why fragile x syndrome
DESCRIPTION
TRANSCRIPT
![Page 1: Why Fragile X syndrome](https://reader033.vdocument.in/reader033/viewer/2022061116/5465c591af795997368b4f08/html5/thumbnails/1.jpg)
Why Study Fragile X
By Dr Shewikar El Bakry
![Page 2: Why Fragile X syndrome](https://reader033.vdocument.in/reader033/viewer/2022061116/5465c591af795997368b4f08/html5/thumbnails/2.jpg)
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
![Page 3: Why Fragile X syndrome](https://reader033.vdocument.in/reader033/viewer/2022061116/5465c591af795997368b4f08/html5/thumbnails/3.jpg)
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/
![Page 4: Why Fragile X syndrome](https://reader033.vdocument.in/reader033/viewer/2022061116/5465c591af795997368b4f08/html5/thumbnails/4.jpg)
![Page 5: Why Fragile X syndrome](https://reader033.vdocument.in/reader033/viewer/2022061116/5465c591af795997368b4f08/html5/thumbnails/5.jpg)
Clinical Picture• Intellectual• Physical• Behavioural and emotional• Feeding• Speech and language• Sensory
![Page 6: Why Fragile X syndrome](https://reader033.vdocument.in/reader033/viewer/2022061116/5465c591af795997368b4f08/html5/thumbnails/6.jpg)
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
![Page 7: Why Fragile X syndrome](https://reader033.vdocument.in/reader033/viewer/2022061116/5465c591af795997368b4f08/html5/thumbnails/7.jpg)
![Page 8: Why Fragile X syndrome](https://reader033.vdocument.in/reader033/viewer/2022061116/5465c591af795997368b4f08/html5/thumbnails/8.jpg)
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
![Page 9: Why Fragile X syndrome](https://reader033.vdocument.in/reader033/viewer/2022061116/5465c591af795997368b4f08/html5/thumbnails/9.jpg)
(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
![Page 10: Why Fragile X syndrome](https://reader033.vdocument.in/reader033/viewer/2022061116/5465c591af795997368b4f08/html5/thumbnails/10.jpg)
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
![Page 11: Why Fragile X syndrome](https://reader033.vdocument.in/reader033/viewer/2022061116/5465c591af795997368b4f08/html5/thumbnails/11.jpg)
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
![Page 12: Why Fragile X syndrome](https://reader033.vdocument.in/reader033/viewer/2022061116/5465c591af795997368b4f08/html5/thumbnails/12.jpg)
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
![Page 13: Why Fragile X syndrome](https://reader033.vdocument.in/reader033/viewer/2022061116/5465c591af795997368b4f08/html5/thumbnails/13.jpg)
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
![Page 14: Why Fragile X syndrome](https://reader033.vdocument.in/reader033/viewer/2022061116/5465c591af795997368b4f08/html5/thumbnails/14.jpg)
THANK YOU
QUESTIONS