Leaflet nº1. What is Fragile X Syndrome?

WHAT IS FRAGILE SYNDROME

With the support of:

INDE X

Dear Fragile X Syndrome Spanish families, Greetings from the University of California at Davis’ MIND Institute. Fragile X Syndrome diagnosis opens new therapeutic possibilities which will be of great help to your children. Knowledge is powerful and it is important to read and acquire such knowledge on the syndrome. The Catalan Fragile X Syndrome Association has become one of the most solid organisations in Europe and can provide different means of support to facilitate access to information that can greatly improve the treatment of children or adults affected by this syndrome.

I look forward to seeing you again in future meetings,

1. WHAT IS FRAGILE X SYNDROME?

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2 . WHAT CAUSES FRAGILE X SYNDROME ?

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3. WHICH ARE THE MAIN CHARACTERISTICS OF FXS?

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3.1 . COGNITIVE

3.2 . PHYSICAL

Best wishes, Randi Hagerman MD Endowed chair in Fragil X research Medical director of the MIND Institut UCDavis medical center

CAPABILITIES

CHARACTERISTICS

3.3 . SOCIAL AND

BEHAVIOURAL TRAITS

3.4 . LANGUAGE AND

3.5. SENSORY

SPEECH PROBLEMS

ASPECTS

4 . IS THERE A TREATMENT FOR FXS?

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1. WHAT IS FRAGILE X SYNDROME

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2 . WHAT CAUSES

FRAGILE X SYNDROME ?

Fragile X Syndrome (FXS) is the most common cause of inherited mental retardation.

FXS results from a mutation in a gene

latter normally to a lesser extent. The

located on the X chromosome, so it is a

carriers of a pre-mutation have normal

sex linked disease. Women have two X

production of FMRP (the protein) and

This syndrome is caused by a lack of a protein called FMRP (Fragile X Mental Retardation Protein), which is synthesized by the FMR1 (Fragile X Mental Retardation 1) gene and is necessary throughout our lives.

chromosomes while men have one X and

thus, do not suffer from FXS.

one Y chromosome. This is the reason

Expansion of over 200 repeats in the gene

why the clinical manifestations of the

causes the disruption of FMRP production,

syndrome are different between males

and no protein can be synthesised from

and females. Women can somewhat

the gene, resulting in FXS. Every mother

compensate the deficit caused by the

of an affected child is a carrier of FXS

mutated X chromosome with the normal

and has a 50% risk in every pregnancy

In the general population 1 in every

one, and men, having only one X, cannot

to have a baby affected by FXS, this is

2500 men, and 1 in 8000 women suffer from mental retardation caused by FXS.

“counteract� the deleterious effect of the

the same level of risk for every carrier girl.

FXS can cause cognitive deficits which may range from subtle challenges in learning capacity to moderate or profound mental retardation. Even though mental retardation is the most characteristic symptom, the clinical manifestations of FXS are much more complex.

One in every 400 women and 1 in 1200 men in the general population are healthy carriers of the disorder.

Approximately one third of the The initial diagnosis of FXS is based on the cognitive, behavioural and physical phenotype, but it must always be confirmed by a genetic study of the FMR1 gene, which can be done by molecular biology techniques from a blood sample.

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women that carry the full mutation may show some degree of cognitive deficits, from mild to severe.

FXS is a congenital disorder, it is first noticed during early infancy irrespective of race or socioeconomic level.

mutation. The FMR1 gene has a limited number of repeats of the trinucleotide CGG (cytosine-guanine-guanine). In the general population, the normal number of CGG repeats is between 6 and 52. In the situation known as pre-mutation, the number of repeats ranges from 53 to 200.

From this number of repeats, further expansions of more than 200 CGG repeats can be passed on to the progeny, and this is considered a full mutation, which affects both men and women, the

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FXS healthy carrier men have no risk of

nosis and in some cases, pre-implantation

having mentally retarded progeny in the

diagnosis. Once a child is diagnosed as ha-

first generation, but all daughters will be

ving FXS, it is advisable to study the whole

carriers of the mutation.There are curren-

family, mother, siblings and maternally re-

tly different reproductive options for carrier

lated extended family, in order to guarantee

mothers, like egg donation, prenatal diag-

genetic counselling when needed.

