broad forehead, or a slightly larger head than other children their age.

However, when these children enter puberty, usually around age 11, they may begin to develop certain features that are typical of teens and adults with Fragile X, such as a longer face or jaw and larger, more noticeable ears. Most do not grow as tall as their peers, or as tall as one might expect them to grow, based on the height of their family members.

Other physical changes also come with puberty for those who have Fragile X. Many males develop enlarged testicles, a condition called macro-orchidism (pronounced mack-roe-ORK-id-izm). With this condition, the testicles may grow to twice their normal size. This condition is not due to hormonal imbalance and does not affect sexual development.

One job of FMRP may be to help the body maintain its connective tissues. Connective tissues support the body, inside and out. Many people with Fragile X have loose, flexible joints. They may have flat feet and be able to extend joints like the thumb, knee, and elbow further than normal. Weak connective tissue can predispose a person to certain medical conditions, such as hernia and frequent middle ear infections. Weak connective tissue can also affect the valves and vessels of the heart, so that blood in the heart may not flow smoothly, which creates a heart murmur (called mitral valve prolapse, pronounced my-trell valv proh lapss). Although it involves the heart, this condition is usually not life threatening, but it is a good idea for a person with a heart murmur to be monitored by a health care professional on a regular basis.

Late in life, some males who have a premutation may develop hand tremors10 and problems with walking.

How does Fragile X affect the brain?

Understanding how Fragile X affects the brain and learning what role FMRP plays in normal brain development and function are areas of active research. For instance, some evidence suggests that FMRP is involved in forming pathways in the brain.

Normally, brain cells called neurons have special areas that grow toward each other to form connections. These connections, called "synapses," are arranged in neural pathways. Thoughts, sounds, and memories are recorded and stored in these pathways. However, not every experience recorded in these neural pathways is useful or needs to be kept throughout life. So, as part of normal development, the brain "prunes" itself. Like pruning the branches of a tree, removing unneeded or ineffective pathways in the brain strengthens other pathways and makes room for new growth and new learning.

FMRP may somehow influence the pruning process in the brain. People without enough FMRP may have may have too many neural pathways or many connections that don't work well. This situation would explain some of the symptoms of Fragile X, such as an extreme sensitivity to new sights, sounds, smells, and touches.

Using mice and fruit flies that no longer have a working gene to make FMRP, scientists are working to understand how the absence of this protein affects the brain. Recent research is trying to determine whether a certain process that runs out of control in mice with little or no FMRP leads to the behavioral and learning problems typical in people with Fragile X. Such animal studies may reveal exactly how FMRP functions in the brain and suggest ways to correct situations caused by a lack of the protein.

Fragile X affects females in some different ways. About 16 percent11 to 19 percent12 of females who have a premutation gene experience premature ovarian failure (POF), meaning their ovarian function stops before normal menopause, sometimes well before the age of 40. Some may experience POF as early as their mid-twenties. POF affects a woman's ability to get pregnant. It is important, then, for women to know whether or not they have a premutation gene, and to have this knowledge early enough, so that they can consider their options for having a family. In contrast, POF occurs in only 1 percent of women who have two normal FMR1 genes,13 and the average age of menopause for women who are not affected by Fragile X is 51. Women who have a full mutation gene do not lose ovarian function as early as women with a premutation gene, but they still tend to begin menopause earlier than women who are not affected by Fragile X. Scientists do not know why the effect is milder in women who have a full mutation form of the gene than in women with a premutation form of the gene.

Social and emotional

Most children with Fragile X-especially boys-feel a great deal of social anxiety; that is, they aren't completely comfortable in new situations, meeting new people, or doing new things. Their level of anxiety can be so high that they may avoid social situations. When these children do seek contact with others, they are often extremely nervous or uncomfortable. Their anxiety may show up as a lack of eye contact and/or fast, choppy speech. Although all children feel some degree of social anxiety, this discomfort usually doesn't keep them from being social, as it may for children with Fragile X.

In addition to being anxious, males with Fragile X tend to be easily upset. They are easily overwhelmed with sights and sounds (see the What are the signs and symptoms of Fragile X?-Sensory section of this article for more information), and can become very distressed in a busy store or restaurant. Unexpected changes in routine, like entering a new class or classroom, can also upset them. Some children respond by becoming extremely rigid or tense, while others whine or cry. At times, their reactions can spill over into tantrums or repetitive actions, such as rocking back and forth and biting themselves. In adolescence, changes, such as rising hormone levels, may make these outbursts more extreme. In one study of teenage males with Fragile X, about one-third showed angry, aggressive behavior.8 Such behavior can get them into trouble at school. Providing medication and a calm environment can help keep such behaviors from getting worse. (See the Are there treatments for Fragile X? section for more information.)

