Fragile What? –
An Overview of Fragile X
Syndrome and its Associated
Disorders
Matt Rhodes
Parent Contact - LINKS Leader
Fragile X Association of Alabama
Fragile X
Associated Disorders
FXS –
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 impairment
Symptoms ranging from learning
problems to mental impairment
and autism
Can be accurately diagnosed with
a simple blood test or DNA
INCIDENCE
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
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
Parents – X’s and Y’s
Father
Mother
Father
Mother
XY
XX
XY
XX
Son
Daughter
XY
XX
Woman with a premutation
on one of her two X chromosomes
Her egg cells
Egg cell
without
a fragile X
mutation
Plus
father’s X
Egg cell
with
a fragile X
mutation
Plus
father’s Y
Plus
father’s X
Plus
father’s Y
Girl with out
fragile X
mutation
Boy with out
fragile X
mutation
Girl with
fragile X
mutation
Boy with
fragile X
mutation
Man with a premutation
on his one X chromosome
His sperm
cells
Sperm cell
without
a Y sex
chromosome
Plus
Mother’s X
Boy with out
fragile X
mutation
Sperm cell
with
a fragile X
mutation
Plus
Mother’s X
Girl with
premutated
carrier
Both Males and Females Can
Have Fragile X Syndrome
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
Direct DNA Analysis for the
Fragile X Mutation
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~55 to ~200
mutation
unmethylated
Usually
not
affected
Usually
not
affected
Full
>200
mutation
Completely methylated
~50%
affected
All
affected
Father
XY
1
2
3
Pre-mutated Female
XX
Pre-mutated Male
XY
XX
Mother
XX
XY
XY
Unaffected
Unaffected
XX
CGG
Repeats
Unaffected Female
XY
Unaffected
4
XY
XX
5
XX
XX
X – Pre-mutation
X – Full Mutation
6
XX
I
N
C
R
E
A
S
I
N
G
CLINICAL FEATURES
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
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
Common Difficulties
Sleeping
Toilet training
Socialization
Play (spinning objects, play with
exclusive toy, or part of toy)
Cognitive
The 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 information
Acting on that information in an
effective manner
Focusing attention
Forming a plan and carrying it out
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
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
Speech and Language
Characteristics
Delayed speech
Problems with intelligibility
Rapid, repetitive speech
(perseveration)
Echolalia
Poor conversation skills
Good verbal imitative skills
Sensory Processing
Characteristics
Tactile defensiveness
Visual defensiveness
Olfactory defensiveness
Oral defensiveness
Gravitational/ postural insecurity
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
Gross Motor Characteristics
Low muscle tone
Delays in gross motor skills
Uncoordinated, clumsy
Fine Motor Characteristics
Low muscle tone
Hyper extensible finger joints
Difficulties with fine motor joints
Self feeding
 Dressing
 handwriting

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)
INTERVENTIONS
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
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 stimulated
Evokes fear/flight responses
Anxiety can lead to hyperarousal
Use calming, coping and comfort
to help self-regulation
Manage environment
Reducing Anxiety
Beginning and ending clearly defined
Picture schedules
Calm environment
Maintaining 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 appropriate
Relevant and functional reading and
learning experiences
Social skills training
Introduce pre-vocational opportunities
Recreational/ extracurricular

(Special Olympics, choirs, other musical
venues)
Adult Opportunities
Employment
Independent living options
Socialization and adult
relationships
Recreation
Suggested Recreational
Opportunities
Trampolines
Bicycling
Swimming
Bowling
Soccer
Gym/Fitness
Center
Softball
Martial Arts
Scouts
Choirs or other
musical venues
Special Olympics
Challenger sports
Medications
Attention-related
problems
Hyperactivity/
impulsivity
Mood disorders/
depression
Anxiety/ panic
Aggression
Obsessive/
compulsive
symptoms
Bedwetting
Sleep disorders
Seizures
Self injury
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 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, and
3) Magnetic Resonance Imaging (MRI) findings that are known to be
related to FXTAS, including white matter changes or decreased size of the
brain.
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
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
Foundation
P.O. Box 190488
San Francisco, CA 94119-0048
800-688-8765
www.FragileX.org
Email: NATLFX@FragileX.org
Fragile X
Association of
Alabama
Matt Rhodes
2710 Wellington Circle
Pelham, AL 35124
www.fxalabma.org
Email: mattr@fxalabama.org
The National
Fragile X
Foundation
Serving the Fragile X community since 1984