Download The Inheritance of the Fragile X Gene

Saint Mary’s Hospital
Manchester Centre for Genomic Medicine
The Inheritance of the
Fragile X Gene
Information For Patients
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Introduction
This leaflet describes the way the Fragile X (FraX) gene is passed
on in families. It also describes the different forms of the gene
and the effect these different forms can have. It does not
include detailed information about the symptoms of Fragile X
syndrome or advice for management. The Fragile X Society has
produced excellent booklets about many aspects of the
condition in a variety of languages (www.FragileX.org.uk).
Inheritance
Fragile X is a genetic inherited and is caused by an alteration
(sometimes called a change, mutation or expansion) in the
Fragile X gene. Genes are the instructions our bodies use to
grow and develop. All of our genes are packaged on structures
called chromosomes. The Fragile X gene is found on the X
chromosome. Women have two X chromosomes and men have
one X and one Y chromosome. This means that women have
two copies of the Fragile X gene while men have only one.
When men have children they pass on their X chromosome to all
their daughters and their Y chromosome to all their sons. When
women have children they pass on one or other of their X
chromosomes to each of their children.
The Fragile X gene
The Fragile X gene varies in size and, based on this, is described
as normal, premutation or full mutation. Below we describe how
the size of the Fragile X gene affects men and women
differently and how each might pass the gene on.
1. Men who have a Full Mutation
Men who inherit a full mutation will have Fragile X syndrome.
The range and severity of symptoms varies widely and cannot
be predicted by a genetic test. Men with a full mutation are
usually infertile. If they do have children, their daughters will all
carry a premutation but their sons will not be affected or be
carriers of Fragile X syndrome.
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2. Women who have a Full Mutation
Only about 50% or 1 in 2 women who have inherited a full
mutation have symptoms of Fragile X syndrome. This is because
they also have a second (usually normal) copy of the fragile X
gene which can compensate. Women who are affected usually
experience less severe symptoms than men who are affected,
but this is not always the case. The genetic test cannot tell us
whether or not a woman with the full mutation will have
symptoms of Fragile X syndrome.
If a woman with a full mutation has children, there is a 50% (1
in 2) chance of her passing on the X chromosome with the
full mutation to her child (see diagram 1). What this means for
the child will depend on whether they are male or female
(see below).
Diagram 1: Possible outcomes when a woman with a full
mutation has children
Male Partner – Non Carrier
Female with a Full Mutation
X Y
1 in 4 chance
of a daughter
without a
full mutation
(unaffected)
XX
1 in 4 chance of a
daughter with a
full mutation
(50% or 1 in 2 of
these will have
symptoms of
Fragile X)
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1 in 4 chance
of a son
without a
full mutation
1 in 4 chance
of a son
with a full
mutation
(unaffected) (affected)
3. Men who have a Premutation
Men who have a premutation do not have Fragile X syndrome
(but some studies suggest there may be a link to some mild
symptoms such as anxiety in social situations). When a man
passes on a premutation it remains the same size. A man with a
premutation will pass on his X chromosome (carrying the
premutation) to all of his daughters, but his Y chromosome
(without a Fragile X gene) to all of his sons (see diagram 2). This
means a man with a premutation is not at risk of having a child
with Fragile X syndrome, but his grandchildren, born to his
daughters, could be affected.
A proportion of men who have a premutation develop problems
with movement, balance and/or memory later on in life. The
chance of this happening increases with age. The majority of
men with a premutation will have some problems over age 70.
This condition is called FXTAS (Fragile X Tremor Ataxia
Syndrome) and although it is due to the Fragile X gene, the
symptoms are very different to Fragile X syndrome.
If you have concerns regarding symptoms experienced by you or
a family member, either get in touch with your genetics doctor/
counsellor or discuss your concerns with your GP.
A link between being a premutation carrier and thyroid
problems has been described. If you have never had a check of
your thyroid function, your GP could arrange testing for you.
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Diagram 2: Possible Outcomes when a man with a Premutation
has children
Male with a Premutation
Female Partner – Non Carrier
X Y
XX
1 in 2 chance of a daughter
1 in 2 chance of a son
(all daughters unaffected
(all sons will be unaffected
but will have a premutation) non-carriers)
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4. Women who have a Premutation
Women who have a premutation do not have Fragile X
syndrome (but some studies suggest there may be a link to some
mild symptoms such as anxiety in social situations). A woman
with a premutation has a 50% (1 in 2) chance of passing on the
premutation to each of her children. When passed on by a
woman a premutation will either stay the same size or may get
bigger and become a full mutation.
If a woman passes on a premutation unchanged, her child (male
or female) will be a carrier of a premutation but will not have
Fragile X syndrome. If the premutation becomes a full mutation
when it is passed on to a son, the son will be affected by Fragile
X syndrome. If the premutation becomes a full mutation when it
is passed to a daughter, there is a 50% (1 in 2) chance that she
will have symptoms of Fragile X syndrome (see diagram 3).
It is not possible to accurately predict the chance of a gene
changing from a premutation to a full mutation when it is
passed on, although in general the larger the premutation the
more likely it is to increase into the full mutation range when it
is passed on.
Some women with a premutation can have fertility problems
and/or an earlier menopause than usual. Women who are
concerned about their fertility can be referred to a doctor in
Reproductive Medicine at Saint Mary’s Hospital for an
assessment of their ovarian function. Women who are concerned
about possible early menopausal symptoms can be referred to
an Endocrinologist based at Christie Hospital for an assessment.
A small proportion of women with a premutation develop
problems with movement, balance and/or memory associated
with FXTAS similar to those seen in a larger proportion of men
with a premutation (see section 3). A link between being a
premutation carrier and thyroid problems has been described
and if you have never had a check of your thyroid function it
would be advisable to ask your GP for at least a one-off test.
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Diagram 3: Possible Outcomes when a woman with a
Premutation has children
Male Partner Female with a
Non CarrierPremutation Carrier
X Y
1 in 4 chance
of a daughter
with 2
normal X
chromosomes
XX
1 in 4
chance of
a son with
a normal X
chromosome
1 in 4 chance
of a daughter
with EITHER a
premutation OR a
full mutation (see
text section 4)
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1 in 4 chance
of a son with
EITHER a
premutation
OR a full
mutation (see
text section 4)
The Fragile X Society
The Fragile X Society provides information and support for
individuals with Fragile X and their families. You can contact
them at the following address:
The Fragile X Society
Rood End House
6, Stortford Road
Great Dunmow
Essex CM6 1DA
Tel: 01371 875100
E-mail: [email protected]
Website: www.fragilex.org.uk
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Zero Tolerance Policy
We are committed to the well-being and safety of our patients
and of our staff. Please treat other patients and staff with the
courtesy and respect that you expect to receive. Verbal abuse,
harassment and physical violence are unacceptable and will lead
to prosecutions.
Suggestions, Concerns and Complaints
If you would like to provide feedback or have a complaint there
are several options available to you:
• Speak to the ward or department manager –
they may be able to help straight away.
• Contact our Patient Advice and Liaison Service (PALS) –
Tel: (0161) 276 8686 e-mail: [email protected]. Ask for our
information leaflet which can also be found in the hospital.
• Through the NHS Choices website www.nhs.uk by clicking
on the ‘Comments’ section.
We welcome your feedback so we can continue to improve
our services.
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Notes
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TIG 102/11 Produced September 2014 Review
12 Date September 2016 (SF Taylor CM12825)