In addition, males with Fragile X tend to experience much longer periods of anxiety than their peers. Like other males, their heart rate and other signs of nervousness increase when they do challenging tasks, but many males with Fragile X stay highly anxious for much longer time frame. So, in addition to having a level of anxiety that is often higher than their peers, males with Fragile X also take longer to calm down than other males do.

Females with Fragile X may have social problems, too, but theirs tend to be milder. A female with Fragile X may feel uneasy around strangers or have trouble making friends, but these females don't tend to be aggressive as adolescents.

Speech and language

Language difficulties in children who have Fragile X range from mild stuttering to more severe problems with basic language skills. Basic language skills include the ability to pronounce words clearly, to speak and write using words and grammar correctly, and to communicate in meaningful ways.

Females with Fragile X rarely have severe problems with speech or language. In fact, many have vocabulary and grammar skills that are appropriate for their age, which can help them learn to read and write. However, their social anxiety and shyness may get in the way of communication. Some females with Fragile X speak in a rambling, disorganized way or often get off the subject. Most males with Fragile X have more serious problems expressing themselves. These difficulties typically include problems speaking clearly and other problems with language that can be moderate to severe. In terms of speech, males with Fragile X often have problems coordinating the structures, vocal processes (such as pitch, loudness, and tone), and movements needed for clear speech. They often have difficulty receiving and processing spoken information, such as following spoken directions, storing words and concepts for future use, and creating their own meaningful responses to questions or comments.

Males with Fragile X may stutter or leave sounds out of their words. Many repeat themselves, restart the same sentence many times, or ask the same question again and again. Some may talk too fast, mumble, or speak in a loud, high voice. Some of these difficulties may be due to sensory overload or social anxiety, rather than a problem with the parts of the brain that control speech and language.

Perhaps most importantly, males with Fragile X usually have difficulty using speech and language in social contexts. They often seem unaware of conversational "clues," such as facial expressions, tone of voice, and body language. As a result, they may speak out of turn, fail to answer a question, or turn away because they aren't sure what to do. Unlike males with other developmental disorders, like autism, males with Fragile X seem to be very interested in communicating, but may experience sensory overload or social overload when they try to hold a conversation.

For some children, language problems are more severe. Many children with Fragile X begin talking later than expected. Most begin using words around age four, but some may not talk until age of six or eight.6 Most talk eventually, but some may remain nonverbal throughout life. For these nonverbal children, a wide variety of picture-based and computer-based devices may help them to communicate, which could also reduce behavior difficulties that result from not being able to talk. Pictures, sign language, and generic gestures can also be helpful for all children with Fragile X, before they start talking.

Sensory

Many children with Fragile X are sensitive to certain sensations.

Disorders commonly associated or sharing features with Fragile X

Autism. Most males and about one-third of females with Fragile X show some autism-like behaviors, such as flapping hands, biting themselves, repetitious actions, and walking on toes.14 About 33% of children with Fragile X show enough of these behaviors to receive a formal diagnosis of autism.15 However, among people diagnosed with autism first, only about 4 percent are found to have an X chromosome with the FMR1 gene mutation.

Attention Deficit Disorder (ADD)/Attention Deficit Hyperactivity Disorder (ADHD). Between 80 and 90 percent of males, and 35 to 47 percent of females with Fragile X have an attention disorder.16,17 They are unable to focus their attention and stay with a task. They may be disorganized. Some are hyperactive and seem to be constantly in motion.

Connective Tissue Problems. Due to weak connective tissue, people with Fragile X have a higher risk of dislocating their joints and developing hernias and ear infections than those who aren't affected by Fragile X. About half of adults with Fragile X have a heart murmur caused by mitral valve prolapse,17 which is usually not life threatening.

Seizures. About 20%6 of children with Fragile X also experience seizures. In most cases, seizures are successfully treated with medication and disappear by adolescence.

Premature Ovarian Failure (POF). POF occurs when a woman's ovaries stop working properly and she is under the age of 40. As mentioned earlier in this article, about 16 to 19 percent of females who carry a premutation gene for Fragile X experience POF, some as early as age 20.10,11 Women with a full mutation gene for Fragile X are less likely to have POF, but do tend to go through menopause earlier than women who do not carry a mutated gene.

They may become frantic at the sound of a loud noise or may be easily distracted by slight sounds in the room. They may be bothered by the texture of their clothes against their skin, or they may be unable to focus on the parts of their environment that are important, such as the sound of the teacher's voice. Infants with Fragile X may have problems drinking from a bottle, perhaps because the feel of the nipple upsets them. Some children try to avoid being touched, and even a brief tickle or hug may be overwhelming. Even though many of these symptoms are often life-long, most people affected by Fragile X, with the proper intervention, can find ways to handle or avoid the discomfort. (See the Are there treatments for Fragile X syndrome? section for more information.)

