fragile x syndrome and inheritance

1. FRAGILE X
SYNDROME
By: A.G.M

2. Fragile x syndrome(FXS) is a genetic disorder that is characterized
from mild-severe intellectual disability. It is also one of the
leading cause of autism.
It is a syndrome that is closely associated with the gene FMR1
that results in intellectual disabilities as well as affecting the
physical features of a person.
What is the FMR1 gene?
The FMR1 gene is a human gene that provides instructions for
making a protein called FMRP. This protein is present in many
tissues, including the brain, testes, and ovaries. In the brain, it may
play a role in the development of connections between nerve cells
(synapses), where cell-to-cell communication occurs. It is located
on the X chromosome and contains a repeated CGG trinucleotide.

3. CAUSE
It is caused by a change in the FRM1 gene.
Children with fragile X syndrome usually have mutations involving an expansion of the CGG
nucleotide repeat region in the 5’ untranslated region of the fragile-X Mental Retardation-1
(FMR1) gene. In this case, the appearance of this portion of the chromosome X is dangling
by a thread.
FRMR1 gene on the X chromosome makes a protein called FRMP(fragile x mental
retardation protein). FRMP protein is required for normal neural development.
The repetition of the CCG nucleotide varies in FRM1 gene:
Range of repetition of CCG Risk of having FXS
5-44 Normal
45-54 Intermediate
55-200 Pre-mutation
>200 Full mutation

7. FRAGILE X SYNDROME
INHERITANCE
 Fragile X syndrome is inherited in an X-linked dominant pattern. The inheritance is
dominant if one copy of the altered gene in each cell is sufficient to cause the
condition. X-linked dominant means that in females (who have two X
chromosomes), a mutation in one of the two copies of a gene in each cell is
sufficient to cause the disorder. In males (who have only one X chromosome), a
mutation in the only copy of a gene in each cell causes the disorder. In most cases,
males experience more severe symptoms of the disorder than females.
It affects 1 in 4000 males and 1 in 8000 females of all race and ethnic groups.Boys
with fragile X are usually diagnosed by age 3. Since girls tend to have milder
symptoms, they are often not diagnosed until later.
It is easier for the male gender to have the FXS because they have they XY
chromosome( only one X) and the females are more common carriers of FXS since
there two X chromosomes (XX).

9. PHYSICAL AND
COGNITIVE
FEATURES OF FXS
• Prominent long ears
• Soft fleshy skin
• Flat feet
• Ear infections
• A long face and broad forehead
• Strabismus (crossed eyes)
• Delayed and repetitive speech
• Hyperactivity and oversensitivity
• Autistic-like behaviors
• Large testes
• Tactile defensiveness
• Gross motor delays
• Seizures in 20%

10. DIAGNOSIS AND TREATMENT
The diagnosis of fragile x syndrome is confirmed by the molecular genetic testing to
determine the number of CCG repeats in the FRM1 gene. This type of testing is also
offered to individuals/patients who have a family history of a genetic disorder.
Early detection of Fragile X is important as this allows for early intervention and
management with medication, specialized education and behavioral therapy, which
maximizes learning potential of each child. There is no specific treatment for Fragile
X syndrome and individuals with this syndrome undergo different types of
therapies(speech-language therapy, occupational therapy, physical therapy and
behavioral therapy).
PREVENTION: Genetic counselling for couples who have a family background of this
syndrome and want to have children.

12. REFERENCES
www.google.com/search?q=fragile+x+syndrome+diagnosis&rlz=1C1CHBF
_enGE850GE850&oq=fragile+x+syndrome+diagn&aqs=chrome.0.0j69i57j0j
46j0j69i60l3.7642j0j7&sourceid=chrome&ie=UTF-8
www.google.com/search?q=fragile+x+syndrome+inheritance&rlz=1C1CHB
F_enGE850GE850&oq=fragile+x+syndrome+i&aqs=chrome.1.69i57j0l4j69i
60l3.5902j0j7&sourceid=chrome&ie=UTF-8
https://ghr.nlm.nih.gov/condition/fragile-x-syndrome#inheritance
www.google.com/search?q=fragile+x+syndrome+associated+disorders&rl
z=1C1CHBF_enGE850GE850&oq=fragile+x+syndrome+ass&aqs=chrome.3.
69i57j0l7.8576j0j7&sourceid=chrome&ie=UTF-8
www.researchgate.net/publication/12549862_Understanding_the_molecula
r_basis_of_fragile_X_syndrome_Hum