Fragile X SyndromeFragile X Syndrome

Liz BickettLiz BickettTiffanie AlmeidaTiffanie Almeida

Michelle AcostaMichelle Acosta

Fragile X SyndromeFragile X Syndrome

Most common inherited form of Most common inherited form of mental retardationmental retardation

Fragile X can cause deficits in Fragile X can cause deficits in cognitive, behavioral, sensory, & cognitive, behavioral, sensory, & speech languagespeech language

PrevalencePrevalence MenMen

1 in 1,0001 in 1,000 1/5 show no obvious signs of the disorder1/5 show no obvious signs of the disorder

WomenWomen 1 in 2,0001 in 2,000 2/3 show no obvious signs of the disorder2/3 show no obvious signs of the disorder

(Sarason & Sarason, 1999)(Sarason & Sarason, 1999)

CharacteristicsCharacteristics

PhysicalPhysical Cognitive DevelopmentCognitive Development BehavioralBehavioral SensorySensory Speech and LanguageSpeech and Language

Physical CharacteristicsPhysical Characteristics Distinctive Facial FeaturesDistinctive Facial Features

Longer-than-usual faces and large earsLonger-than-usual faces and large ears

Connective Tissue ProblemsConnective Tissue Problems Double jointedness, ear infections, heart murmur, Double jointedness, ear infections, heart murmur,

and flat feetand flat feet

Enlarged Testicles (Males)Enlarged Testicles (Males) After puberty, nearly all will have testicles that are at After puberty, nearly all will have testicles that are at

least 2 times the volume of the typical maleleast 2 times the volume of the typical male

(The National Fragile X Foundation, 2006(The National Fragile X Foundation, 2006).).

Cognitive DevelopmentCognitive Developmentin Menin Men

Many have cognitive deficits, ranging from Many have cognitive deficits, ranging from mild to severemild to severe

Men who are only carriers generally have Men who are only carriers generally have normal intelligencenormal intelligence

Weaknesses are usually seen in higher Weaknesses are usually seen in higher order thinking and reasoning skills, as well order thinking and reasoning skills, as well as, quantitative skillsas, quantitative skills

Cognitive Strengths include verbal Cognitive Strengths include verbal reasoning and single word vocabulary, reasoning and single word vocabulary, along with high adaptive living skillsalong with high adaptive living skills

(The National Fragile X Foundation, 2006(The National Fragile X Foundation, 2006).).

Cognitive Development Cognitive Development in Womenin Women

Similar cognitive strengths and weaknesses as men Similar cognitive strengths and weaknesses as men with Fragile X but overall levels of performance are with Fragile X but overall levels of performance are generally higher.generally higher.

Approximately 30% of women with the full mutation Approximately 30% of women with the full mutation have IQ scores of 85 or above, although some of have IQ scores of 85 or above, although some of these women have specific learning disabilities. these women have specific learning disabilities.

Weaknesses are seen in "executive functioning“.Weaknesses are seen in "executive functioning“.

Strengths in females are generally found in Strengths in females are generally found in vocabulary and comprehension items on IQ tests.vocabulary and comprehension items on IQ tests.

(The National Fragile X Foundation, 2006(The National Fragile X Foundation, 2006).).

Behavior CharacteristicsBehavior Characteristics Children with Fragile X often have many behavioral Children with Fragile X often have many behavioral

challenges. These challenges are often one of the challenges. These challenges are often one of the main areas for identification of Fragile X.main areas for identification of Fragile X.

80-90% of boys identified are described as 80-90% of boys identified are described as distractible, with symptoms of ADHD. Girls have distractible, with symptoms of ADHD. Girls have less hyperactivity but still show symptoms of ADHD.less hyperactivity but still show symptoms of ADHD.

Many boys manifest behaviors such as hand Many boys manifest behaviors such as hand flapping, chewing on skin, clothing, or objects, flapping, chewing on skin, clothing, or objects, which may be connected to sensory problems and which may be connected to sensory problems and anxiety.anxiety.

Many behavior problems for both boys and girls Many behavior problems for both boys and girls overlap with the conversational difficulties they overlap with the conversational difficulties they have in language.have in language.

(The National Fragile X Foundation, 2006(The National Fragile X Foundation, 2006).).

Sensory ProblemsSensory Problems Parent’s of infants with Fragile X may notice Parent’s of infants with Fragile X may notice

hypersensitivity to light, sounds, touch, and hypersensitivity to light, sounds, touch, and texture.texture.

