FXS
Fragile X Genotype & Phenotype • Phenotype = The observable manifestations of a person’s genotype (which includes physical Syndrome characteristics su ch as height & facial featu res, as well as predisposition to certain health problems: heart disease, strabismus). Terry Broda • Genotype = A person ’s genetic makeup (the RN[EC], BScN, NP-PHC, CDDN combination of genes of an organism or an individual). Dykens, Hodapp & Finucane, 2000
Chromosomes Chromosomes
• 46 chromosomes organised • 22 of the 23 pairs of in 23 pairs. chromosomes are similar in • These chromosomes both sexes & are called contain condensed coils of autosomes. DNA code in the form of • The chromosomes making genes. up the 23rd pair are called • One member of each the sex chromosomes chromosome pair is because they determine a inherited from your father & person’s gender. the other from your mother, at conception.
What exactly is a genetic Chromosomal Abnormalities • Most common type= mutation? ANEUPLOIDY = an • When one or both copies of a specific gene presents abnormal number of an alterati on i n th e DNA , w hic h a lters the des igna te d chromosomes (+ or -). function of that gene. – Monosomy (rare; ex. • For example, Turner syndrome(45X0). – Deletion or microdeletion of part of a – Trisomy (ex. Down (21), 13, 18, Klinefelter chromosome. (XXY)) – Repetition of genetic code: CGG
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Fragile –X Syndrome
• Section q27.3 of the χ chromosome Fragile –X Syndrome • Most common inherited cause of DD • Prevalence: • Females usually have milder symptoms – 1 / 1500-4000males (compensation by other X chromosome) – 1 / 2500-8000 females • Often initial dx of autism or PDD-NOS – 1 / 256 females are • 39% of males with fragile χ had dx of autism or PDD in carriers of the childhood premutation • 16-17% of adults with fragile χ meet DSM criteria for autism (Rousseau et al., 1995) • 0-16% males with dx of autism test + for fragile χ – 1/800 males are carriers
• Present in all ethnic groups
Fragile X Syndrome *FXTAS: Fragile X-associated • Fragile X syndrome is associated with an expanded Tremor/Ataxia Syndrome repetition of the trinucleotide CGG which, in « normal » persons, is repeated between 6 and 50 • Progressive neurological disorder: times. – tremor & ataxia (& eventually memory problems, moodiness & irritability) 1) normal = 6 - 50 CGG repeats • Onset 50-60yrs (granddads of Fragile X kids) 2) premutation = 50-200 CGG repeats (*FXTAS) • ONLY 20-30% of male carriers >50 affected 3) full mutation = 200 + CGG repeats (Fragile X) • Often misdx’ed as atypical Parkinson’s, multiple system *increased impact over generations atrophy, etc • May provide insight into FMR1 gene deactivation
Characteristic features: Characteristic features: • Associated medical concerns: • Long face • Prominent chin – Strabismus - Serous otitis • Prominent ears – Flat feet -Dislocated hips • Larger head circumference – Mitral valve prolapse - GERD • Joint hypermobility/hyperextension (MVP) - ADHD • Macro-orchidism – Obs Sleep apnea - Seizures (OSA) - Mental retardation – Autistic features (poor eye contact, hand-flapping, hand-biting)
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Shyness, social anxiety & Sensory Issues: • hyper arousal (sound of fluorescent lights, sight of too many hypersensitivity decorations on wall) • hypo arousal (sound of the teacher's voice, rather than the sound • Shy, timid personality of the humminggp, computer, fluorescent li g,qghts, and aquarium bubbler ) • sensory motor integration problems (including motor • Difficulties w/ peer interactions planning issues and fine motor weaknesses) compared to interactions w/ adults. • tactile defensiveness (hypersensitivity to touch) • Excessive anxiety in new • difficulty in many new, confusing, or loud situations situations/environments. (because of a combination of sensory integration problems, anxiety, • Hypersensitivity: Tendancy to ‘overreact’ and attention deficit disorders) to ‘minor’ frustrations .