3. WHICH ARE THE MAIN

CHARACTERISTICS OF FXS ?

3.1

Cognitive Capabilities

all patients. The varying degree of the different clinical characteristics may sometimes make the diagnostic process

3.2

of FXS can be divided into five

3.3

3.4

Physical Characteristics

drawings), and this they use to recognize

which will affect their capacity to think,

letters and words. They are generally able

reason or learn. The degree to which

to follow orders and commands if

this cognitive ability may be affected

presented in a visual form, like drawings.

depends on the variations of the FMR1

However, they show difficulty in organising

gene mutation and the amount of protein

information, working on more abstract

that can be synthesized from it. The

concepts or solving problems.

majority of affected males show some to severe, combined with speech and half of all affected females will also manifest some level of cognitive

Social and Behavioural

but show learning difficulties, particularly

Traits

in maths.

Language and Speech Problems

categories:

3.5

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some degree of mental impairment

impairment, others may have normal IQ

very difficult.

In general terms, the clinical aspects

very strong visual memory (images and

language difficulties. Approximately one

individual to individual, though some features are shared to some degree by

People with FXS very often suffer from

degree of mental retardation, from mild

The nature and degree of the clinical manifestations of FXS can differ from

3.1 . COGNITIVE CAPABILITIES

Sensory Aspects

Together with the intellectual delay,

In order to develop their learning abilities,

there is a full cognitive profile

people with FXS need more time for

consisting of strong and soft points

learning, and they benefit from adapted

for each individual. For example, the

learning methods and favourable

vast majority of people with FXS have

environments.

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3.2 . PHYSICAL CHARACTERISTICS

IT IS VERY IMPORTANT:

To know the learning style or

People with FXS may show different

and heart problems due to lax valves

profile of every person.

characteristic physical features,

(mitral valve prolapse). The physical

To stick to a routine and an

although they may not all be present in

traits can be very subtle and often,

one same person. Adult men may have

FXS boys and adults may have a totally

a longer face, large or sticking-out ears,

normal appearance.

organising scheme in a calendar.

To use visual clues and defined examples to present ideas or concepts and to follow a gradual and stepwise approach.

To prepare the person if there is to be a change of routines, explaining such changes well in advance and with clear visual clues.

To provide functional learning.

To allow time for the person to move around or to leave the classroom at certain times during the day.

To use computers while learning.

To provide the quietest possible environment.

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MOST FREQUENT

and/or large testicles.

CHARACTERISTICS

MOST FREQUENT

Hyperactivity during childhood.

CHARACTERISTICS

Lack of concentration.

Long and asymmetric face.

Learning disabilities.

Thin lips.

Speech perseverance, repetitive speech.

Prominent jaws.

Some autistic like disorders with lack of social interaction.

Large heads.

Convulsions and epilepsy.

Large foreheads.

Aggressiveness.

Younger males and females, carriers

Poor eye contact.

of the mutation, may also show some of

Nail biting.

these characters. There are often

Hearing problems derived from ear infections.

abnormalities in connective tissue,

Large ears.

Strabismus.

Irregular teething.

including double finger joints, flat feet,

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3.3 .SOCIAL AND BEHAVIOURAL TRAITS

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Kids with FXS show a characteristic

Behavioural traits are highly varied and

behavioural phenotype from a very early

can range from socially acceptable and

age. They are particularly sensitive to

friendly to autistic like with aggressive

sensory stimuli, which may trigger

fits.

tantrums under certain circumstances.

Many kids with FXS, particularly boys,

They may also have different autistic

have social anxiety, they dislike meeting

traits associated, like poor eye contact,

new people or doing new things not

hypersensitivity to touch and defence

previously planned. The level of anxiety

from physical contact, stereotypes,

can be very high and they can then totally

perseverance and repetition both in

avoid social activities or gatherings.

speech and behaviour.

