Families and
 

Fragile Syndrome
 

U.S. DEPARTMENT OF HEALTH AND HUMAN SERVICES 

PUBLIC HEALTH SERVICE
 

NATIONAL INSTITUTES OF HEALTH
 
Dear families— 

Welcome to the National Institute of Child Health and Human Development (NICHD) family album about Fragile X syndrome. 

As a health research agency, the NICHD family includes not only scientists, researchers, and health care providers, but also 

children, adults, and families who benefit from health research advances. 

Finding out that your child, a member of your family, or a friend has a “syndrome” can raise some tough questions. What 

does having that syndrome mean for the individual? What special needs will this individual have? How will those needs 

affect my family? Will my child, family member, or friend be able to take part in everyday activities and important events? 

Through its research, the NICHD strives to find answers to these questions. This booklet is designed to give you and your family 

some general information about Fragile X syndrome, its causes, its features, and its treatments. This publication also describes 

some of the research directions currently underway to learn more about Fragile X. 

The information presented here will give you and your family a foundation of knowledge that will help in understanding options, 

making decisions, and finding help. 

As you read, you’ll notice many photographs of members of the NICHD family. These people are not models or actors. They 

are individuals with Fragile X syndrome and their families. Through these images, you’ll see that even though Fragile X affects 

families, it doesn’t keep them from doing things that all families do—laughing, sharing, encouraging, and loving. 

I hope this booklet will help your family move forward in meeting the challenges of Fragile X syndrome together. 

Sincerely yours, 

Duane Alexander, M.D. 

Director, NICHD 
Table of Contents 

What is Fragile X syndrome? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
 

What causes Fragile X syndrome? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
 

What keeps the FMR1 gene from producing FMRP in Fragile X syndrome? . . . . . . . . . . . . . . . . . . . . . . . . . . . . 4
 

Human cells 101 . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 8
 

How many people are affected by Fragile X syndrome? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
 

How is Fragile X syndrome inherited? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 12
 

What are the signs and symptoms of Fragile X syndrome? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 14
 

Intelligence and learning . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 15
 

Physical . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
 

Social and emotional . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 19
 

Speech and language . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 20
 

Sensory . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 22
 

Is there a cure for Fragile X syndrome? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
 

Are there treatments for Fragile X syndrome? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
 

Educational options . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 24
 

Therapeutic options . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 27
 

Medication options . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
 

What are the options for adults who have Fragile X syndrome? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 32
 

What should I do if I find out someone in my family has Fragile X syndrome? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 34
 

What is being done to develop treatments or a cure for Fragile X syndrome? . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 38
 

Where can I go for more information about Fragile X syndrome?. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
 

The National Institute of Child Health and Human Development (NICHD) . . . . . . . . . . . . . . . . . . . . . . . . . . . 42
 

National organizations . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
 

Additional resources . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 44
 

References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 45
 
1 

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 booklet uses that term to describe some features related to Fragile X syndrome. For more information, please see the Additional Resources section of this booklet. 
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? 

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, the 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. 

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. 

2 3 
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.” 

4 5 

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. 

* The number of repeats and their effects are still being studied. At the time this booklet 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. 

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: 

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. 
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. 

6	 7
 
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. 

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). 

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. 

8 9
 
10 11 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.* 

A summary of existing research5 conducted by the Centers for Disease Control and Prevention in 2001 estimated 

that approximately one in 3,500 to 8,900 males is affected by the full mutation of the FMR1 gene, and that one 

in 1,000 males has the premutation form of the FMR1 gene. This study also estimated that one in 250 to 500 

females in the general population has the premutation. Another study6 estimated that one in 4,000 females is 

affected by the full mutation. 

Although these estimates are useful in trying to understand the impact of Fragile X on various communities, 

keep in mind that these numbers are only the best estimates based on the available information. Many factors 

can affect the completeness and/or accuracy of the available information, which means that the number of people 

affected by Fragile X could actually be 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. 

* The number of people affected by a full mutation or a premutation of the FMR1 gene is still being studied. At the time this booklet was printed, few population-based studies had been 

done to determine exactly how many people were affected by Fragile X. The estimates included here from Crawford, Acuña, and Sherman differ from other estimates, including those 

provided by many of the national organizations dedicated to Fragile X (Bailey & Nelson, The Nature and Consequences of Fragile X Syndrome, Mental Retardation and Developmental 

Disabilities Research Reviews, 1:238-244, 1995; Prevalence of Fragile X Revisited and Revised, The National Fragile X Foundation Quarterly; Winter, 2002). 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 booklet. 
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. 