Children with Fragile X may also have problems with balance. A sense of balance helps keep the body upright and stable. Problems with balance, coordination, and connective tissue can cause difficulties for children with Fragile X as they learn to sit, stand, and walk, or later, to ride a bike. Even so, most children with Fragile X learn to do these tasks.

Is there a cure for Fragile X syndrome?

Although research continues and knowledge about Fragile X and its characteristics grows, there is no cure for Fragile X at this time.

Are there treatments for Fragile X syndrome?

Currently there is no definitive, single treatment for Fragile X. However, there are a variety of ways to help minimize the symptoms of the condition. Children with Fragile X who receive appropriate education, behavioral or physical therapy, and medication have the best chance of using their individual capabilities and skills. Even those with significant mental retardation can learn to master many self-help skills.

One important factor in developing a child's long-term potential is early intervention. The sooner a child begins to get help, the more opportunity for learning. Because a young child's brain is still forming, early intervention gives children the best start possible and the best chance of developing their full potential. Even so, no matter when a person is diagnosed with Fragile X, it's never too late to benefit from treatment.

Some treatment options include:

  • Educational options
  • Therapeutic options
  • Medication options

Educational Options

Most children with Fragile X, including those with severe mental retardation, are guaranteed free, appropriate public education under federal law. Public Law 105-17: The Individuals with Disabilities Education Act-IDEA (1997) makes it possible for children with disabilities to get free educational services and educational devices to help them learn as much as they can. Each child is entitled to these services from age three through high school, or until age 21, whichever comes first. Also, every state operates an early intervention program for children from birth to age three; children with Fragile X should qualify for these services. The law also states that children must be taught in the least restrictive environment, appropriate for that individual child. This statement does not mean that each child will be placed in a regular classroom, but instead, that the best combination of one-to-one tutoring, small group work, and regular classroom work will be arranged.

Because not all children or adolescents with Fragile X have mental impairment or special needs, a medical diagnosis of Fragile X does not guarantee access to special education services. The child must have certain cognitive or learning deficits. Parents can contact a local school principal or special education coordinator to learn how to have their child examined to see if he or she qualifies for services under the IDEA.

If a child qualifies for special services, a team of people, including the child's parents or caregivers, teachers, school psychologist, and other child development specialists, will work together to design an Individualized Education Plan (IEP) for the child. The IEP includes specific learning goals for that child, based on his or her needs and capabilities. The team also decides how best to carry out the IEP, such as making choices about classroom placement for the child, determining any devices or special assistance the child needs, and identifying the developmental specialists who will work with the child.

A child with Fragile X should be evaluated and re-evaluated on a regular basis by his or her special services team. In this way, the team can determine how the child is doing and whether any changes are needed in his or her treatment (for instance, changes to the IEP, changes in classroom placement, or changes in other services) to ensure the child is getting the best possible care.

In general, there are three classroom placement options for a child with Fragile X, based on his or her specific abilities and needs:

  • Full inclusion in a regular classroom. The child spends the full day in the regular classroom rather than just among children with special needs. This situation is sometimes called "mainstreaming." Specialists work with the child in the classroom, with other students present. There may be an aide assigned to help the child with certain kinds of tasks.
  • Inclusion with "pull-out" services. In this type of placement, the child spends most of the day in the regular classroom. However, for part of the day, he or she attends small-group classes with one or more developmental specialists, such as a speech-language therapist or a physical therapist. This arrangement gives the child exposure to children who do not have special needs, as well as more individual attention to his or her areas of special needs
  • Full-time, special education classroom. Some children with Fragile X may do better in a smaller special education class than in a regular classroom. Special education classrooms usually have fewer children and offer more individualized attention from the teacher. Such programs may be offered at the school or in central locations that serve a larger area. Regional special education centers often have facilities and equipment designed for children with special needs. For some children, a special school for children with similar disabilities may be the best option.

Placement decisions should be based on each child's needs and abilities. In most cases, these decisions require a balance of various priorities to maximize the chances for the best possible outcome for the child.

Therapeutic Options

A variety of professionals can help individuals with Fragile X and their families deal with symptoms of the disorder. Such assistance is usually most effective when provided by health care professionals experienced with Fragile X.