Many children have a strong negative reaction to Many children have a strong negative reaction to being held or to certain textures of clothing.being held or to certain textures of clothing.

High arousal levels to visually complex or crowded High arousal levels to visually complex or crowded environments, unpredictable events, and environments, unpredictable events, and maintenance of eye contact are also common. maintenance of eye contact are also common.

(The National Fragile X Foundation, 2006(The National Fragile X Foundation, 2006).).

Speech and LanguageSpeech and Language Difficulties with speech and language are common Difficulties with speech and language are common

in boys with fragile X syndrome.in boys with fragile X syndrome. Delays in speaking may be the first sign to parents Delays in speaking may be the first sign to parents

that something is wrong.that something is wrong. Boys may have difficulty with both speech and Boys may have difficulty with both speech and

hearing due to structural differences.hearing due to structural differences. Boys are also shown to have auditory processing Boys are also shown to have auditory processing

problems.problems. In girls, many areas of speech and language may In girls, many areas of speech and language may

be strengths. Language disorders that effect girls be strengths. Language disorders that effect girls with fragile X are usually in the area of with fragile X are usually in the area of conversation skills.conversation skills.

(The National Fragile X Foundation, 2006(The National Fragile X Foundation, 2006).).

Genetics of Fragile XGenetics of Fragile X

Fragile X Syndrome is an abnormality Fragile X Syndrome is an abnormality of the X chromosome that is the of the X chromosome that is the most frequent cause of mental most frequent cause of mental retardation except for Down retardation except for Down Syndrome Syndrome

(Sarason & Sarason, 1999).(Sarason & Sarason, 1999).

The gene effected is the FMR1 The gene effected is the FMR1 (The National Fragile X Foundation, 2006).(The National Fragile X Foundation, 2006).

Location of the FMR1Location of the FMR1

The FMR1 gene is located on the long (q) arm of chromosome X at position 27.3 .

Fragile X DetailsFragile X Details FMR1 is the gene that contains the genetic FMR1 is the gene that contains the genetic

information for how to process FMRP (fragile X information for how to process FMRP (fragile X mental retardation protein).  mental retardation protein). 

Fragile X syndrome occurs when FMRP is Fragile X syndrome occurs when FMRP is missing. missing.

People who do not have fragile X syndrome, People who do not have fragile X syndrome, make FMRP in some of their cells. Those cells make FMRP in some of their cells. Those cells that do make FMRP are regulated as to when that do make FMRP are regulated as to when they make it, so that it is present when needed they make it, so that it is present when needed in the places where it is needed.in the places where it is needed.

(The National Fragile X Foundation, 2005)(The National Fragile X Foundation, 2005)

Fragile X DetailsFragile X Details…(continued)…(continued)

The major characteristics observed in individuals The major characteristics observed in individuals with Fragile X Syndrome are related to the with Fragile X Syndrome are related to the functioning of the brain.functioning of the brain.

In individuals who do not have fragile X syndrome, In individuals who do not have fragile X syndrome, the brain and testicles are places where the protein the brain and testicles are places where the protein FMRP is actively synthesized. FMRP is actively synthesized.

In other words, humans typically make FMRP in the In other words, humans typically make FMRP in the testicles and the brain; if they can't, problems occur testicles and the brain; if they can't, problems occur and we call those problems fragile X syndrome. and we call those problems fragile X syndrome.

(The National Fragile X (The National Fragile X Foundation, 2005)Foundation, 2005)

What is Fragile X ?What is Fragile X ?

Researchers are not sure the exact role of Researchers are not sure the exact role of FMRP in cognitive and behavioral functioning.FMRP in cognitive and behavioral functioning.

There is evidence that it plays some role in There is evidence that it plays some role in regulating protein synthesis.regulating protein synthesis.

The existence of FMRP in the body is not The existence of FMRP in the body is not essential to an individual’s survival but it is a essential to an individual’s survival but it is a crucial componentcrucial component to typical cognitive and to typical cognitive and behavioral functioning. behavioral functioning.

Why Why Fragile XFragile X??

Fragile X gets its name from the fact that Fragile X gets its name from the fact that the X chromosome, of the individual the X chromosome, of the individual affected, will show a fragile spot when affected, will show a fragile spot when grown in a lab culture grown in a lab culture

(Sarason & Sarason, 1999). (Sarason & Sarason, 1999).

