1. What is FSH-MD?
is a muscle wasting condition, caused by a genetic fault, which may
be affecting the regulation of the level of many of the different proteins
2. Why this name,
and are there others?
describes the usual distribution of weakened muscles: facio=facial;
scapulo=shoulder blade; humeral= upper arm.
Landouzy-Dejerine and facioscapuloperoneal muscular dystrophy are two
previously used terms. Also, some people with a diagnosis of scapulohumeral
or scapuloperoneal syndromes may have this condition. However, the legs
can also be affected.
3. How rare is
probably the third most common muscular dystrophy (after Duchenne and
myotonic dystrophies), although its frequency may vary in different
places and quite possibly in different racial groups. Estimates of frequency
have varied from one in about 400,000 to one in 20,000. In Britain,
the frequency is at least one person in every 50,000, and probably closer
to one in 20,000, accounting for between about 1200 and 3000 cases in
4. What causes
It is a genetic
condition, present from when or soon after egg and sperm come together
at conception. Normally, at a particular site on the gene map, each
of us has many copies of a particular sequence of genetic instruction
(DNA), arranged like a train of identical carriages. FSHD is caused
when the number of copies is reduced below a certain level, like a train
having too few carriages. In some way this seems to influence the production
or assembly of several of the protein components of the affected muscles.
5 .How severe
or mild is it?
of weakness or disability can vary quite widely between different affected
members in a family, but can show even greater variation between people
in different families. For some, it can result in weakness not only
of facial muscles and shoulders/upper arms, but also of additional combinations
from the neck, forearms, wrists, fingers, hips, legs, ankles and the
back muscles. Around 10-20% of people eventually require a wheelchair,
but by contrast, up to one third remain unaware of symptoms at least
into old age, although may well have subtle detectable clinical signs.
The majority of people come between these two extremes. The average
severity of presentation in a family, or in a single case, seems to
correlate with the smallness of the number of copies of the DNA repeat
sequence which remain (i.e. the fewer copies left, the greater is the
In general, the
most severely affected people tend to be the ones who have the altered
genetic instruction for the first time in the family, and where the
symptoms of weakness are evident from early childhood.
6. Are men and
women affected equally?
We now know
that, on average, men do tend to show more weakness and from a slightly
earlier age than women. The reason for this is not yet clear. Within
large families, and therefore excluding the most severe cases, women
are more likely to be less severely affected and so could be unaware
that they have inherited the condition.
7. What are the
mildest signs that someone is affected?
Within the context
of a family history of FSHD, weakness of facial muscles can be suspected
if the eyes remain slightly open when asleep, particularly in young
children, or if the eyelids cannot be screwed tightly enough to bury
the eyelashes. Difficulties in pursing the lips to whistle or to play
a woodwind or brass instrument, or in blowing up balloons, are also
suggestive of the condition. During the teenage years or in adulthood,
excessive aching around the shoulders, rounded shoulders and thin upper
arms may be the first presenting signs or symptoms.
8. Does FSHD-MD
speaking, lifespan is not affected, except perhaps in the most severe
cases with greatly impaired mobility and consequent greater risk of
chest infections. There are some recent reports suggesting an increased
association with heart rhythm disorders, but only in a few cases, and
these are responsive to appropriate medication. Because of these reports,
adults with FSHD would be advised to see their GP (or hospital doctor)
every few years for a simple heart check.
9. Will I become
in life the weakness appears the greater its eventual severity. Nevertheless,
the progression of either arm or leg weakness in the individual can
be hard to predict. Although the legs are affected to some degree in
over 50% of people, for those in whom this does not become evident until
early adulthood, even an eventual requirement for a wheelchair is unlikely.
To some extent,
knowledge of the size of the DNA rearrangement (i.e. the number of repeat
units remaining) in a person with FSHD can give a broad guide as to
whether the course of the condition would be expected to be relatively
mild or more severe.
One fairly common
feature of FSHD is an asymmetry of weakness: an uneven distribution
of muscle weakness where one side of the body is more affected than
the other (particularly early on). This is often evident in the shoulders,
usually with the right side to be the first one involved in right-handed
In what way are the legs affected?
weakness at the ankles causing foot drop is not uncommon.
Some degree of weakness at the knees or hips develops by middle age
in over 50% of people. Together with weakness in the back muscles, this
can result in a typical backward-leaning and high-stepping gait, although
only 10-20% ever requires a wheelchair.
11. Can any other
problems be anticipated?
In some of
the earliest childhood onset cases, learning difficulties and epilepsy
have been reported. Hearing loss and specific problems with blood vessels
at the back of the eye have been found, and although this rarely causes
visual problems, a periodic eye check may be useful. It is still uncertain
whether these rare features are generally associated in mild degree
with FSHD, or are limited to a few more severe cases.
Muscle pain is unfortunately
a quite frequent complaint accompanying FSHD, often in the early stages.
This may relate to inflammation within the muscles, which seems to occur
more in FSHD than other muscular dystrophies. Treatment with simple
analgesia combined with anti-inflammatory agents is usually tried, but
the effectiveness for relief can vary. Further studies are needed.
How is it inherited?
separate gene determines each hereditary characteristic or function.
These genes are packed together into chromosomes like beads on a string.
There are two copies of each chromosome (excepting the X and Y chromosomes
in males), and hence two copies of each gene (a pair), coming one from
each parent. The gene for FSHD is at one end of each copy
of chromosome 4. In FSHD, one copy of this particular pair is faulty
(part of it is missing, which is referred to as a deletion).
Hence there is a 50:50 (1 in 2) chance for each of the offspring of
an affected parent to inherit the faulty copy, resulting in FSHD. They
also have an equal chance of inheriting the good copy (resulting in
no risk for these individuals or their descendants of being affected
by FSHD). This pattern of inheritance is called autosomal dominant.
With completion of the human genome project has the gene
causing FSHD been identified?
the situation is a little more complex than as discussed (in answer
12.) above. Amongst genetic conditions, FSHD seems so far to be unique
in that the genetic fault (mutation) is the reduction (deletion
at one end of chromosome 4) of multiple copies of a repeated sequence
of DNA (likened to reducing the number of carriages in a train). This
DNA change, which is the dominantly inherited factor, is probably exerting
an effect on the way that the function of many genes is regulated in
muscle, and particularly in the muscles of the face and shoulder girdle.
Hence, there may be many genes which are involved in causing
FSHD, but for which the controlling dominantly inherited mutation always
occurs at the same place on chromosome 4. Much current research in FSHD
is aimed at trying to define this link.
14. Can FSHD
be diagnosed from a blood sample?
The DNA mutation causing FSHD can indeed be recognised from a blood
sample in most people with this condition. However, interpretation of
the test is not always easy, and the DNA sample will need to be forwarded
to one of a few molecular genetic laboratories able to offer this. In
individual cases it can be harder to exclude the diagnosis than to confirm
it, although both are usually made easier if blood samples are also
taken from both parents of a possible affected person.
In families where
there are several people known to be affected, confirmation of diagnosis,
or genetic prediction for an individual family member, will almost always
be possible if blood samples are collected from several of the affected
Is there always a family history?
A person diagnosed
with FSHD, particularly if this is in early childhood, may have a fresh
mutation (i.e. they have not inherited it from either of their parents).
More often, however, a person diagnosed with FSHD will have inherited
the faulty gene from one of his or her parents. It may be that a newly
diagnosed person finds that there is a family history, but that this
had not been recognised before because the symptoms of other family
members had been very mild, or had been misdiagnosed. We now also know
that in a significant proportion of even quite early onset cases in
children, who appear to be the first ones in a family, one of the parents
can show the same FSHD mutation in some of their cells but not in others.
This mosaic situation in the parent may not give any symptoms
in them, but does mean that further children of theirs would have a
risk of being affected. We would therefore always recommend that both
parents be invited to provide blood samples for DNA study if they wish
to know about potential risk to future children.
In other cases genetic
testing may help resolve any uncertainty over the affected status of
a young adult. Family members or couples seeking further information
should refer to their local Clinical Genetics Service.
16. How severely
affected would my sons and daughters be?
at onset of symptoms, and hence the severity of FSHD, seems to correlate
broadly with the extent of the DNA rearrangement on chromosome 4, which,
once it has arisen, remains a fixed size in a family. Thus there will
be some families where FSHD will always tend to be quite severe, and
others where it will always be relatively mild. However, there can still
be considerable variation within a family for severity and age at onset.
Partly, this is due to differences between men and women. Although men
and women develop the same symptoms, males tend to develop these earlier,
and be more severe at a given age than females. By age 30 years, just
about all males with FSHD exhibit symptoms, but only two-thirds of females
We now know that some people (particularly men) with average or mild
presentations of FSHD, may, if they are the first cases in a family,
have a mixture of normal and FSHD-type cells and their offspring, who
have inherited the FSHD mutation, would do so in all their cells, and
therefore present earlier and more severely.
