Fragile What? – An Overview of Fragile X Syndrome and its Associated Disorders

1. Fragile What? –An Overview of Fragile X Syndrome and its Associated Disorders Matt RhodesParent Contact - LINKS LeaderFragile X Association of Alabama

2. Fragile X Associated Disorders FXS – Fragile X Syndrome FXTAS – Fragile X-Associated Tremor Ataxia Syndrome FXPOI – Fragile X-Associated Primary Ovarian Insufficiency

3. FXS DEFINITION

4. Fragile X Syndrome • The world’s leading cause of inherited mental impairment • Symptoms ranging from learning problems to mental impairment and autism • Can be accurately diagnosed with a simple blood test or DNA

5. INCIDENCE

6. Prevalence • Affects 1 in 3,600 males & 1 in 4,000- 6,000 females • 1 in 260 women are carriers • 1 in 800 men are carriers • Fragile X appears in all socioeconomic background • In Alabama, carriers and full mutations are estimated at 15,978

7. Second only to Down’s Syndrome as a genetic cause of mental retardation • Unlike Down’s Syndrome, maternal age is not a factor

8. 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

9. GENETICS

10. SCAN in page 14

11. Parents – X’s and Y’s Father Mother Father Mother X Y XX X Y XX Son Daughter XY XX

12. Woman with a premutation on one of her two X chromosomes Her egg cells Egg cell without a fragile X mutation Egg cell with a fragile X mutation Plus father’s X Plus father’s X Plus father’s Y Plus father’s Y Girl with out fragile X mutation Girl with fragile X mutation Boy with out fragile X mutation Boy with fragile X mutation

13. Man with a premutation on his one X chromosome His sperm cells Sperm cell without a Y sex chromosome Sperm cell with a fragile X mutation Plus Mother’s X Plus Mother’s X Boy with out fragile X mutation Girl with premutated carrier

14. BOYS 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 GIRLS Approximately 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 Both Males and Females Can Have Fragile X Syndrome

15. Direct DNA Analysis for the Fragile X Mutation

16. 1 2 3 4 5 6 Father XY Mother XX CGG Repeats INCREASING Pre-mutated Male XY Pre-mutated Female XX Unaffected Female XX XY XY XX XY Unaffected Unaffected Unaffected XY XX XX X – Pre-mutation X – Full Mutation XX XX

17. CLINICAL FEATURES

18. Physical Characteristics • Large ears • Long, narrow face • Prominent forehead • Prominent, square chin • High palate (roof of mouth) • Hand calluses • Mitral valve prolapse (a leaky heart valve) • Seizures • Eye problems

19. Physical Characteristics Often Seen in Young Children: • Numerous ear infections • Flat feet • Hyper extensible joints • Eye problems in 20%-25%: • Refractive errors • Strabismus • Astigmatisms • Seizures • Missing developmental milestones

20. Common Difficulties • Sleeping • Toilet training • Socialization • Play (spinning objects, play with exclusive toy, or part of toy)

21. Cognitive • The Fragile X mutation affects brain development and leads to a range of cognitive delays. • Developmental delays • Mental impairment • Learning disabilities

22. Difficulties with frontal lobe functions(“executive” functions) • Organization of information • Acting on that information in an effective manner • Focusing attention • Forming a plan and carrying it out

23. Behavior • Attention deficits • Hyperactivity • Impulsivity • Autistic-like behaviors • Repetitive behaviors • Hand flapping • Hand biting • Gaze aversion • Extreme anxiety, shyness • Transition problems, difficulty adjusting to change

24. Cognitive/ Behavioral Strengths • Strong visual memory • Long term memory • Good verbal imitative skills • Desire to be social • Strong appreciation of humor • Often receptive to helping or working cooperatively

25. Speech and Language Characteristics • Delayed speech • Problems with intelligibility • Rapid, repetitive speech (perseveration) • Echolalia • Poor conversation skills • Good verbal imitative skills

26. Sensory Processing Characteristics • Tactile defensiveness • Visual defensiveness • Olfactory defensiveness • Oral defensiveness • Gravitational/ postural insecurity

27. Sensory processing often seen in infants and young children • Excessive mouthing and drooling • Mouth stuffing • “picky” eaters • Difficult to calm and comfort • Over sensitivity to sounds

28. Gross Motor Characteristics • Low muscle tone • Delays in gross motor skills • Uncoordinated, clumsy

29. Fine Motor Characteristics • Low muscle tone • Hyper extensible finger joints • Difficulties with fine motor joints • Self feeding • Dressing • handwriting

30. Characteristics Often Seen in Females With FX • Attention deficits • Shyness and anxiety • Selective mutism • Problems with math • Increased risk for mental health issues such as depression, bipolar disorder, and obsessive compulsive disorder • 25% premature ovarian failure (early menopause)

31. INTERVENTIONS

32. Early/ Preschool Interventions • Speech and language therapy • Occupational therapy • Occasional physical therapy • Settings with consistency, structure and routine • Total communication program • Simultaneous not sequential • Visual learners • Incidental learners

33. 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

34. Managing Hyperarousal Nervous system over stimulated Evokes fear/flight responses Anxiety can lead to hyperarousal Use calming, coping and comfort to help self-regulation Manage environment

35. Reducing Anxiety Beginning and ending clearly defined Picture schedules Calm environment Maintaining schedule

36. 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

37. 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

38. Middle/ High School Interventions • Continue therapies if appropriate • Relevant and functional reading and learning experiences • Social skills training • Introduce pre-vocational opportunities • Recreational/ extracurricular • (Special Olympics, choirs, other musical venues)

39. Adult Opportunities • Employment • Independent living options • Socialization and adult relationships • Recreation

40. Trampolines Bicycling Swimming Bowling Soccer Gym/Fitness Center Softball Martial Arts Scouts Choirs or other musical venues Special Olympics Challenger sports Suggested Recreational Opportunities

41. Attention-related problems Hyperactivity/ impulsivity Mood disorders/ depression Anxiety/ panic Aggression Obsessive/ compulsive symptoms Bedwetting Sleep disorders Seizures Self injury Medications

42. FXTAS Symptoms and Diagnosis • FXTAS 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 declineThe 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.

43. FXPOI • 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

44. 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 .

45. Fragile X Research & Clinic Consortium

46. Linking Individuals in Knowledge and Support

47. Fragile X Advocacy Day March 3, 2010 in Washington, D.C.

48. The National Fragile X Foundation P.O. Box 190488 San Francisco, CA 94119-0048 800-688-8765 www.FragileX.org Email: NATLFX@FragileX.org

49. Fragile X Association of Alabama • Matt Rhodes • 2710 Wellington Circle • Pelham, AL 35124 • www.fxalabma.org • Email: mattr@fxalabama.org

50. The National Fragile X Foundation Serving the Fragile X community since 1984