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Guidelines for the Optimal Care
of Boys with
Duchenne Muscular Dystrophy |
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Consensus Report
based on the Proceedings
of an Expert Meeting in Rotterdam, 7 and 8
November 1997 |
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Foreword |
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The European branch
of the Duchenne Parent Project under the
leadership of Ms. Elizabeth Vroom
(Amsterdam) organized the first European meeting
of experts and parents with Duchenne children in
Rotterdam on 7 and 8 November 1997. One of the
aims of this meeting, chaired by Professor
Victor Dubowitz (London), was to get parents
and experts together so that the newest
developments in research for a rational cure of
Duchenne muscular dystrophy and the management
of their sons, could be explained to them
directly. The papers by the experts and the
discussions which followed have been summarized
in a report published in the scientific journal
Neuromuscular Disorders in May 1998
(volume 8, pages 213-219). Another aim was the
development of a consensus report to be used by
parents and their family doctors, which was
based on this summary and further information
and thus would be an international care standard
or guidelines for the optimal medical and social
treatment of Duchenne children.
The text of this brochure constitutes these
guidelines as of the scientific and medical
knowledge of 1998. The experts who participated
in the Rotterdam meeting worked together and
authorized this text thus making it a true
international consensus document. Two
earlier consensus reports were developed after
international expert meetings in the village of
Saig in the Black Forest in 1980 and at
the University of Aachen in Germany in
1989. Hence, this report is the third, updated
and more comprehensive, document destined to
help Duchenne families and their doctors to care
in the best way for their handicapped sons. |
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Introduction and
Basic Information |
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How to use the guidelines.
These Guidelines are full of instructions of
what to do and what not to do with boys and
young men who have the still incurable
hereditary disease Duchenne muscular
dystrophy. The enumeration of such
instructions may make these guidelines look like
the description of an imperfect technical object
which has to be maintained running as long as
possible in spite of its structural defects.
However, Duchenne boys are human beings, they
are children at the beginning and young adults
later who have a life perspective which is not
predetermined but depends to a large extent on
the way the disease is met with actions based on
decisions by the human being himself. From as
early as possible the child should be treated
as an individual person, not as an object,
by parents and his medical and social advisers.
From an early age, he can take part in making
decisions on what is good for him and what
should be avoided, provided the problems are
explained to him in an understanding and
compassionate way.
It is important that the boys understand and
accept responsibility for their own life as
early as possible. They themselves are partners
of the experts, and their wishes and decisions
are to be taken seriously from the beginning and
not only after reaching adulthood when they are
legally empowered to make all their decisions on
their own.
The guidelines present the knowledge and
opinions of many experts as they were believed
to be accurate in the first months of 1998. In
the course of time, the facts will change,
research will progress, more and better
management methods will become available, and
the whole outlook may change. This means, that
these guidelines will have to be updated from
time to time.
The chapters of this brochure are grouped
according to the different stages of the
disease, however, their age ranges may vary for
individual Duchenne boys. The topics discussed
in each chapter are those that pertain mainly to
that particular stage, but many of these topics
are important for more than one disease stage.
Some basic information precedes the
stage-specific discussions in this introductory
chapter.
Clinical course. Duchenne muscular
dystrophy is a hereditary disease which affects
mainly boys. In general, the first
clinical symptoms become obvious when they are
about 18 months to three years old: general
muscle weakness resulting in a delayed ability
to walk, problems to get up from the floor,
clumsiness while walking, difficulties climbing
stairs, abnormally enlarged calves, and even
weakness in their hands. At about 5 to 6 years,
contractures or stiffness develop in the foot,
knee and hip joints. The progressing muscle
wasting leads at about 9 to 12 years to the loss
of the walking ability. Orthopaedic operations
can delay the contractures and prolong
ambulation with long leg braces or calipers.
When walking becomes too difficult, the electric
wheelchair helps the child to regain and
maintain mobility. If necessary and desired by
the boy and his parents, a progressive scoliosis
or spine deformation can be corrected
surgically, and breathing difficulties can be
overcome first by intermittent and later, at
about 20 to 25 years, by continuous mechanical
ventilation.
The development of optimal management methods,
especially of long-term mechanical ventilation,
has increased the life expectancy of Duchenne
boys from about 15 years in the 1960s to up to
30 and in some cases to 40 years or more.
However, even now, some of the young men die
before they are 20 years old due mainly to
cardiac complications which cannot always be
overcome even with the most modern methods.
Mental retardation. Many Duchenne boys
have normal intelligence. However, dystrophin,
the protein missing in Duchenne muscles, seems
also to be important for brain function, and
Duchenne boys are missing it there, too. This
may lead to non-progressive mental retardation
and behavioral problems which demand special
attention and possibly special education.
Genetics. Duchenne muscular dystrophy is
one of the most frequent hereditary diseases in
humans and mammals. About one in four thousand
boys, independent of their ethnic origin, are
born with this disease which is caused by a
mutation or damage of the Duchenne or
dystrophin gene. The dystrophin gene was
found or localized on the X-chromosome
and its structure was determined in 1986. With
about 2.5 million base pairs or genetic
letters, it is the longest gene ever detected,
0.84 mm long when stretched out. But only 13,973
base pairs contain coding sequences, the
information for the synthesis of the
dystrophin protein. These active base pairs
are grouped into 79 regions called exons.
The much longer regions between the exons are
the introns.
In addition to their Y-chromosome, boys have
only one X-chromosome in each of their body
or somatic cells. Therefore, a damaged
dystrophin gene on the X-chromosome cannot be
compensated for, thus, the disease manifests
itself. In contrast, women have two
X-chromosomes in their somatic cells. Therefore,
an intact dystrophin gene on one of their
X-chromosomes can compensate for a damaged gene
on the other X-chromosome. Consequentely, women,
even if they have a mutated dystrophin gene,
generally do not show any clinical symptoms of
the disease. This means that Duchenne muscular
dystrophy is inherited by the X-chromosomal
recessive, or sex-linked mode and the
disease is transmitted to the next generation by
unaffected mothers, the genetic carriers.
The risk of their sons to inherit the mutated
gene and to be affected by the disease and the
probability of their daughters to inherit the
same mutation and thus to be carriers is 50% in
both cases. These risks remain the same for all
following children in a family, they are not
lower in families who already have one child
with Duchenne dystrophy. In fact, there are many
families with two and even more affected boys.
On the other hand, even in families where the
mother is a carrier, the disease might have been
unknown because no brothers or uncles were
affected or the disease was misdiagnosed in the
past.
If there is only one affected boy in the family,
it is not known whether the mother is a carrier
or not. In these cases, the disease may have
been caused by a new mutation, i.e., a
damage of the gene in the fertilized egg cell.
It is also possible that the mother has a
germline mosaic, i.e., that several egg
cells of the mother carry the mutated gene,
which is a consequence of a mutation early in
the development of the mother. Therefore, even
in these sporadic cases, the risk of having
another affected son is increased to about 7%.
Girls with Duchenne dystrophy. Girls or
women with muscular dystrophy can sometimes have
a form of Duchenne muscular dystrophy (e.g.
manifesting carriers). In these girls, the
disease can range from as severe as Duchenne in
a boy to a milder Becker-like disease. About 10%
of girls with a diagnosis of limb-girdle
muscular dystrophy have instead a
dystrophinopathy with mutations in the
dystrophin gene. Therefore, before girls with
Duchenne symptoms are treated like Duchenne
boys, a precise genetic and clinical diagnosis
has to be established.
Pathogenesis. The genetic information of
the dystrophin gene specifies the protein
dystrophin. This very large linear protein
consists of 3,685 building blocks or amino
acids, it is 125 nanometers (millionths of a
millimeter) long. In other words: 8,000
dystrophin molecules arranged head to tail would
just cover one millimeter! Dystrophin is located
on the inner side of the muscle cell membrane
and, together with several other anchor
proteins, is responsible for the mechanical
stability of the muscle cells.
In about 60% of the Duchenne boys, parts of the
dystrophin gene are missing, their gene has a
deletion, and in 5%, some regions are
duplicated. The genes of the remaining 35% of
patients have changes of single base pairs,
so-called point mutations, or very small
deletions or duplications.
The mutations may or may not disrupt the normal
reading mechanism of the genetic information. If
it is disrupted - frame-shifted -, then
the dystrophin protein will be entirely absent
or non-functional in skeletal muscle: this leads
to the severe form Duchenne: the muscle fibers
are degraded and replaced with fat and
connective tissue followed by loss of function.
When the reading frame is not disrupted in spite
of a deletion or duplication - still in-frame
-, then the dystrophin protein may be longer or
shorter or its amount reduced: it is only partly
functional and this leads to the clinically
milder Becker form of muscular dystrophy.
Therapeutic research. (Updated in
September 2002.) The aim of an effective and
long-lasting therapy is gene therapy to
transfer the active parts, the cDNA, of the
intact dystrophin gene or of parts of it into
the muscle cells or to repair the damaged gene.
Another way is a possible drug therapy to
avoid the consequences of the missing dystrophin
with more conventional medical methods. The
direct application of the protein dystrophin by
injection into the muscles or through the blood
stream is ineffective, as the large protein
cannot cross the cell membranes. Dystrophin
administration by mouth is also ineffective
because the digestive system would destroy it
completely.
A gene therapy for Duchenne muscular dystrophy
has to overcome a number of difficulties: The
newly introduced gene must become active only in
the diseased striated muscle cells. The newly
synthesized dystrophin must be anchored on the
inside of the muscle cell membrane in its
natural arrangement. The new dystrophin must not
be attacked and thus be rejected by the immune
system. And, for practical reasons, an
application of the therapeutic gene material
through the blood circulation should be possible
as otherwise the heart and respiratory muscles
could not be reached.