  • Speech-language therapists can help people with Fragile X to improve their pronunciation of words and sentences, slow down speech, and use language more effectively. They may set up social or problem-solving situations to help a child practice using language in meaningful ways. For the minority of children who fail to develop functional speech, this type of specialist may work with other specialists to design and teach nonverbal ways of communication. For example, some children may prefer to use small picture cards arranged on a key ring to express themselves; or they may learn to use a hand-held computer that is programmed to "say" words and phrases when a single key is pressed.
  • Occupational therapists help find ways to adjust tasks and conditions to match a person's needs and abilities. For example, this type of therapist might teach parents to swaddle or massage their baby who has Fragile X to calm him or her. Or the therapist might find a specially designed computer mouse and keyboard or a pencil that is easier for a child with poor motor control to grip. At the high school level, an occupational therapist can help a teenager with Fragile X identify a job, career, or skill that matches his or her interests and individual capabilities.17
  • Physical therapists design activities and exercises to build motor control and to improve posture and balance. They can teach parents ways to exercise their baby's muscles. At school, a physical therapist may help a child who is easily over-stimulated or who avoids body contact to participate in sports and games with other children.
  • Behavioral therapists try to identify why a child acts in negative ways and then seek ways to prevent these distressing situations, and to teach the child to cope with the distress. This type of specialist also works with parents and teachers to find useful responses to desirable and undesirable behavior. During puberty, rising and changing hormone levels can cause adolescents to become more aggressive. A behavioral therapist can help a teenager recognize his or her intense emotions and teach healthy ways to calm down.

The services of these specialists may be available to pre-school and school-aged children, as well as to teens, through the local public school system. In a school setting, several specialists often work together to assess each child's particular strengths and weaknesses, and to plan a program that is specially tailored to meet the child's needs. These services are often free. More intense and individualized help is available through private clinics, but the family usually has to pay for private services, although some health insurance plans may help cover the cost.

Medication Options

Currently, there is no medication that can cure Fragile X. Further, the Food and Drug Administration (FDA) has not approved any drugs specifically for the treatment of Fragile X or its causes. But, in many cases, medications18 have been used to treat many of the symptoms associated with Fragile X, as shown in the table on the next page. Please note that the NICHD does not endorse or support the use of any of these medications in treating symptoms of Fragile X syndrome, or for other conditions for which the medications are not FDA approved.

Medication is most effective when paired with therapy designed to teach new coping skills or behavior. Not every medication helps every child with behavioral symptoms related to Fragile X. Doctors usually prescribe these kinds of medications on a trial basis, to see if they help. If so, the doctor may need to adjust the dose to meet the needs of each child.

This chart is meant for reference ONLY and should not take the place of your health care provider's advice. You should discuss any questions you may have about medication with your health care provider directly.

Some of these medications have serious risks involved with their use; others may make symptoms worse at first or may take several weeks to become effective. Doctors may have to try different dosages or different combinations of medications to find the most effective plan. Families, caregivers, and doctors need to work together to ensure that a medication is working, and that a medication plan is safe.

Symptoms Generic Medications
(brand name in parentheses)
Seizures
Mood instability
  • Carbamazepine (Tegretol)
  • Valproic acid or divalproex (Depakote)
  • Lithium carbonate
  • Gabapentin (Neurontin)
  • Lamotrigine (Lamictal)
  • Topiramate (Topomax), tiagabine (Gabitril), and vigabatrin (Sabril)
  • Phenobarbital and primidone (Mysoline)
  • Attention deficit
    (with or without hyperactivity)
    Hyperarousal
    Sensory over-stimulation
    (often occurs with ADD/ADHD)
    Aggression
    Intermittent explosive disorder
    Obsessive-compulsive disorder
    (often occurs with anxiety and/or depression)
  • Fluoxetine (Prozac)
  • Sertraline (Zoloft) and citalopram (Celexa)
  • Paroxetine (Paxil)
  • Fluvoxamine (Luvox)
  • Risperidone (Risperdal)
  • Quetiapine (Seroquel)
  • Olanzepine (Zyprexa)
  • Sleep disturbances
  • Trazodone
  • Melatonin
  • What are the options for adults who have Fragile X syndrome?

    IDEA requires transition plans for moving from one phase of life to another, and the move from teenager to young adult to adult is no exception. The special services team, which can include family, teachers, a school psychologist, and other developmental specialists, makes the transition plan based on the individual's needs, interests, and skills. These plans may include vocational assessment and training, additional education, supported employment, and community participation. IDEA requires that the plan be in place by the time the individual is 16 years old. The plan will also consider the individual's level of independence to determine what type of living arrangements he or she might benefit from in the future.

    As the teenager with Fragile X gets closer to finishing high school, or to his or her 21st birthday, the structure of his or her day may change to include work/study programs, job-related behavior training, and independent living classes. With the proper treatment and training, a young person with Fragile X may be able to live on his or her own, hold a job, and be an active member of his or her community.

    What should I do if I find out someone in my family has Fragile X syndrome?

    If someone in your family, a child or an adult, is diagnosed with Fragile X, you may also want to be tested to see if you have a mutated FMR1 gene. It is now possible to test for Fragile X in people of any age, as well as before birth. These tests are simple and accurate.

