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Fragile What? –An Overview of Fragile X Syndrome and its Associated Disorders
Matt RhodesParent Contact - LINKS LeaderFragile X Association of Alabama
Fragile X Associated DisordersFXS –
Fragile X Syndrome
FXTAS – Fragile X-Associated Tremor Ataxia Syndrome
FXPOI –Fragile X-Associated Primary Ovarian Insufficiency
FXS DEFINITION
Fragile X Syndrome
The world’s leading cause of inherited mental impairmentSymptoms ranging from learning problems to mental impairment and autismCan be accurately diagnosed with a simple blood test or DNA
INCIDENCE
PrevalenceAffects 1 in 3,600 males & 1 in 4,000- 6,000 females1 in 260 women are carriers1 in 800 men are carriersFragile X appears in all socioeconomic backgroundIn Alabama, carriers and full mutations are estimated at 15,978
Second only to Down’s Syndrome as a genetic cause of mental retardation
Unlike Down’s Syndrome, maternal age is not a factor
The most common known cause of autism
About 30% of individuals with Fragile X Syndrome have autism
2-6% of individuals with autism have Fragile X Syndrome
GENETICS
SCAN in page 14
X Y XX
Father Mother
X Y
Son
X Y XX
Father Mother
X X
Daughter
Parents – X’s and Y’s
Woman with a premutation on one of her two X chromosomes
Girl with out fragile X mutation
Girl with fragile X mutation
Plus father’s Y
Plus father’s Y
Plus father’s X Plus
father’s X
Egg cell without
a fragile X mutation
Egg cell with a fragile X mutation
Her egg cells
Boy with fragile X mutation
Boy with out fragile X mutation
Man with a premutation on his one X chromosome
Plus Mother’s X
Plus Mother’s X
Sperm cell without a Y sex
chromosome
Sperm cell with a fragile X mutation
His sperm cells
Boy with out fragile X mutation
Girl with premutated
carrier
Both Males and Females Can Have
Fragile X SyndromeBOYS
Approximately 85% of boys with F.M. have cognitive defects in the MR range (below 70)The production of FMR1 protein is usually shut down
GIRLSApproximately 70% of girls with F.M. have cognitive defects in borderline to M.R. range (below 70)Girls with more protein-producing cells tend to have higher IQs
Category
CGG repeats
Methylation of FMR1
Female
Male
Stable 6 to ~45 unmethylated Not affected
Not affected
Gray zone
~45 to ~55 unmethylated Not affected
Not affected
Pre-mutation
~55 to ~200 unmethylated Usually not affected
Usually not affected
Full mutation
>200 Completely methylated ~50% affected
All affected
Direct DNA Analysis for the Fragile X
Mutation
FatherXY
MotherXX
Pre-mutated MaleXY
Pre-mutated FemaleXX
Unaffected Female
XY XX XYXX XY
Unaffected Unaffected Unaffected
XY XX
XXXX
XX
1
2
3
4
5
6
CGGRepeats
INCREASINGX – Pre-mutation
X – Full Mutation
CLINICAL FEATURES
Physical Characteristics
Large earsLong, narrow faceProminent foreheadProminent, square chinHigh palate (roof of mouth)Hand callusesMitral valve prolapse (a leaky heart valve)SeizuresEye problems
Physical Characteristics Often
Seen in Young Children:Numerous ear infections
Flat feetHyper extensible jointsEye problems in 20%-25%: Refractive errors Strabismus Astigmatisms
Seizures Missing developmental milestones
Common Difficulties
SleepingToilet trainingSocializationPlay (spinning objects, play with exclusive toy, or part of toy)
CognitiveThe Fragile X mutation affects brain development and leads to a range of cognitive delays.
•Developmental delays
•Mental impairment
•Learning disabilities
Difficulties with frontal lobe functions
(“executive” functions)Organization of informationActing on that information in an effective mannerFocusing attentionForming a plan and carrying it out
BehaviorAttention deficits HyperactivityImpulsivityAutistic-like behaviors Repetitive behaviors Hand flapping Hand biting Gaze aversion
Extreme anxiety, shynessTransition problems, difficulty adjusting to change
Cognitive/ Behavioral Strengths
Strong visual memoryLong term memoryGood verbal imitative skillsDesire to be socialStrong appreciation of humorOften receptive to helping or working cooperatively
Speech and Language
CharacteristicsDelayed speech Problems with intelligibilityRapid, repetitive speech (perseveration)EcholaliaPoor conversation skillsGood verbal imitative skills
Sensory Processing Characteristics
Tactile defensivenessVisual defensivenessOlfactory defensivenessOral defensivenessGravitational/ postural insecurity
Sensory processing often seen in infants and young childrenExcessive mouthing and droolingMouth stuffing“picky” eatersDifficult to calm and comfortOver sensitivity to sounds
Gross Motor Characteristics
Low muscle toneDelays in gross motor skillsUncoordinated, clumsy
Fine Motor Characteristics
Low muscle toneHyper extensible finger jointsDifficulties with fine motor jointsSelf feeding Dressinghandwriting
Characteristics Often Seen in
Females With FXAttention deficitsShyness and anxietySelective mutismProblems with mathIncreased risk for mental health issues such as depression, bipolar disorder, and obsessive compulsive disorder25% premature ovarian failure (early menopause)
INTERVENTIONS
Early/ Preschool Interventions
Speech and language therapyOccupational therapyOccasional physical therapySettings with consistency, structure and routineTotal communication programSimultaneous not sequentialVisual learnersIncidental learners
Interventions Strategies
Sensory-based Strategies Sensory Diets Self-Regulation
Routines-based Strategies Maintain schedules Maintain routines Maintain Structure
Language-based Strategies Side Dialogues/Self Talk (Incidental Learning) Social Stories Video Modeling
Managing Hyperarousal
Nervous system over stimulatedEvokes fear/flight responsesAnxiety can lead to hyperarousalUse calming, coping and comfort to help self-regulationManage environment
Reducing AnxietyBeginning and ending clearly definedPicture schedulesCalm environmentMaintaining schedule
Elementary School Interventions
Intervention services Speech therapy Occupational therapy Extracurricular (sports, scouts, dance,
martial arts)
Classroom options Full inclusion with support Mainstreaming Self-contained programs
Structure Needs Predictable routines, rules and expectations Consistent physical layout of classroom Minimize auditory distractions
Teaching strategies Picture schedule Visual communications system (PECS) Augmentative communication computers
Middle/ High School Interventions
Continue therapies if appropriateRelevant and functional reading and learning experiencesSocial skills trainingIntroduce pre-vocational opportunitiesRecreational/ extracurricular (Special Olympics, choirs, other musical
venues)
Adult Opportunities
EmploymentIndependent living optionsSocialization and adult relationshipsRecreation
Suggested Recreational Opportunities
TrampolinesBicyclingSwimmingBowlingSoccerGym/Fitness Center
Softball Martial ArtsScoutsChoirs or other musical venuesSpecial OlympicsChallenger sports
MedicationsAttention-related problems Hyperactivity/ impulsivityMood disorders/ depressionAnxiety/ panicAggression
Obsessive/ compulsive symptomsBedwettingSleep disordersSeizuresSelf injury
FXTAS Symptoms and DiagnosisFXTAS usually develops between the ages of 50-80. Symptoms that family
members may notice, but often attribute to aging, include:
• "Intention" tremors -- shaking that often occurs when reaching for or pouring something
• Balance problems (ataxia) that cause falling or instability while walking
• Numbness in the extremities (neuropathy)
• Mood instability, irritability, and other changes in personality
• Short-term memory loss and gradual intellectual decline The diagnosis is based on 3 factors:1) Positive carrier testing for the FMR1 premutation,2) A neurological exam that affirms the above characteristics, and3) Magnetic Resonance Imaging (MRI) findings that are known to be related to FXTAS, including white matter changes or decreased size of the brain.
FXPOIFXPOI: 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 Symptoms and Diagnosis
• FXPOI causes decreased ovarian function
• 23% experience early menopause (prior to age 40)
• 20-28% experience ovarian insufficiency
• many experience decreased fertility
• many women with pre-mutations are able to conceive
• decreased ovarian function is detectable by blood tests that measure specific hormones, particularly FSH .
Fragile X Research &
Clinic Consortium
Linking Individuals in Knowledge and Support
Fragile X Advocacy Day
March 3, 2010 in Washington, D.C.
The National Fragile X
FoundationP.O. Box 190488
San Francisco, CA 94119-0048
800-688-8765
www.FragileX.org
Email: [email protected]
Fragile X Association of Alabama
Matt Rhodes
2710 Wellington Circle
Pelham, AL 35124
www.fxalabma.org
Email: [email protected]
The National Fragile X
Foundation
Serving the Fragile X community since 1984