1. Why Study Fragile X
By Dr Shewikar El Bakry

2. What??
• Fragile X syndrome =genetic condition +typical physical
attributes(phenotype) +behavioural + developmental.
• Most common form inherited MR.
• The specific gene(FMR1) on the X chromosome makes a
protein necessary for brain development.
• FMR1
DNA segment(CGG triplet repeat)
up to
200
inactivate gene
prevent protein
s&s
• Constriction Band

3. Fragile X Syndrome (FXS)
•
expansion of CGG which affects
the FMR1 (fragile X mental
retardation 1 gene)
• 200 or more CGG repeats
• this leads to a failure to express
FMRP (fragile X mental retardation
protein)
• FMRP is needed for normal
neural development
• absence of FMRP leads to
abnormalities in brain
development and function
http://cibar.stanford.edu/fragx/

5. Clinical Picture
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Intellectual
Physical
Behavioural and emotional
Feeding
Speech and language
Sensory

6. Prevalence
• 1 in 3,600 males
• 1 in 6,000- 8,000 females
• 1 in 260 women are carriers
• 1 in 800 men are carriers
• All socioeconomic background
• All ethnic groups
• Second to Down’s Syndrome as a genetic cause of MR
• About 30% of individuals with Fragile X Syndrome have
autism
• 2-6% of individuals with autism have Fragile X Syndrome

8. Diagnosis
• both a standard karyotype and DNA testing are suggested
when a possible diagnosis of fragile X syndrome is considered.
• detect the FMR1 gene. The exact number of CGG triplet
repeats can be determined

9. (FXTAS)
Fragile X associated Tremor and Ataxia Syndrome
Adult onset
Premutation: common is
general population
Males: 1:813
Females: 1:259
1/3 of male premutation
population develop FXTAS
• late-onset, progressive cerebellar
ataxia and intention tremor in males
who have a premutation.
• Other neurologic findings include
short-term memory loss, executive
function deficits, cognitive decline,
parkinsonism, peripheral
neuropathy, lower-limb proximal
muscle weakness, and autonomic
dysfunction

10. FXPOI
• Fragile X-Associated Primary Ovarian Insufficiency
• Affects female pre-mutation carriers (55-200 CGG
repeats)
• Female with the full mutation do not appear to be at
risk
• FXPOI causes decreased ovarian function
• 23% experience early menopause (prior to age
40)
• 20-28% experience ovarian insufficiency
• many experience decreased fertility

11. Early/ Preschool Interventions
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Speech and language therapy
Occupational therapy
Occasional physical therapy
Settings with consistency, structure and routine
Total communication program
Visual learners
Use calming, coping and comfort to help self-regulation
Manage environment

12. Elementary School Interventions
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Speech therapy
Occupational therapy
Extracurricular (sports, scouts, dance, martial arts)
Full inclusion with support
Mainstreaming
Self-contained programs
Predictable routines, rules and expectations
Consistent physical layout of classroom
Minimize auditory distractions
Picture schedule
Augmentative communication
computers

13. Essential update:
• Clinical improvement with minocycline documented in fragile X
syndrome
• In a randomized crossover study of 66 children ages 3.5 to 16 years of age
with fragile X syndrome, 3 months of treatment with the antibiotic
minocycline
• greater improvements in general behavior, anxiety, and mood-related
behaviors compared with placebo.
• Outcome measures including the Clinical Global Impressions-Improvement
(CGI-I) scale, Visual Analogue Scale (VAS) for behaviors, and the Aberrant
Behavior Checklist (ABC) were administered at baseline, 3 months and 6
months.
• Other outcomes were not significantly better with minocycline, including
behavior problems and verbal functioning

14. QUESTIONS
THANK YOU