    At present, testing for Fragile X is not done routinely. The tests are often done to help diagnose a child who is developmentally delayed or shows signs of autism or mental retardation.19 Couples who have one or more relatives with mental retardation of unknown cause may also want to be evaluated before deciding to have a child.

    Health care professionals may also recommend an evaluation for Fragile X in a person with one of the following traits:20

    • Any person who has mental retardation of unknown cause, developmental delay, or learning disability
    • Any person with autism or showing autism-like behaviors
    • Any person with a relative who has Fragile X or mental retardation of unknown cause
    • Anyone who was previously assessed for Fragile X using the chromosome test (see description on the next page)
    • Women with premature ovarian failure (POF) or with a family history of POF

    Tests commonly used to diagnose Fragile X

    A number of tests are used to diagnose Fragile X. Each test has its limitations, so in many cases more than one test may be used. The most accurate tests are DNA tests.

    • DNA molecular tests count the number of CGG repeats in the promoter region of the FMR1 gene and check to see if the gene is methylated (inactive). These tests are used most often to diagnose Fragile X. The two main DNA tests include:
      • Southern Blot studies how quickly DNA pieces move through a liquid or gel when exposed to electricity. Although good at finding large numbers of repeats and determining methylation, this process is rather slow.
      • Polymerase Chain Reaction (PCR) multiplies the amount of DNA being tested so it can be analyzed more quickly. Although it can miss some large repeat mutations, this test is much faster to perform and is very good at detecting small and medium-sized repeat segments.
    • Chromosome test looks for the "broken" area of a chromosome using a microscope. Because this test is older, costly, and often inaccurate, it is recommended that another type of test be used to diagnose Fragile X. The DNA test is needed to confirm the diagnosis.
    • Protein test measures the amount of FMRP produced by living cells. This test is useful for screening large groups of people for Fragile X. In the future, this test may be helpful in evaluating how severe an FMR1 mutation is. The DNA test is needed to confirm the diagnosis.

    Prenatal testing for families who are at risk

    A pregnant woman who has characteristics that place her at risk for Fragile X, such as features of Fragile X or a family history that suggests the presence of Fragile X, may want to have a prenatal test. During such a test, the doctor either takes a sample of amniotic fluid, a process called amniocentesis, or takes a sample of cells from the placenta, a process called chorionic villus sampling. Then the cells are sent to a lab, where they go through one of the methods used to diagnose Fragile X. Cells that contain a larger number of CGG repeats would be diagnosed as having Fragile X.

    These tests can be done on many different types of body tissues. In most cases, a simple blood test provides the cells needed. But cells from hair roots and from inside the cheek can also be used. If you or one of your family members wants to be tested, talk to your health care provider. He or she will likely take a sample of your blood and send it to a lab. The results will come back in a number of weeks. For more information on tests for Fragile X and their features, please refer to the Additional Resources section.

    What is being done to develop treatments or a cure for Fragile X syndrome?

    Since the late 1960s, the NICHD has supported the research of scientists who are trying to understand Fragile X. The work of these scientists continues to increase knowledge about this disorder, but many questions still remain unanswered.

    In 1991, researchers funded by the NICHD identified FMR1 as the gene that, when mutated, causes Fragile X. Since that time, the NICHD has been a major source of funds for Fragile X research. In addition, a number of private, non-profit organizations, including the FRAXA Research Foundation, the National Fragile X Foundation, and the Conquer Fragile X Foundation, are also dedicated to continuing Fragile X research and to raising awareness of the disorder.

    In the Children's Health Act of 2000, congress authorized the NICHD to create and maintain at least three research centers specifically for Fragile X research. In March 2003, the NICHD announced awards for the following Mental Retardation and Developmental Disabilities Research Centers to house the new Fragile X Research Centers: the University of North Carolina, in affiliation with the University of Kansas; the University of Washington; and Baylor College of Medicine. The efforts of these new centers began in late spring 2003.

    Also in 2000, the NICHD initiated, with financial collaboration from the FRAXA Research Foundation and the National Institute of Mental Health, a special research program to support noted scientists around the world in an effort to find treatments and a cure for Fragile X.

    Some of these researchers are examining Fragile X at the molecular level. Some of the questions they are asking include:

    • Why does the FMR1 gene have an increased number of CGG repeats in the promoter region?
    • What causes the increased methylation of the promoter region, which blocks the gene from producing FMRP?
    • What is the role of FMRP in the brain?
    • How does FMRP help other proteins, and what are the functions of those proteins?

    The findings from such research may help to prevent or reverse mental retardation and other symptoms of Fragile X.