Also, the X chromosome breaks in two, Also, the X chromosome breaks in two, making it “fragile” .making it “fragile” .

(Davison, Neale, & Kring, (Davison, Neale, & Kring, 2004)2004)

How do you get Fragile X?How do you get Fragile X? Fragile X syndrome is transmitted Fragile X syndrome is transmitted

from parent to child through the from parent to child through the genetic information (DNA) that is genetic information (DNA) that is present in the sperm and egg. present in the sperm and egg.

The X chromosome is part of the sex The X chromosome is part of the sex chromosome pair. This determines chromosome pair. This determines the sex of the individual.the sex of the individual.

(Sarason & Sarason, 1999).(Sarason & Sarason, 1999).

InheritanceInheritance

Women have 2 X chromosomes Women have 2 X chromosomes Men have 1 X and 1 Y chromosomeMen have 1 X and 1 Y chromosome

If only 1 of the mother’s X If only 1 of the mother’s X chromosome is effected by Fragile X chromosome is effected by Fragile X Syndrome, the mother may not have Syndrome, the mother may not have mental retardation but may be a mental retardation but may be a carrier of Fragile X Syndrome.carrier of Fragile X Syndrome.

Inheritance Inheritance (continued…)(continued…)

Since one of the sex chromosome pair Since one of the sex chromosome pair comes from each parent, if a man has comes from each parent, if a man has Fragile X Syndrome it must have been Fragile X Syndrome it must have been transmitted through his mother.transmitted through his mother.

Because girls have two X Because girls have two X chromosomes, one from each parent, chromosomes, one from each parent, female children are less likely to be female children are less likely to be affected by fragile X syndrome.affected by fragile X syndrome.

Fragile X and the BrainFragile X and the Brain Children with Fragile X have been Children with Fragile X have been

reported to have larger hippocampal reported to have larger hippocampal volumes than individuals without volumes than individuals without fragile Xfragile X

Geuze, Vermetten, & Bremner, 2005

Fragile X and The BrainFragile X and The Brain Priliminary studies from imaging studies out Priliminary studies from imaging studies out

of Stanford suggest an association between of Stanford suggest an association between the the FMR1FMR1 mutation and abnormalities of mutation and abnormalities of particular neuroanatomical regions.particular neuroanatomical regions.

Individuals with fragile X demonstrate Individuals with fragile X demonstrate abnormalities of the fourth and lateral abnormalities of the fourth and lateral ventricles, hippocampus, amygdalaventricles, hippocampus, amygdala

Fragile X and the Brain Fragile X and the Brain (cont.)(cont.)

Working memoryWorking memory

During a memory task, where subjects must During a memory task, where subjects must remember the location of objects, compared to remember the location of objects, compared to “typical” control subjects, subjects with fragile X “typical” control subjects, subjects with fragile X have significantly reduced activation in the have significantly reduced activation in the frontal and parietal brain regions.frontal and parietal brain regions.

Subject with Fragile X

Subject who is “Typical”

Response inhibitionResponse inhibitionDuring a response inhibition task, where subjects During a response inhibition task, where subjects

must with-hold response to particular stimuli, must with-hold response to particular stimuli, compared to “typical” control subjects, subjects compared to “typical” control subjects, subjects with fragile X have significantly reduced with fragile X have significantly reduced activation in the prefrontal cortexactivation in the prefrontal cortex

Subject with Fragile X

“Typical”

Subject

The BrainThe Brain One area that children will Fragile X have a particularly One area that children will Fragile X have a particularly

difficult time with is Math. difficult time with is Math. Studies are being done to take a closer look at this.Studies are being done to take a closer look at this.

Educational ImplicationsEducational Implications

Perceived as being difficult to accommodate within a class room Perceived as being difficult to accommodate within a class room setting or environment setting or environment

Having an informed understanding of their individual and specific Having an informed understanding of their individual and specific difficulties can help teachers and peers adapt - impaired ability to difficulties can help teachers and peers adapt - impaired ability to organize and select incoming sensory information organize and select incoming sensory information

Better on tasks that require vocabulary knowledge and verbal Better on tasks that require vocabulary knowledge and verbal reasoning - tend to perform better on spelling tasks and readingreasoning - tend to perform better on spelling tasks and reading

Benefit from a more visually based, experiential or holistic learning Benefit from a more visually based, experiential or holistic learning style – visually presented material style – visually presented material

Perform poorly on tasks that involve abstract reasoning – Perform poorly on tasks that involve abstract reasoning – mathematicsmathematics

(Saunders, 1999)

Educational Implications Educational Implications cont.cont.

