Fragile X Syndrome and Autism Spectrum Disorders
This disorder is the most common inherited form of mental retardation. It was so named because one part of the
X chromosome has a defective piece that appears pinched and fragile when under a microscope. Fragile X
syndrome affects about 2 to 5 percent of people with autism spectrum disorder. It is important to have a child with
autism spectrum disorder checked for Fragile X, especially if the parents are considering having another child. For
an unknown reason, if a child with autism spectrum disorder also has Fragile X, there is a one-in-two chance that
boys born to the same parents will have the syndrome. Other members of the family who may be contemplating
having a child may also wish to be checked for the syndrome.
What Are the Common Symptoms of Fragile X?
Features usually include:
Boys are typically more severely affected than girls. While most boys have mental retardation, only one-third to one-
half of girls have significant intellectual impairment; the rest have either normal IQ or learning disabilities. Math is
often a particular challenge for girls. Emotional and behavioral problems are common in both sexes.
About 20% of boys with fragile X meet full criteria for autism. Most boys and some girls have some symptoms of
autism, but many tend to be very social and interested in other people.
Just One Gene
In 1991, scientists discovered the gene (called FMR1 for "Fragile X Mental Retardation - 1") that causes fragile X. In
people with Fragile X, a defect in FMR1 (a "full mutation") shuts the gene down. Like a defective factory, FMR1
cannot manufacture the protein that it normally makes.
Other individuals are carriers: they have a small defect in FMR1 (called a "premutation") but do not show
symptoms.
Fragile X is inherited. Carrier men pass the premutation to all their daughters but none of their sons. Each child of
a carrier woman has a 50% chance of inheriting the gene defect. The Fragile X premutation can be passed silently
down through generations in a family before a child is affected by the syndrome.
The Fragile X Gene
The FMR1 gene is located on the long arm of the X chromosome. At the start of this gene lies a region of DNA
which varies in length from one person to another. Ordinarily, this stretch of DNA falls within a range of length that
would be considered "normal".
In some people, however, this stretch of DNA is somewhat longer; this gene change is called a "premutation".
Although a person who carries the premutation does not typically have symptoms of Fragile X, the stretch of DNA
is prone to further expansion when it is passed from a woman to her children. When the stretch of DNA expands
beyond a certain length, the gene is switched off and does not produce the protein that it is normally makes. This
gene change is called a "full mutation".
A male who inherits a full mutation exhibits Fragile X syndrome because his only X chromosome contains the
mutated gene. A female may not be as severely affected because each cell of her body needs to use only one of
its two X chromosomes and randomly inactivates the other.
How is Fragile X inherited?
Each cell in the body contains forty-six (twenty-three pairs of) chromosomes. These chromosomes consist of
genetic material (DNA) necessary for the proteins which lead to growth, development and physical and intellectual
characteristics.
The first twenty-two pairs of chromosomes are the
same in males and females. The remaining two
chromosomes, X and Y, determine whether a person
is male or female.
Males have only one X chromosome which is inherited fromthe mother. They receive a Y chromosome from the
father. Females inherit two X chromosomes, one from each parent.
How common is Fragile X?
Fragile X syndrome is the most common inherited cause of mental impairment and the most common known
cause of autism. Fragile X affects 1 in 4000 males and 1 in 6000 females of all races and ethnic groups (source
Centers for Disease Control). About 1 in 259 women carry fragile X and could pass it to their children. About 1 in
800 men carry fragile X; their daughters will also be carriers.
Large-scale population studies of fragile X still need to be done, but it is clear that this is one of the most common
genetic diseases in humans. Most people with fragile X are not yet correctly diagnosed.
Is There a Test for Fragile X?
A DNA test for Fragile X was developed in 1992. This blood test is accurate and can detect both carriers and fully-
affected individuals. It can be ordered by any physician; the blood sample is then sent to a lab that offers the test. It
usually takes several weeks to get the results.
Because the symptoms of Fragile X can be subtle, especially in young children, and because it is so frequent in
the general population (1 in 4000 males and 1 in 6000 females), Fragile X testing should be considered for any
individual with otherwise unexplained developmental delay or mental retardation.
Most major U.S. medical centers offer the Fragile X test. It costs several hundred dollars but may be covered by
health insurance. For more information about testing, talk to your doctor or genetic counselor.
April 2005: Standard Reference Material from the National Institute of Standards and Technology (NIST) was
released to help clinical genetics labs improve the accuracy of Fragile X diagnostic tests.
Are there any Treatments?
There is currently no cure for Fragile X, although appropriate education and medications can help maximize the
potential of each child. However, most boys and many girls remain significantly affected throughout their lives. The
cost to society for treatment, special education, and lost income is staggering. The need for research aimed at
treatment is urgent.
FRAXA-funded research has already achieved significant breakthroughs in understanding Fragile X. We now know
that the FMR protein's normal role is to help shape the connections between neurons (brain cells) that underlie
learning and memory, and we are beginning to understand how the lack of the protein causes Fragile X syndrome.
Because absence of the FMR protein seems to delay the development of neurons, rather than damage or destroy
them, it appears likely that treatments now being investigated can potentially benefit all individuals with Fragile X,
regardless of age.
