Fragile X syndrome causes mild to severe intellectual disability. It affects both males and females, but females usually have milder symptoms. Symptoms include delays in talking, anxiety and hyperactive behaviour. Some people have seizures. Physical features might include large ears, a long face, a prominent jaw and forehead and flat feet. Therapy can be used to treat learning disabilities. Medication may be used to treat anxiety and mood disorders.

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CONTENT OF THE TERM PAPER
Preface to the Term Paper 1
Acknowledgement 2
Introduction 3
Brief introduction about “FRAGILE X SYNDROME” 4
Signs and symptoms 5
Causes 9
Diagnosis 9
Management 9
Reference 10

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✓ INTRODUCTION:
Fragile X syndrome (FXS) is a genetic disorder. Symptoms often include
mild to moderate intellectual disability. Physical features may include
a long and narrow face, large ears, flexible fingers, and large testicles.
About a third of those affected have features of autism such as
problems with social interactions and delayed speech. Hyperactivity is
common and seizures occur in about 10%. Males are usually more
affected than females.
✓A brief introduction about
“FRAGILE X SYNDROME ”:

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Fragile X syndrome is typically due to an expansion of the CGG triplet
repeat within the Fragile X mental retardation 1 (FMR1) gene on the X
chromosome. This results in not enough fragile X mental retardation
protein (FMRP), which is required for normal development of the
connection between neurons. Diagnosis is by genetic testing to
determine the number of CGG repeats in the FMR1 gene. Normal is
between 5 and 40 repeats, fragile X syndrome occurs with more than
200, and a premutation is said to be present when a middle number
of repeats occurs. Testing for premutation carriers may allow for
genetic counselling.
There is no cure. Early intervention is recommended as it provides the
most opportunity for developing a full range of skills. These
interventions may include special education, speech therapy, physical
therapy, or behavioural therapy. Medications may be used to treat
associated seizures, mood problems, aggressive behaviour, or ADHD.
Fragile X syndrome is estimated to occur in 1.4 in 10,000 males and
0.9 in 10,000 females.
✓ SIGNS AND SYMPTOMS :
Prominent characteristics of the syndrome include an elongated face,
large or protruding ears, and low muscle tone.Most young children do
not show any physical signs of FXS. It is not until puberty that physical
features of FXS begin to develop. Aside from intellectual disability,
prominent characteristics of the syndrome may include an elongated
face, large or protruding ears, flat feet, larger testes (macroorchidism),
and low muscle tone. Recurrent otitis media (middle ear infection) and
sinusitis is common during early childhood. Speech may be cluttered
or nervous. Behavioral characteristics may include stereotypic
movements (e.g., hand-flapping) and atypical social development,
particularly shyness, limited eye contact, memory problems, and

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difficulty with face encoding. Some individuals with fragile X syndrome
also meet the diagnostic criteria for autism.
Males with a full mutation display virtually complete penetrance and
will therefore almost always display symptoms of FXS, while females
with a full mutation generally display a penetrance of about 50% as a
result of having a second, normal X chromosome. Females with FXS
may have symptoms ranging from mild to severe, although they are
generally less affected than males.
✓Physical phenotype :
• Large, protruding ears (both)
• Long face (vertical maxillary excess)
• High-arched palate (related to the above)
• Hyperextensible finger joints
• Hyperextensible ('double-jointed') thumbs
• Flat feet
• Soft skin
• Postpubescent macroorchidism (large testicles in men after
puberty)
• Hypotonia (low muscle tone)
✓Autism:
Fragile X syndrome co-occurs with autism in many cases and is a
suspected genetic cause of the autism in these cases. This finding
has resulted in screening for FMR1 mutation to be considered
mandatory in children diagnosed with autism. Of those with fragile
X syndrome, prevalence of concurrent autism spectrum disorder
(ASD) has been estimated to be between 15 and 60%, with the
variation due to differences in diagnostic methods and the high
frequency of autistic features in individuals with fragile X syndrome
not meeting the DSM criteria for an ASD.

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✓Neurological:
Individuals with FXS are at a higher risk of developing seizures, with
rates between 10% and 40% reported in the literature. The seizures
tend to be partial, are generally not frequent, and are amenable to
treatment with medication.
✓Vision:
Ophthalmologic problems include strabismus. This requires early
identification to avoid amblyopia.
✓Social interaction:
FXS is characterized by social anxiety, including poor eye contact, gaze
aversion, prolonged time to commence social interaction, and
challenges forming peer relationships. Social anxiety is one of the
most common features associated with FXS.
✓Psychiatric :
Attention deficit hyperactivity disorder (ADHD) is found in the
majority of males with FXS and 30% of females, making it the most
common psychiatric diagnosis in those with FXS. Hyperactivity and
disruptive behaviour peak in the preschool years and then gradually
decline with age, although inattentive symptoms are generally
lifelong.
✓Fertility:
About 20% of women who are carriers for the fragile X premutation
are affected by fragile X-related primary ovarian insufficiency (FXPOI),
which is defined as menopause before the age of 40. The number of

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CGG repeats correlates with penetrance and age of onset. However
premature menopause is more common in premutation carriers than
in women with the full mutation, and for pre-mutations with more
than 100 repeats the risk of FXPOI begins to decrease. Fragile X-
associated primary ovarian insufficiency (FXPOI) is one of three Fragile
X-associated Disorders (FXD) caused by changes in the FMR1 gene.
FXPOI affects female premutation carriers of Fragile X syndrome,
which is caused by the FMR1 gene, when their ovaries are not
functioning properly. Women with FXPOI may develop menopause-
like symptoms but they are not actually menopausal. Women with
FXPOI can still get pregnant in some cases because their ovaries
occasionally release viable eggs.
✓Working memory:
From their 40s onward, males with FXS begin developing progressively
more severe problems in performing tasks that require the central
executive of working memory.

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✓ Causes :
Fragile X syndrome is a genetic disorder which occurs as a result of a
mutation of the fragile X mental retardation 1 (FMR1) gene on the X
chromosome, most commonly an increase in the number of CGG
trinucleotide repeats in the 5' untranslated region of FMR1.
Location of FMR1 gene on the X chromosome
✓ Diagnosis :
Cytogenetic analysis for fragile X syndrome was first available in the late 1970s
when diagnosis of the syndrome and carrier status could be determined by
culturing cells in a folate deficient medium and then assessing for "fragile sites"
(discontinuity of staining in the region of the trinucleotide repeat) on the long
arm of the X chromosome.
✓ Management :
There are no cure for the underlying defects of FXS. Management of FXS may
include speech therapy, behavioural therapy, sensory integration occupational
therapy, special education, or individualised educational plans, and, when
necessary, treatment of physical abnormalities. Persons with fragile X syndrome
in their family histories are advised to seek genetic counselling to assess the
likelihood of having children who are affected, and how severe any impairments
may be in affected descendants.

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✓ Reference:
i. Textbook of Biochemistry by U Satyanarayana
ii. Lippincott illustratated reviews Biochemistry
iii. Harpers Illustrated Biochemistry
iv. https://en.wikipedia.org/
v. https://ghr.nlm.nih.gov/
vi. ahttp://www.llamp.net