    To advance the field of Fragile X research, scientists are also working to create models of how the human brain works. Some are creating computer programs that imitate the way the human brain learns and remembers. Other scientists modify genes in other animals, such as mice and fruit flies, to try new interventions or treatments. For instance, researchers can replace the FMR1 gene in a normal mouse with a mutated human FMR1 gene. Such "transgenic" animals are key to much of the current research. For example, one recent study is examining the effects of a certain substance in transgenic mice that don't produce FMRP. Researchers believe that this compound could help regulate brain processes that are impacted by a lack of FMRP. Using these mice, researchers can test this new intervention to ensure that it is safe and effective before the intervention is used with humans.

    Can we prevent or cure Fragile X? Two decades ago, researchers might have said "No." Now scientists are exploring several promising possibilities, including:

    • Gene repair, gene reactivation, and gene therapy. Scientists may be able to induce certain brain chemicals to repair defective FMR1 genes. Researchers also seek ways to prevent or reverse methylation, the process that interferes with the instructions for making FMRP and inactivates the FMR1 gene. Still other scientists are trying to determine if it is possible to replace defective genes with stable, working copies of the FMR1 gene. This type of gene research involves a number of challenges. First, it is important that researchers learn how many cells are needed to produce the right amount of protein. Too much of the protein may be as harmful as too little, so finding the right balance is crucial. Another difficulty lies in targeting only the defective FMR1 genes for repair or reactivation, without affecting other healthy genes. Further, replacing genes, especially those involved in brain function, carries additional problems and risks. However, researchers continue to pursue these avenues. NICHD-supported and other sponsored research is already underway to study the possibility of reversing methylation on the FMR1 promoter sequence, prenatally. Success in this area may allow scientists to "reactivate" FMRP production before a child is born. Other gene research is also underway
    • Protein replacement. Scientists already make FMRP in the lab. At present, however, they are unable to get FMRP to the brain, partly because the FMRP molecule is too large to pass through the structures that protect the brain. Someday people with Fragile X may be able to take a pill or injection of FMRP to relieve many of the symptoms of Fragile X.
    • Protein substitute through medication. Scientists may be able to use other substances to take the place of FMRP in certain brain processes. Using these substitutes, brain processes and other functions of FMRP may be able to occur normally. For example, new drugs may be able to regulate processes in the brain, like communication between neurons, that seem to be affected by low levels of FMRP.

    While these research avenues are promising, none of them has progressed enough to provide immediate help to someone with Fragile X. Parents, families, and caregivers should work together with health care professionals, educators, and therapists to ensure that those affected by Fragile X receive the care that they need.

    This is an exciting time in Fragile X research. Dr. James Watson, who received the Nobel Prize in Physiology or Medicine for the co-discovery of the double-helix structure of DNA, believes that science will be able to defeat the negative effects of Fragile X. He predicts, "Our wealth of research strategies and technologies may soon lead to new forms of therapy and medication. Someday we may be able to prevent the mental retardation and other symptoms of Fragile X."

    Where can I go for more information about Fragile X syndrome?

    The National Institute of Child Health and Human Development (NICHD)

    The mission of the NICHD is to ensure that every person is born healthy and wanted, that women suffer no harmful effects from reproductive processes, and that all children have the chance to achieve their full potential for healthy and productive lives, free from disease or disability, and to ensure the health, productivity, independence, and well-being of all people through optimal rehabilitation. The NICHD Information Resource Center is your one-stop source for NICHD brochures, booklets, and other materials related to the health of children, adults, families, and populations.

    You can contact the NICHD Information Resource Center at

    Mail: P.O. Box 3006, Rockville, MD 20847
    Phone: 1-800-370-2943
    Fax: 301-984-1473
    E-mail: NICHDInformationResourceCenter
    @mail.nih.gov

    Internet: www.nichd.nih.gov

    National organizations

    The following organizations of families affected by Fragile X are excellent sources of practical information and support. Each of these organizations publishes a newsletter with up-to-date information about current research, conferences, and legislation.

    Additional Resources

    • The ARC of the United States-1010 Wayne Avenue, Suite 650, Silver Spring, MD 20910; 301-565-3842; fax 301-565-3843; www.thearc.org.
    • American Association on Mental Retardation-444 North Capitol Street, NW, Suite 846, Washington, DC 20001-1512; 202-387-1968 or 800-424-3688; fax 202-387-2193; www.aamr.org.
    • Association of University Centers on Disabilities-8630 Fenton Street, Suite 410, Silver Spring, MD 20910; 301-588-8252; fax 301-588-2842; www.aucd.org.
    • The Dolan DNA Learning Center, Cold Spring Harbor Laboratory provides clear explanations of the cause, diagnosis, and treatment of Fragile X; www.dnalc.org.
    • GeneTests Web site. Funded in part by the National Library of Medicine at the NIH, the Web site provides information on genetic disorders, testing, and contact information for clinical laboratories that do genetic tests; www.genetests.org.
    • American Academy of Pediatrics. (1996). Policy Statement: Health Supervision for Children with Fragile X Syndrome. Pediatrics 98(2):297-300. Available online at www.aap.org/policy/01493.html.

