Why Fragile X syndrome

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Why Study Fragile X By Dr Shewikar El Bakry

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Transcript of Why Fragile X syndrome

Page 1: Why Fragile X syndrome

Why Study Fragile X

By Dr Shewikar El Bakry

Page 2: Why Fragile X syndrome

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

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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/

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Clinical Picture• Intellectual• Physical• Behavioural and emotional• Feeding• Speech and language• Sensory

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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

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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

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(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

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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

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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

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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

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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

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THANK YOU

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