Fragile X Syndrome

ANN MARY TONY
GROUP: 7
What is FRAGILE X SYNDROME?
Fragile X syndrome is the most common form of

inherited mental retardation. Individuals with this
condition have developmental delay variable levels of
mental retardation,and behavioral and emotional
difficulties. They may also have characteristic physical
traits. Generally, males are affected with moderate
mental retardation and females with mild mental
retardation.
The mutation involves an expansion in a region of

the gene that typically contains about 29 or 30
repetitions of a specific pattern of molecules
(i.e., cytosine, guanine, and guanine, or "CGG") The
number of repetitions of the pattern is referred to
as "CGG repeats." If a person has 6 CGG repeats ,
the sequence of these molecules in his/her DNA
would be CGG CGG CGG CGG CGG CGG.
Individuals with between 6 and 40 repetitions of
the CGG pattern are considered to have a normal
gene. Those with more that 200 CGG repeats have
the "full mutation," which causes fragile X
syndrome, the most severe of the conditions
known to be associated with the FMR1 gene.
FRAGILE X SYNDROME - A Single Gene Disorder

Fragile X Syndrome is a single gene disorder
located on the X chromosome. Understanding the basics of fragile X
syndrome requires an understanding of how genes themselves are
constructed and what they do.
Fragile X syndrome results from a mutation (a change in the typical
DNA sequence) known as trinucleotide repeat expansion. This
means that a series of three particular nucleotides (CGG) in the
DNA is greatly expanded beyond its normal size, disrupting the
normal messages that need to be sent.This fact was discovered in
1991 by several teams of researchers studying the X chromosome.
In the FMR-1 gene located on the EDX chromosome , most individuals

. CGG repeat that occurs between 5 and 50 times ,
have
the average being around thirty.
These individuals are normal with respect to fragile X syndrome, and usually
carry no risk of transmitting it, although the 4060 repeat range is sometimes
considered a "gray zone" which may or may not be unstable (have a risk of
expanding).
Some individuals have CGG sequences that are repeated in the
range of about 50 to 200. These individuals are generally referred to as
premutation carriers. This means that they carry the syndrome and can
transmit it to their children. Premutation carriers, however, are not usually
affected by fragile X syndrome. When the number of CGG repeats expands
beyond 200, the individual usually has the full mutation.
This means that they have fragile X syndrome and will experience the
impairments and delays associated with the syndrome.
1. The FMR-1 gene is located on the X chromosome.

This gene is responsible for instructing the cell to make FMRP,
a protein assumed to be essential for normal brain functioning.
X - chromosome
FMR-1 Gene
2 .The genetic code for the FMR-1 gene usually contains a limited
repetition of CGG sequences. The normal range is 5-50 repeats.
NORMAL
Repeats
5
50
CGG
FMR-1 Gene
3. Some people have an expanded number of CGG repeats. When the

number of CGG repeats is between 50 and 200, the individual is a
premutation carrier of fragile X syndrome. Carriers are not usually
affected by fragile X syndrome, but they are at risk of having affected
children.
50
200
PREMUTATION
FMR-1 Gene
CGG
4. If the number of repeats exceeds 200, usually this disrupts the code and
prevents the production of the FMR protein. These individuals have
the full mutation and usually are affected by fragile X syndrome.
200+
FULL MUTATION
FMR-1 Gene
CGG
1 .For a child to inherit fragile X syndrome,

one parent must be a carrier
2 .Since fragile X syndrome is carried on the
X chromosome, both males and females
can be carriers and can inherit the
syndrome.
Male carrier
X(Fragile) Y
Female carrier
X(Fragile) X
3. A carrier father can only transmit the

gene to his daughters, since he
transmits only a Y chromosome to his
sons. All of his daughters will inherit the
gene, but only in the premutation state.
4. A carrier mother usually has one normal X and one

fragile X. Her sons and her daughters each have a 50%
chance of inheriting the gene. When transmitted through
the mother, the fragile X gene may be inherited in the
premutation phase or it may expand to the full mutation.
Carrier mother
X (fragile )
X
X
X X(Fragile)
Daughter with fragile x
Normal Daughter
X
X(Fragile) Y
Son with fragile x
Normal Son
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 onethird 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.
What is the genetic mechanism of fragile X syndrome?
It is named fragile X because the X chromosome of

affected individuals is prone to breakage at a fragile site
near the tip of the long arm of the X chromosome.
Interestingly, this is not the only example of a fragile
sitemore than 40 others have been found in the
human genome. The syndrome includes symptoms
affecting mood and physical characteristics of joints and
connective tissue for example, and the mental
impairment ranges from mild to severe. Despite diverse
symptoms, it is believed that a single gene is involved.
Sometimes, however, when these repeat sequences are
being copied during DNA replication, extra repeats are
accidentally added.
function of the FMR1 protein is not known, but scientists have

hypothesized that it may be involved in transporting RNA and/or
proteins from the nucleus to the cytoplasm. The FMR1 protein is
found at high concentrations in neuronal cells, which might relate to
the mental impairment observed in affected individuals.
Diagnosis:
Any child with signs of developmental delay of speech, language, or
motor development with no known cause should be considered for
fragile X testing, especially if there is a family history of the condition.
Behavioral and developmental problems may indicate fragile X
syndrome, particularly if there is a family history of mental retardation.
Definitive identification of the fragile X syndrome is made by means of
a genetic test to assess the number of CGG sequence repeats in the
FMR-1 gene. Individuals with the premutation or full mutation may
be identified through genetic testing. Genetic testing for the fragile X
mutation can be done on the developing baby before birth through
amniocentesis or chorionic villus sampling (CVS), and is 99% effective
in detecting the condition due to trinucleotide repeat expansion.
Prenatal testing should only be undertaken after the fragile X carrier
status of the parents has been confirmed and the couple has been
counseled regarding the risks of recurrence. While prenatal testing is
possible to do with CVS, the results can be difficult to interpret and
additional testing may be required.
TREATMENT:
Presently there is no cure for fragile X syndrome.

Management includes such approaches as speech therapy,
occupational therapy, and physical therapy. The expertise of
psychologists, special education teachers, and genetic
counselors may also be beneficial. Drugs may be used to
treat hyperactivity, seizures, and other problems.
Establishing a regular routine, avoiding over-stimulation,
and using calming techniques may also help in the
management of behavioral problems. Children with a
troubled heart valve may need to see a heart specialist and
take medications before surgery or dental procedures.
Children with frequent ear and sinus infections may need to
take medications or have special tubes placed in their ears to
drain excess fluid. Mainstreaming of children with fragile X
syndrome into regular classrooms is encouraged because
they do well imitating behavior. Peer tutoring and positive
reinforcement are also encouraged.
The End

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ANN MARY TONY

What is FRAGILE X SYNDROME?

Fragile X syndrome is the most common form of

The mutation involves an expansion in a region of

FRAGILE X SYNDROME - A Single Gene Disorder

In the FMR-1 gene located on the EDX chromosome , most individuals

1. The FMR-1 gene is located on the X chromosome.

3. Some people have an expanded number of CGG repeats. When the

1 .For a child to inherit fragile X syndrome,

3. A carrier father can only transmit the

4. A carrier mother usually has one normal X and one

Daughter with fragile x

What Are the Common Symptoms of

mental impairment, ranging from learning

Boys are typically more severely affected than girls.

What is the genetic mechanism of fragile X syndrome?

It is named fragile X because the X chromosome of

function of the FMR1 protein is not known, but scientists have

Presently there is no cure for fragile X syndrome.

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