Why Fragile X syndrome
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Transcript of Why Fragile X syndrome
Why Study Fragile X
By Dr Shewikar El Bakry
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
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/
Clinical Picture• Intellectual• Physical• Behavioural and emotional• Feeding• Speech and language• Sensory
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
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
(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
Adult onset Premutation: common is general population
Males: 1:813Females: 1:259
1/3 of male premutation population develop FXTAS
Fragile X associated Tremor and Ataxia Syndrome
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
Early/ Preschool Interventions
• 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
Elementary School Interventions
– 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
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
THANK YOU
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