When these kids interact with other people they often feel uncomfortable and anxious,

tions can help control such behaviours.

and this causes them to avoid eye contact

Girls with FXS tend to be more

and present repetitive speech.

introverted and shy and they also

Unexpected changes in routine can

suffer from more anxiety than boys

cause profound stress in these kids,

before social situations.

represents, for the vast majority of FXS

unless they have been warned of such

In some occasions, excessive shyness

patients, a high social stimulus which is

changes in advance. Some children

and anxiety can result in selective mutism,

hard to integrate. This is why they show

respond with tension, others have

which prevents them from speaking in

a clear tendency to avoid or divert eye

tantrums, cry desperately or initiate

social situations, like at school.

contact. They are often hypersensitive to

repetitive movements endlessly. Being

People with FXS can easily feel anxious

sounds and touch, and to the consistency

able to provide a quiet environment

by sensory stimuli. Very often these stimuli

and feel of certain foodstuffs.

and foreseeing and warning the

consist of loud sounds and noises, which

Hyperactivity and impulsiveness are

children in advance of certain situa-

will affect their behaviour. Eye contact

very common in FXS affected people.

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3.4 . LANGUAGE AND SPEECH PROBLEMS

cases they never acquire language skills.

shyness and anxiety will hamper social

For those kids with no language abilities

interaction and non-verbal communication

Language and speech difficulties can

circumstances they talk very fast or very

it is important to work and provide other

with other people, leading to situations

range from simple stuttering to severe

loud.

means of alternative communication in

like, not respecting turns to talk or failing

impairment, with pronunciation problems

Some of these difficulties can be

order to reduce behavioural traits caused

the answer if there are questioned about

and inability to organize sentences or to

caused by sensory problems or by

by language deficit.

something they know, or to leave the

use correct grammar, leading to

anxiety, and may not derive directly

Girls with FXS seldom have severe

group before they have finished a con-

generalized language problems.

from a particular problem in the

language deficits, which enables them

versation, because they do not under-

Avoidance of certain sounds in words,

language area of the brain.

to acquire reading and writing skills, but

stand what they are supposed to do.

constant repetition of the same word or

For some children these problems are

the same question, or starting a phrase

more severe and they do not start to talk

that they have already started, are also

before age four. Sometimes they do not

very common problems. Under particular

talk until age between 6 to 8. In some

3.5. SENSORY ASPECTS Most girls and boys with FXS are very sensitive to certain sensory inputs.

They can become very fidgety and nervous if they hear a very loud or very soft sound.

They can be made to feel very uncomfortable by the texture of the clothes they are wearing when contact is made with their skin, or by making them drink directly from a bottle

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because of the feeling on their lips. Some of

aspects may accompany them for the rest

these kids will refuse to be touched or hugged.

of their lives, they can be improved by a

Even though some of these sensory

good sensory intervention programme.

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4 . IS THERE A TREATMENT

FOR FXS

?

still forming and retains much plasticity.

So, irrespective of the age at which the diagnosis comes, it is never too late to benefit from intervention. Many people with FXS have problems processing sensory and perceptive inputs so that, the way in which they receive information, their ability to use it for learning, or the behaviour derived from this information, is distorted. It is thus very important to Research in this field is constantly bringing

use techniques of sensory integration to

new scientific data on FXS, but it has not

help prevent these problems.

yet come to provide an effective and

Treatment is applied mainly by ways of

curative therapy. It is important to evaluate

different types of therapy, including special

the different learning abilities, behavioural

education, language and speech

problems and medical needs of every kid

intervention, behavioural correction,

with FXS individually in order to provide

cognitive treatment, occupational therapy

the most suited intervention and therapy

and physical therapies. Medical

programme. The sooner the intervention

intervention, based on the use of stimulant

Illustrations and English

is started the greater the benefits on

and anti-depressive drugs, can be very

translation:

Marc Isamat

acquisition of learning skills and the overall

useful in the treatment of hyperactivity,

Design:

Vargas*comunicació

results of the intervention programme,

attention deficit, anxiety and compulsive

since the brain during early childhood is

obsessive disorders in persons with FXS.

Coordination: Caf Gestión: Laura Berga and Mercedes Aldecoa

Direction:

Mercè Bellavista and Carles Fauró

Advisors:

Dra. Montse Milà and Dr. Josep Artigas

Contents:

Katy Garcia and Eugenia Rigau

Print: 12

Òpal Gràfic

With the support of: