2. DEFINITION
• A X-linked dominant disease caused by CGG
trinucleotide repeat expansion in the FMR1 gene
( fragile X mental retardation 1 gene) during oogenesis.
• This leads to its hypermethylation , which silences the
gene and renders it unable to express its physiological
gene product.
3. CAUSES OF FXS
• FMR1 gene on the X chromosome makes a protein called fragile x
mental retardation protein (FMRP)
• FMRP – protein required for normal neural development
• The Fragile X mutation results in an FMR1 gene that is switched off,
which means that FMRP is no longer produced , preventing normal
neuronal development
• FXS depends on repetition CGG in FMR1 gene where
4. EPIDEMIOLOGY
• Second most common genetic cause of intellectual disability (after
trisomy 21)
• Most common inherited cause of intellectual disability ( after trisomy
21)
• INHERITANCE : Males are more frequently affected than females
5. PHYSICAL CHARACTERISTIC
• Large testes (Macroorchidism)
• Large ears
• Long, narrow face
• Soft skin
• Poor eyesight
• Large body size
• Square chin
• Frontal bossing
CLINICAL MANIFESTATIONS
The clinical presentation varies depending on the number
of trinucleotide repeats.
50 – 200 repeats ( premutation) : ataxia , primary ovarian
insufficiency , tremor
>200 repeats ( full mutation) :
6. SPEECH & LANGUAGE CHARACTERISTIC
• Delayed speech
• Rapid repetitive speech
• Poor conversation skills
• Good verbal imitative skills
CONGINITIVE (LEARNING & UNDERSTANDING)
• Developmental delays
• Mental Retarded
• Learning disabilities
•Hypermobile joints
•Mitral valve prolapse : can lead to mitral regurgitation
•Focal seizures
BEHAVIORAL FEATURES
• Austistic behavior
• Hyperactivity
• Anxiety
8. Boy of primary
school age with a
long and narrow face
and large ears. Both
features are typical
in children with
fragile X syndrome.
9. COMMON DIFFICULTIES
• Sleeping
• Mouth stuffing
• “picky” eaters
• Socialization
• Toilet training
• Over sensitivity to sounds
• Difficult to calm and comfort
• Excessive mouthing and drooling
• Playful (spinning objects, play with
exclusive toy, or part of toy)
MEDICAL CONCERNS
• Ear infections
• Eye problems
Strabismus (inability to focus both
eyes on an object)
Hyperopia (far-sightedness)
• High blood pressure (can be treated
with medication)
10. Diagnosis
Molecular Genetic testing
(PCR , Southern blot)
Cytogenic detection (not very
senstitive)
Echocardiography ( to exclude
mitral valve proplase)
• Diagnosis of FXS is made through genetic
testing to determine the number of CGG
repeats in FMR1 (carrier testing)
Carrier testing: Carrier testing is used to identify
who carry a copy of gene mutation or in two
copies, causes a genetic disorder. This type of
testing is offered to individuals who have a
family history of a genetic disorder.
11. • There is NO SPECIFIC TREATMENT for FXS
• Therapy Treatments
Speech-language therapists - improve their pronunciation of words and sentences, slow
down their speech, and use language more effectively.
Occupational therapists - help find ways to adjust tasks and conditions to match a
person’s needs and abilities.
Physical therapists - design activities and exercises that help build motor control and
improve posture and balance.
Behavioural therapists try to understand why someone with Fragile X acts out, and they
create ways and strategies for avoiding or preventing these situations from occurring
while also teaching better or more positive ways to respond to situations.
• However they are some symptoms that can be controlled by a medication such as
attention deficit, hyperactivity, anxiety, and aggression.
TREATMENT