    Medically reviewed by Edward Spence, MD; American Board of Pediatrics and American Board of Medical Genetics with subspecialties in Clinical Genetics, Clinical Biochemical Genetics, Clinical Molecular Genetics

    Last update: 3/27/2008

    SOURCE: National Institute of Child Health and Human Development(NICHD)

    1 Harris-Schmidt, G. Characteristics of Cognitive Development. National Fragile X Foundation. Available at www.fragilex.org/html/cognitive.htm. Web site last modified April 1, 2003.
    2 Finucane, B.; McConkie-Rosell, A.; and Cronister, A. (2002). Fragile X Syndrome: A Handbook for Families and Professionals (Newburyport, MA: The National Fragile X Foundation).
    3 Crawford, D.C.; Acuña, J.M.; and Sherman, S.L. (2001). FMR1 and the Fragile X Syndrome: Human Genome Epidemiology Review. Genetics in Medicine 3(5):359-371.
    4 From the Your Genes, Your Health Web site, Dolan DNA Learning Center, Cold Spring Harbor Laboratory; www.yourgenesyourhealth.org/ygyh/
    mason/ygyh.html? syndrome=fragx
    .
    5 Crawford, D.C.; Acuña, J.M.; and Sherman, S.L. (2001). FMR1 and the Fragile X Syndrome: Human Genome Epidemiology Review. Genetics in Medicine 3(5):359-371.
    6 From the FRAXA Web site (www.FRAXA.org): Bailey, D.B., and Nelson, D. (1995). The Nature and Consequences of Fragile X Syndrome. Mental Retardation and Developmental Disabilities Research Reviews 1:238-244.
    7 American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (Washington, DC: American Psychiatric Association).
    8 Hagerman, R. (2001). Meeting the Challenge of Fragile X Syndrome. Patient Care 31(14).
    9 Harris-Schmidt, G. What Are Some Important Teaching Strategies? National Fragile X Foundation. Available at www.fragilex.org/html/teaching.htm. Web site last modified April 1, 2003.
    10 Hagerman, R.J.; Leehy, M.; Heinrichs, W.; et al. (2001). Intention Tremor, Parkinsonism, and Generalized Brain Atrophy in Male Carriers of Fragile X. Neurology 57(1):127-130.
    11 Allingham-Hawkins, D.J.; Babul-Hirji, R.; Chitayat, D.; et al. (1999). Fragile X Premutation is a Significant Risk Factor for Premature Ovarian Failure: The International Collaborative POF in Fragile X Study-Preliminary Data. American Journal of Medical Genetics 83(4):322-325.
    12 Uzielli, M.L.; Guarducci, S.; Lapi, E.; et al. (1999). Premature Ovarian Failure (POF) and Fragile X Premutation Females: From POF to Fragile X Carrier Identification, from Fragile X Carrier Diagnosis to POF Association Data. American Journal of Medical Genetics 84(3):300-303.
    13 American College of Obstetricians and Gynecologists (2000). The Menopause Years (Washington, DC: American College of Obstetricians and Gynecologists).
    14 Bailey, D.B., Jr.; Hatton, D.D.; Mesibov, G.; Ament, N.; and Skinner, M. (2000). Early Development, Temperament, and Functional Impairment in Autism and Fragile X Syndrome. Journal of Autism and Developmental Disorders 30(1):49-59.
    15 Rogers, S.J.; Wehner, D.E.; and Hagerman, R. (2001). The Behavioral Phenotype in Fragile X: Symptoms of Autism in Very Young Children With Fragile X Syndrome, Idiopathic Autism, and Other Developmental Disorders. Developmental and Behavioral Pediatrics 22(6):409-417.
    16 Bauchwitz, R.P. (2000). Biomolecular Approaches to Fragile X Syndrome Therapy. Available at http://www.fragilex.org/BIOMOLECULAR_APPROACHES_TO_
    FRAGILE_X_SYNDROME_THERAPY.pdf
    .
    17 Hagerman, R.J.; and Hagerman, P.J. (eds.) (2002). Fragile X Syndrome: Diagnosis, Treatment, and Research, Third Edition (Baltimore, MD: Johns Hopkins University Press).
    18 Adapted from http://www.fragilex.org/html/pharmacotherapy.htm Web site last updated May 2002.
    19 Prows, C.A., and Lovell, A.M. (1998). Ask the Expert. Genetic Testing for Fragile X. Journal of the Society for Pediatric Nurses 3(14):161-166.< br /> 20 American College of Medical Genetics (1994). Fragile X Syndrome: Diagnosis and Carrier Testing. Working Group of the Genetic Screening Subcommittee of the Clinical Practice Committee. American College of Medical Genetics. Ameican Journal of Medical Genetics 53(4):380-381.