This disorder is the most common inherited form of mental retardation. It was so named because one part of the
X chromosome has a defective piece that appears pinched and fragile when under a microscope. Fragile X
syndrome affects about 2 to 5 percent of people with autism spectrum disorder. It is important to have a child with
autism spectrum disorder checked for Fragile X, especially if the parents are considering having another child. For
an unknown reason, if a child with autism spectrum disorder also has Fragile X, there is a one-in-two chance that
boys born to the same parents will have the syndrome. Other members of the family who may be contemplating
having a child may also wish to be checked for the syndrome.
- FACT: For between 2% and 6% of all children diagnosed with autism, the cause is the Fragile X gene
mutation. - FACT: Approximately one-third of all children diagnosed with fragile X syndrome also have some degree
of autism. - FACT: Fragile X syndrome is the most common known single gene cause of autism
What Are the Common Symptoms of Fragile X?
Features usually include:
- mental impairment, ranging from learning disabilities to mental retardation
- attention deficit and hyperactivity
- anxiety and unstable mood
- autistic behaviors
- long face, large ears, flat feet
- hyperextensible joints, especially fingers
- Seizures (epilepsy) affect about 25% of people with fragile X
Boys are typically more severely affected than girls. While most boys have mental retardation, only one-third to one-
half of girls have significant intellectual impairment; the rest have either normal IQ or learning disabilities. Math is
often a particular challenge for girls. Emotional and behavioral problems are common in both sexes.
About 20% of boys with fragile X meet full criteria for autism. Most boys and some girls have some symptoms of
autism, but many tend to be very social and interested in other people.
Just One Gene
In 1991, scientists discovered the gene (called FMR1 for "Fragile X Mental Retardation - 1") that causes fragile X. In
people with Fragile X, a defect in FMR1 (a "full mutation") shuts the gene down. Like a defective factory, FMR1
cannot manufacture the protein that it normally makes.
Other individuals are carriers: they have a small defect in FMR1 (called a "premutation") but do not show
symptoms.
Fragile X is inherited. Carrier men pass the premutation to all their daughters but none of their sons. Each child of
a carrier woman has a 50% chance of inheriting the gene defect. The Fragile X premutation can be passed silently
down through generations in a family before a child is affected by the syndrome.
The Fragile X Gene
The FMR1 gene is located on the long arm of the X chromosome. At the start of this gene lies a region of DNA
which varies in length from one person to another. Ordinarily, this stretch of DNA falls within a range of length that
would be considered "normal".
In some people, however, this stretch of DNA is somewhat longer; this gene change is called a "premutation".
Although a person who carries the premutation does not typically have symptoms of Fragile X, the stretch of DNA
is prone to further expansion when it is passed from a woman to her children. When the stretch of DNA expands
beyond a certain length, the gene is switched off and does not produce the protein that it is normally makes. This
gene change is called a "full mutation".
A male who inherits a full mutation exhibits Fragile X syndrome because his only X chromosome contains the
mutated gene. A female may not be as severely affected because each cell of her body needs to use only one of
its two X chromosomes and randomly inactivates the other.
How is Fragile X inherited?
Each cell in the body contains forty-six (twenty-three pairs of) chromosomes. These chromosomes consist of
genetic material (DNA) necessary for the proteins which lead to growth, development and physical and intellectual
characteristics.
The first twenty-two pairs of chromosomes are the
same in males and females. The remaining two
chromosomes, X and Y, determine whether a person
is male or female.
Males have only one X chromosome which is inherited fromthe mother. They receive a Y chromosome from the
father. Females inherit two X chromosomes, one from each parent.
How common is Fragile X?
Fragile X syndrome is the most common inherited cause of mental impairment and the most common known
cause of autism. Fragile X affects 1 in 4000 males and 1 in 6000 females of all races and ethnic groups (source
Centers for Disease Control). About 1 in 259 women carry fragile X and could pass it to their children. About 1 in
800 men carry fragile X; their daughters will also be carriers.
Large-scale population studies of fragile X still need to be done, but it is clear that this is one of the most common
genetic diseases in humans. Most people with fragile X are not yet correctly diagnosed.
Is There a Test for Fragile X?
A DNA test for Fragile X was developed in 1992. This blood test is accurate and can detect both carriers and fully-
affected individuals. It can be ordered by any physician; the blood sample is then sent to a lab that offers the test. It
usually takes several weeks to get the results.
Because the symptoms of Fragile X can be subtle, especially in young children, and because it is so frequent in
the general population (1 in 4000 males and 1 in 6000 females), Fragile X testing should be considered for any
individual with otherwise unexplained developmental delay or mental retardation.
Most major U.S. medical centers offer the Fragile X test. It costs several hundred dollars but may be covered by
health insurance. For more information about testing, talk to your doctor or genetic counselor.
April 2005: Standard Reference Material from the National Institute of Standards and Technology (NIST) was
released to help clinical genetics labs improve the accuracy of Fragile X diagnostic tests.
Are there any Treatments?
There is currently no cure for Fragile X, although appropriate education and medications can help maximize the
potential of each child. However, most boys and many girls remain significantly affected throughout their lives. The
cost to society for treatment, special education, and lost income is staggering. The need for research aimed at
treatment is urgent.
FRAXA-funded research has already achieved significant breakthroughs in understanding Fragile X. We now know
that the FMR protein's normal role is to help shape the connections between neurons (brain cells) that underlie
learning and memory, and we are beginning to understand how the lack of the protein causes Fragile X syndrome.
Because absence of the FMR protein seems to delay the development of neurons, rather than damage or destroy
them, it appears likely that treatments now being investigated can potentially benefit all individuals with Fragile X,
regardless of age.
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