WHAT IS FRAGILE SYNDROME
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Dear Fragile X Syndrome Spanish families, Greetings from the University of California at Davisâ€™ 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?
2 . WHAT CAUSES FRAGILE X SYNDROME ?
3. WHICH ARE THE MAIN CHARACTERISTICS OF FXS?
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
3.3 . SOCIAL AND
3.4 . LANGUAGE AND
4 . IS THERE A TREATMENT FOR FXS?
1. WHAT IS FRAGILE X SYNDROME
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.
â€œcounteractâ€? 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.
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
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
all patients. The varying degree of the different clinical characteristics may sometimes make the diagnostic process
of FXS can be divided into five
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
Language and Speech Problems
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
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
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,
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.
and/or large testicles.
Hyperactivity during childhood.
Lack of concentration.
Long and asymmetric face.
Speech perseverance, repetitive speech.
Some autistic like disorders with lack of social interaction.
Convulsions and epilepsy.
Younger males and females, carriers
Poor eye contact.
of the mutation, may also show some of
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,
3.3 .SOCIAL AND BEHAVIOURAL TRAITS
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
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.
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
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
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.
4 . IS THERE A TREATMENT
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
acquisition of learning skills and the overall
useful in the treatment of hyperactivity,
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
Mercè Bellavista and Carles Fauró
Dra. Montse Milà and Dr. Josep Artigas
Katy Garcia and Eugenia Rigau
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