Tactile Defensiveness Tactile Defensiveness • Affects 60-90% of FXS boys & some FXS girls • Firm, sure touches (handshakes & bearhugs) may be • Overreaction to touch & may avoid it tolerated better than light touch (tickling, soft touch of • Increased or decreased reactions to textures: face) – Clothing & tags • May prefer to be at end of the line, separate from crowd – Need soft fabrics, no elastic cuffs or hems • Infants may/may not be comforted by cuddling – May prefer deep pressure of heavy clothing for increased • May not enjoy finger painting or other tactile art activities feedback • Have difficulty identifying objects or feeling & receiving info by touch
Tactile Defensiveness Remember: • Difficulties with hygiene: – Bathing, face & hair washing, shaving, nail cutting • Dental visits may be difficult & anxiety provoking • A specific problem in the environment that can be • Difficu lties w ith eating: modified will often effect a much larger improvement – Difficulty nursing from breast or bottle in behavior than medication! – Strong food preferences related to textures of food • Maximize environment FIRST to get a reasonable – Mouth stuffing of mouth, due to high “cathedral” palate, before baseline! realizing they may gag
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Tactile Defensiveness: Tactile Defensiveness: strategies for intervention strategies for intervention • Sensory diet: individualized by an OT • Calming activities: • Uses neurodevelopmental therapy working with muscle – Rocking, swinging child tone & sensory integration therapy (SI), involving all senses – Applying deep pressure plus proprioreception (body position in space) & vestibular – Brushing child’s skin with therapeutic brush (sense of gravity & motion) input – Break time: quieter area, playing computer game or listening • To find best combination & timing of various sensory inputs to music or a story on headphones & decreases sensory overload
Tactile Defensiveness: Fine & Gross Motor skills strategies for intervention • Movement therapy to improve balance, muscle tone & proprioception: • Environmental changes: – dan ce, m arti al art s, sport s, ph ysi cal pl ay – ItllihtIncrease natural light – Limit/avoid exposure to loud situations • Practice to improve use of – Gradual desensitization to be able to tolerate more noise – pens/pencils for writing & drawing – Adapted seating to help maintain upright posture with enough – utensils, scissors & tools feedback: – Keyboard (computer use) • Donut-shaped cushions, foam wedges
Fragile X Syndrome - Oral-motor activities attention deficits/hyperactivity • Activities to • ª distractions: study cubicles, desk at front of – increase tolerance to touch around face & mouth classroom or in calm area (facing a wall), periods of – improve chewing, swallowing & speaking quiet time, decreased flow of traffic in room, adequate • Use of foods & toys: natural lighting & heat, small group instruction, reduced – Blow toys, whistles, straws noise level – Crunchy or chewy food: fruit snacks, celery, bagels, gum • Seating near an exit, allow removal from stressful – *may decrease chewing on clothing, straps or skin! events • © use of visual cues (photos, etc) for transitions • Provide non-verbal cues & feedback • Simple phrases & concrete communication • Structure/routine/predictability
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FXS - more teaching Fragile X Syndrome - approaches… general approach • Using pictograms, photos, objects of special interest or • Do not force eye contact! (gaze aversion) hands-on approach • BflidilBe careful invading personal space &thith& touching the • Us ing c loc ks, license p la tes & coo king to he lp w ith person! (tactile sensitivity) number concepts • Consistency important! (staffing, schedules, • Indirect explanation: teach task to neighbour environment) • Apply person’s strengths: long-term memory, imitation • *Provide a book to carry with them containing info skills, sense of humour that may be difficult to remember • Teach complete tasks: present whole process (not step- by-step) & use cover up method to follow sequence (Ø lose his place)
FXS – ADL stuff FXS – ADL stuff • Sleep: • Dressing: – Remove tags, soft fabrics – PJs & bedding – Buttons, snaps easier or T-shirts – Dark room/shades – Shoes w/ velcro, curly laces – Soothing sounds, music – Bedtime routine • Hygiene: • Eating: – Desensitization to water on skin, calming strategies – Pictures of sequence of activities – Try various nipples/positions – Firm pressure with facecloth vs light strokes – OT interventions for improved oral motor functioning • Dental – Egg timer – Desensitization: books, visits w/ mom, sibling
FXS - strategies vs. aggression FXS - strategies vs. aggression • Functional analysis: A-B-C data collection • Indications of anxiety: •Aggression ma y be preceded b y gi gglin g, – Worry/anxiety over changes in routine or non-compliance or avoidance upcoming stressful events (fire drills, assemblies): • Most common cause: anxiety! ‘hyper vigilance’ • May be d/t sensory processing problems or – Will stiffen up when angry or upset, becoming rigid hypersensitivity: sensory stimulation ‘adds up’ during the & tense day & sensory activities may be more challenging later in – May simply tighten up hands the day ( © demands are more difficult) – Crying, whining tantrums may all be d/t • *higher incidence in adolescents: hormones! overwhelming settings!
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FXS - strategies vs. Fragile X Syndrome - aggression strategies vs. aggression • “Catch them being good!” with reinforcement of + • Relaxation training, sensory stimulation/ sensory behavior itintegrati on (OT) , musi c • Specific interventional approaches: ABA, Lovaas, token • Deep pressure massage economy, ‘time-outs’ (removal of attention) • Use of imagery • Psychotherapy & individual counselling (self-esteem, • Group Therapy & Social Skills training (role playing, depression, anxiety, coping skills, frustration, anger especially with behavioral consequences) management, social skills) • Family Therapy
*Fragile X Syndrome - FXS - strategies vs. aggression issues around sexuality Consider differentials: • Social Sexual skills 1. Panic episodes: ‘fight or flight’: flushing, turning pale, rapid • SEdthht&bdbtSex Ed. throughout & beyond puberty breathing, sudden sweating • Sexual abuse prevention information 2. Mood disorders: Depression or Bipolar disorder • Psychotherapy & counselling (self-esteem, depression, (disturbed or absent sleep, excess or loss of appetite, changes in anxiety/frustration) (especially helpful for transition activity level, mood changes, increased irritability) from parents’ home to independent living) 3. Seizure disorder (aggression appears aimless, or unassociated with any ongoing event, occurring with unusual movements, brief loss of consciousness, confusion or need to sleep afterwards)
Websites
Treatment • Geneclinics : http://geneclinics.org/ (see: Gene Reviews)
• Referrals to : speech Tx, OT, behavioural Tx • Your Genes, Your Health: http://www.ygyh.org/ • • Medications for medical problems: epilepsy , MVP & HTN • OliOnline M end dlielian IhInher itance in • Medications for psychiatric problems: anxiety (anti-anxiety: Man: http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=OMIM SSRIs) & ADHD • • Genetics Education Center, University of Kansas Medical • Future prospects: gene therapy Center: http://www.kumc.edu/gec/support/ • • The Family Village: http://www.familyvillage.wisc.edu •
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Websites Websites Health Watch tables for several genetic syndromes & other tools from the Canadian Consensus Guidelines developed at Surrey Place in Ontario, Canada: Genetics Website www.surreyplace.on.ca/Clinical-Programs/Medical- Services/Pages/PrimaryCare.aspx (In English, French, Spanish, German, Italian & Portuguese!): • The Fragile X Research Foundation of Canada • Orphanet: http://www.orpha.net/consor/cgi-bin/index.php Website: http://www.fragile-x.ca • FRAXA Research Foundation (USA) Website: www.fraxa.org • The National Fragile X Foundation (USA) Website: http://www.nfxf.org/html/what.htm or http://www.fragilex.org/html/home.shtml
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