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). 

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. 

12 13
 
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 

Now consider each category in more detail. 

14 15 

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. 

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. 

•	 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. 

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. 

16	 17
 
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 booklet 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.) 

18 19 
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. 

20 21
 
Sensory 

Many children with Fragile X are sensitive to certain sensations. 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. 

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 percent 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 percent6 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 booklet, 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. 

22 23
 
Although research continues and knowledge about Fragile X 

and its characteristics grows, there is no cure for 

Fragile X at this time. 

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. 

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. 

24 25
 
A child with Fragile X should be evaluated and reevaluated 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 

26	 27
 
28 29

• 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. 

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) 

• Phenytoin (Dilantin) 

Attention deficit 

(With or without hyperactivity) 

• Methylphenidate (Ritalin, Concerta) and 

dexamethamphetamine (Adderall, 

Dexedrine) 

• L-acetylcarnitine 

• Venlafaxine (Effexor) and nefazodone 

(Serzone) 

• Amantadine (Symmetrel) 

• Folic acid 

Hyperarousal 

Sensory over-stimulation 

(Often occurs with ADD/ADHD) 

• Clonidine (Catapres TTS patches) 

• Guanfacine (Tenex) 

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 • Trazadone 

• Melatonin 

30 31
 
I

DEA 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. 

32 33
 
34 35 

I

f 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 autistim-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 

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. 
36 37 

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 of this booklet. 

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. 
38 39 

S

ince 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. 
40 41 

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.” 
42 43

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 the reproductive process, and that all children have the chance to fulfill their potential for 

a healthy and productive life, free of disease or disability. 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. 

FRAXA Research Foundation 

Run by parents, 

relatives, and friends 

of those with Fragile X, 

as well as by medical professionals. 

Promotes and funds scientific research 

aimed at the treatment and cure of 

Fragile X. Publishes a newsletter and 

other materials, including a CD-ROM, 

about Fragile X; maintains a Web site and 

a listserv about Fragile X; and organizes 

advocacy and fundraising events around 

the country. 

Mail: 45 Pleasant Street 

Newburyport, MA 01950 

Phone: 978-462-1866 

Fax: 978-463-9985 

E-mail: info@fraxa.org 

Internet: www.fraxa.org 

National Fragile X Foundation 

Provides information and 

support to individuals with 

Fragile X, their families, 

educators, and health professionals. 

Sponsors conferences and publishes a 

quarterly newsletter. Offers a list of 

print and other media materials about 

Fragile X for children, families, and 

health care professionals. Offers 

telephone consultation and referrals to 

medical and genetic services. Contains 

detailed information on its Web site 

about the causes and treatment of 

Fragile X and about Fragile X research. 

Also provides information in Spanish. 

Mail: P.O. Box 190488 

San Francisco, CA 94119-0488 

Phone: 800-688-8765 

Fax: 925-938-9315 

E-mail: NATLFX@FragileX.org 

Internet: www.fragilex.org 

Conquer Fragile X Foundation 

Seeks to create strong, 

dynamic linkages 

between Fragile X 

researchers in the United States and those 

abroad. Supports Fragile X research 

projects and encourages creative 

approaches to strengthen the body of 

Fragile X research through cooperation 

and coordination of research efforts. 

Mail: 450 Royal Palm Way 

Suite 400 

Palm Beach, FL 33480 

Phone: 561-842-9219 

Fax: 877-275-1192 

E-mail: mail@cfxf.org 

Internet: www.cfxf.org 
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. 

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. 

44	 45
 
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. 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. 

Acknowledgements 

The NICHD would like to thank: Donald Bailey, Gary Bassell, Robert Bauchwitz, David and Mary Beth Busby, Katie Clapp, 

Jennifer Darnell, Randi Hagerman, Robert Miller, Mario Rattazzi, Stephanie Sherman, Mike Tranfaglia, and Stephen Warren. 

Some photographs on pages ii, 7, 19, 21, 27, 29, 32, 33, 34, and 37 by Franklin Avery Photography, courtesy of the National 

Fragile X Foundation. All other photographs by Tina Williams Photography. 

Based on a manuscript by Sharyn Neuwirth. 

46 
National Institute of Child 

Health and Human 

Development (NICHD) 

NIH Publication No. 96-3402 

Revised 2003