To Facilitate Learning…To Facilitate Learning…

Need a high level of assistance to keep them organized and on task - Need a high level of assistance to keep them organized and on task - high level of distractibility makes this hard for them to accomplish on high level of distractibility makes this hard for them to accomplish on their owntheir own

Direct pressure on the student (time limits, questions in front of Direct pressure on the student (time limits, questions in front of others, and insistence on collaboration) can often cause adverse others, and insistence on collaboration) can often cause adverse reactions from studentreactions from student

Often find writing to be difficult and alternative recording methods (i.e. Often find writing to be difficult and alternative recording methods (i.e. computer) can help them demonstrate their actual knowledgecomputer) can help them demonstrate their actual knowledge

Often have a good memory for things that capture their interest and Often have a good memory for things that capture their interest and excel in subjects that particularly interest themexcel in subjects that particularly interest them

(Saunders, 1999)(Saunders, 1999)

Educational Implications Educational Implications cont.cont.

Classroom Environment…Classroom Environment…

Benefit from a quiet, calm, and orderly classroom – with a minimum Benefit from a quiet, calm, and orderly classroom – with a minimum amount of noise and disruptionamount of noise and disruption

Benefit from a clear and consistent routine that is predictable to the Benefit from a clear and consistent routine that is predictable to the studentstudent

Benefit tremendously from having their own space within the Benefit tremendously from having their own space within the classroom that they can retreat to when neededclassroom that they can retreat to when needed

Often become upset or distressed when other students in the Often become upset or distressed when other students in the classroom are upset or get in trouble – they dislike fights or classroom are upset or get in trouble – they dislike fights or arguments amongst other studentsarguments amongst other students

(Saunders, (Saunders, 1999)1999)

Educational Implications Educational Implications cont.cont.

BehaviorallyTo Avoid Problem Behaviors…To Avoid Problem Behaviors…

Know the student’s individual triggers and plan to avoid them or Know the student’s individual triggers and plan to avoid them or offer special help to enable student to cope with certain situationsoffer special help to enable student to cope with certain situations

Allow student some freedom to roam about the classroom and Allow student some freedom to roam about the classroom and engage in some “off-task” behavior when necessaryengage in some “off-task” behavior when necessary

Give the student their own personal space and, when needed, seat Give the student their own personal space and, when needed, seat him or her away from other pupilshim or her away from other pupils

(Saunders, (Saunders, 1999)1999)

Educational Implications Educational Implications cont.cont.

ToTo Restore Order After Behavioral Problems…Restore Order After Behavioral Problems…

Remove the student from the scene of the disturbance, preferably out Remove the student from the scene of the disturbance, preferably out of the room, or to a place where he or she feels ‘safe’of the room, or to a place where he or she feels ‘safe’

A familiar and trusted adult should remain close and talk to the student A familiar and trusted adult should remain close and talk to the student in order to help calm him or her in order to help calm him or her

Distract the student with familiar and enjoyable objects, tasks, and Distract the student with familiar and enjoyable objects, tasks, and activitiesactivities

Allow the student time and freedom to do what they need to do in Allow the student time and freedom to do what they need to do in order to restore and regain their self-control, before returning them to order to restore and regain their self-control, before returning them to the classthe class

When the student appears to become calmer, humor can often help When the student appears to become calmer, humor can often help restore normalityrestore normality

(Saunders, 1999)(Saunders, 1999)

The Faces of Fragile XThe Faces of Fragile X

Video clip:Video clip: http://www.youtube.com/watch?http://www.youtube.com/watch?

v=wGdH1M5lCVYv=wGdH1M5lCVY

Find Out More…Find Out More…

National Fragile X FoundationNational Fragile X Foundation http://www.fragilex.org/html/home.shtmlhttp://www.fragilex.org/html/home.shtml

Center for Human DevelopmentCenter for Human Development http://www.cdc.gov/ncbddd/single_gene/fragilex.htmhttp://www.cdc.gov/ncbddd/single_gene/fragilex.htm

Fragile X Research FoundationFragile X Research Foundation http://www.fraxa.org/http://www.fraxa.org/