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    Reviewed on 3/27/2008
    References
    Medically reviewed by Edward Spence, MD; American Board of Pediatrics and American Board of Medical Genetics with subspecialties in Clinical Genetics, Clinical Biochemical Genetics, Clinical Molecular Genetics

    Last update: 3/27/2008

    SOURCE: National Institute of Child Health and Human Development(NICHD)

    1 Harris-Schmidt, G. Characteristics of Cognitive Development. National Fragile X Foundation. Available at www.fragilex.org/html/cognitive.htm. Web site last modified April 1, 2003.
    2 Finucane, B.; McConkie-Rosell, A.; and Cronister, A. (2002). Fragile X Syndrome: A Handbook for Families and Professionals (Newburyport, MA: The National Fragile X Foundation).
    3 Crawford, D.C.; Acuña, J.M.; and Sherman, S.L. (2001). FMR1 and the Fragile X Syndrome: Human Genome Epidemiology Review. Genetics in Medicine 3(5):359-371.
    4 From the Your Genes, Your Health Web site, Dolan DNA Learning Center, Cold Spring Harbor Laboratory; www.yourgenesyourhealth.org/ygyh/
    mason/ygyh.html? syndrome=fragx
    .
    5 Crawford, D.C.; Acuña, J.M.; and Sherman, S.L. (2001). FMR1 and the Fragile X Syndrome: Human Genome Epidemiology Review. Genetics in Medicine 3(5):359-371.
    6 From the FRAXA Web site (www.FRAXA.org): Bailey, D.B., and Nelson, D. (1995). The Nature and Consequences of Fragile X Syndrome. Mental Retardation and Developmental Disabilities Research Reviews 1:238-244.
    7 American Psychiatric Association (2000). Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (Washington, DC: American Psychiatric Association).
    8 Hagerman, R. (2001). Meeting the Challenge of Fragile X Syndrome. Patient Care 31(14).
    9 Harris-Schmidt, G. What Are Some Important Teaching Strategies? National Fragile X Foundation. Available at www.fragilex.org/html/teaching.htm. Web site last modified April 1, 2003.
    10 Hagerman, R.J.; Leehy, M.; Heinrichs, W.; et al. (2001). Intention Tremor, Parkinsonism, and Generalized Brain Atrophy in Male Carriers of Fragile X. Neurology 57(1):127-130.
    11 Allingham-Hawkins, D.J.; Babul-Hirji, R.; Chitayat, D.; et al. (1999). Fragile X Premutation is a Significant Risk Factor for Premature Ovarian Failure: The International Collaborative POF in Fragile X Study-Preliminary Data. American Journal of Medical Genetics 83(4):322-325.
    12 Uzielli, M.L.; Guarducci, S.; Lapi, E.; et al. (1999). Premature Ovarian Failure (POF) and Fragile X Premutation Females: From POF to Fragile X Carrier Identification, from Fragile X Carrier Diagnosis to POF Association Data. American Journal of Medical Genetics 84(3):300-303.
    13 American College of Obstetricians and Gynecologists (2000). The Menopause Years (Washington, DC: American College of Obstetricians and Gynecologists).
    14 Bailey, D.B., Jr.; Hatton, D.D.; Mesibov, G.; Ament, N.; and Skinner, M. (2000). Early Development, Temperament, and Functional Impairment in Autism and Fragile X Syndrome. Journal of Autism and Developmental Disorders 30(1):49-59.
    15 Rogers, S.J.; Wehner, D.E.; and Hagerman, R. (2001). The Behavioral Phenotype in Fragile X: Symptoms of Autism in Very Young Children With Fragile X Syndrome, Idiopathic Autism, and Other Developmental Disorders. Developmental and Behavioral Pediatrics 22(6):409-417.
    16 Bauchwitz, R.P. (2000). Biomolecular Approaches to Fragile X Syndrome Therapy. Available at http://www.fragilex.org/BIOMOLECULAR_APPROACHES_TO_
    FRAGILE_X_SYNDROME_THERAPY.pdf
    .
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    18 Adapted from http://www.fragilex.org/html/pharmacotherapy.htm Web site last updated May 2002.
    19 Prows, C.A., and Lovell, A.M. (1998). Ask the Expert. Genetic Testing for Fragile X. Journal of the Society for Pediatric Nurses 3(14):161-166.< br /> 20 American College of Medical Genetics (1994). Fragile X Syndrome: Diagnosis and Carrier Testing. Working Group of the Genetic Screening Subcommittee of the Clinical Practice Committee. American College of Medical Genetics. Ameican Journal of Medical Genetics 53(4):380-381.

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