Data from many families
suggests that offspring inheriting the faulty gene are likely to be
affected from a similar young age and at least as severely as occurred
in their affected parent, although in large families affected daughters
with FSH might be milder than their fathers.
At what age does it usually start?
is dependent on the extent of the DNA rearrangement. In large families
with several affected members, an affected person usually first becomes
aware of muscle weakness in teenage years or early adulthood, when he
or she experiences difficulty in raising one or both arms, or notices
prominent shoulder blades or wasting of upper arm muscles.
In the more severe
cases, which are often the first ones in a family and arising from a
new mutation giving a small residual DNA repeat length, impaired movement
of facial muscles, particularly around the mouth, can be evident by
early childhood, followed by the shoulder girdle and upper arm weakness.
In these children progressive weakness of the legs can start to develop
by teenage years and lead to the need for a wheelchair.
By contrast, in
the mildest families, with the largest residual DNA repeat lengths,
people inheriting the condition may remain unaware of symptoms until
even late in adulthood.
18. If I have
no symptoms can I still carry the gene and pass it on to my children?
person with FSHD has been affected from childhood, it is very unlikely
that an adult relative (say a brother or sister) who is unaware of any
symptoms, could carry the faulty gene or pass on FSHD to
their children. The parents of the affected child are an exception,
as they could be carrying the mutation but in only some
of their cells, and hence pass this on to more than one child.
For people from
families where several relatives or a parent have FSHD, one cannot give
the same level of reassurance except following DNA testing. In these
situations, many people at risk may be affected only mildly,
and are unaware of the abnormal signs that are present. Although some
degree of reassurance may be possible if examined by a doctor well familiar
with the condition, we now know that up to one-third of adult women
carrying the milder mutations for FSHD, and a probably much smaller
proportion of men, may not be showing any definite sign of the condition.
Therefore, the answer to this question can only be given reliably following
19. If one of
my children is affected, but another seems clear, is he or she likely
to have escaped inheriting FSHD-MD?
apparently unaffected child is several years beyond the age at which
the affected one first presented with symptoms, it becomes very likely
that they have not inherited the condition. This is particularly so
if the affected child is the first-presenting person in the family,
and if DNA testing has shown that their condition has arisen from a
new DNA rearrangement (a new mutation) not present in a DNA sample from
either parent. However, if either parent is clinically affected or carries
the mutation, only DNA testing can give reassurance. If a child has
no signs of FSHD, requests for DNA testing would normally be refused
until the child is of an age to choose this for themselves.
Can I avoid passing the faulty gene on to my children?
testing, performed by chorion villus biopsy (CVS), usually at 11 weeks
gestation, is now available to most couples who would wish this, and
whose offspring would be at risk of FSHD. It is essential that genetic
(DNA) tests be performed first on blood samples from the affected parent
or child to define the DNA mutation in that family. Blood samples would
usually be required from both parents, and in some cases from other
affected relatives. The CVS procedure is now widely available, although
the tissue sample obtained would be forwarded to one of a few specialist
genetic laboratories. Couples considering this should consult with their
local genetic service that would advise accordingly, preferably prior
to becoming pregnant.
21. Can I improve
There are no cures or specific drug treatments. Regular gentle exercise
(especially swimming) is beneficial. It is essential to keep your weight
down (through diet if necessary) in order to reduce stress on already
weakened muscles. If exercises are undertaken to increase muscle strength
any build-up should be done gradually.
Can surgery help?
muscles, which attach the shoulder blades to the chest, are often very
weak and this leads to difficulty in lifting the arms. The operation
of scapular fixation (fixing the shoulder blades to the ribs at the
back) has enabled some people to regain more use of their arms. Because
prolonged immobilisation of limbs could increase the weakness of disused
muscles, combined assessment from a neurologist and an orthopaedic surgeon
prior to operation is advised. For people who have troublesome inflammation
of the eyes as a result of them if they are remaining open at night,
surgery to bring the eyelids closer can be offered if artificial tears
alone are insufficient.
23. Are anaesthetics
There is no known risk, but you should be sure that the anaesthetist
is aware of your diagnosis prior to operation.
24. Should I
declare it on insurance forms?
Once the diagnosis has been made you have an obligation to declare it
when requested. As there is no significant effect on life span, you
should ask your doctor for a letter of support if you run into problems.
When applying for a driving licence, especially HGV or PSV, this may
be issued for a limited duration, with renewal subject to satisfactory
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