The first genetic therapy approach at the
beginning of the 90s was the transfer of healthy
immature muscle cells with an intact dystrophin
gene, myoblasts, by multiple injections into the
diseased muscles. This myoblast transfer
technique was effective in newborn dystrophic
neonatal mdx mice without a normal immune
system. Subsequent trials with Duchenne boys,
however, have shown that these animal
experiments could not be repeated with humans.
In several research laboratories, the transfer
of the active parts of the dystrophin gene, its
cDNA, into the muscle cells is studied by using
viruses as transport vehicles, or vectors.
Especially adeno viruses, which normally
cause only a common cold, and the smaller
adeno associated viruses are used for
transporting the full-length or the shortened
cDNA. These so-called mini genes lead to the
synthesis of shortened dystrophin which would
change the Duchenne dystrophy into the more
benign Becker dystrophy. In order to avoid an
immune reaction against the vector, in some
experiments all genes of the virus are removed
which give rise to viral proteins. Studies with
dystrophic mdx mice have shown that these
techniques could also be successful in humans
under the condition the the expected immnune
defense against the newly made dystrophin could
also be avoided.
There are other avenues of research: Plasmids
can be used as vectors, they are genetic
material from bacterial cells without proteins.
They also can transport the active parts of the
dystrophin gene. Stem cells among
myoblasts or from the bone marrow of normal mice
can migrate to the damaged parts of the muscles
and give rise to new muscle cells which then
contain the normal gene. Specific short
synthetic genetic sequences, so-called
oligonucleotides, can be used to repair some
small mutations of the dystrophin gene or to
remove entire introns flanking certain deletions
in order to restore the disturbed reading frame.
This exon skipping technique gives rise
to shortened dystrophin which however is still
sufficiently functional to lead to a slower
progressing dystrophy. Experiments in muscle
cell cultures and with mdx mice gave already
positive results. The dystrophin-like protein
utrophin, which is present in small amounts
also in Duchenne children, can, at least in
mice, compensate for the function of the missing
dystrophin. Studies are underway to
upregulate, i.e., to enhance the activity of
the utrophin gene with potential drugs. The
absence of dystrophin disturbs also the
complicated network of many other proteins which
is necessary for normal muscle function. With a
new technique, expression profiling, the
activities of thousands of genes for muscle
proteins can be studied simultaneously.
A whole series of clinical trials with Duchenne
patients are already being performed, among them
are gene transfer studies with plasmids and
trials of substances like creatine, prednisone
and many others. Some of these studies are
organized by the Cooperative International
Neuromuscular Research Group (CINRG) in
Washington with participation of clinical
centers in several countries.
This summary demonstrates that a therapy for
Duchenne muscular dystrophy is the subject of
active research projects in many laboratories.
But the time to find a cure needs to be
shortened with more laboratories becoming
involved, and this depends on more financial
support. Time is of the essence for children who
become weaker every day.
Aim: best possible state. The children
with this disease now have a much greater chance
than ever before that an effective cure will be
found during their lifetime. For this reason,
every effort should be made to keep the muscles
of all Duchenne boys remain in the best possible
state, because a future effective therapy,
although most likely to be able to stop the
further progression of muscle wasting, will
quite certainly not cause the regrowth of
muscles that have already been lost. |
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Medical and Social
Management of Boys
with Duchenne Muscular Dystrophy |
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Family doctor.
The family will need a long-term positive
relationship with a pediatrician or family
doctor who should be available for
consultations, to supervise any medical
treatment, and to work together with the
physiotherapist and other experts, like a
psychologist, his patient might need. It would
be ideal if such a doctor had special knowledge
of muscular diseases through experience with
other Duchenne boys or through special training.
S/he should know the colleagues of the next
university center for muscular diseases and the
Duchenne patient and parent organizations of
his/her country and s/he should be open to
advice from experts if that is necessary to care
for his/her patient.
Weight control. Nutrition should be
well-balanced and high in proteins and vitamins
and low in fats. Grand parents and other
visitors who are sorry for the "poor" child
should understand that chocolates, sweets, and
similar non-essential foodstuff are not in the
interest of the child. Overfeeding causes
obesity and thus constitutes an unnecessary
strain for the muscles and the heart which are
already weak. And as long as the boy is able to
walk, he should be on his feet as often
as possible.
Risks of anaesthesia. When a child with
Duchenne muscular dystrophy is subjected to
general anaesthesia, a number of serious
problems may arise. These risks can be minimized
by choosing the optimal combination of
anaesthetics, careful evaluation of the child's
respiratory and cardiac functions, and close
monitoring both during and after the operation.
The anaesthetics should definitely not include
the muscle relaxant succinylcholine and
the inhalation agent halothane as these
drugs may provoke life threatening complications
including a syndrome called malignant
hyperthermia, enhanced muscle breakdown
(rhabdomyolysis), and heart rhythm disturbances.
Non-depolarizing muscle relaxants like
vecuronium, atracurium, and
mivacuronium can be used safely albeit at a
reduced dose. Enflurane and isoflurane
instead of halothane should better be avoided.
The dosages of all other anaesthetics have to be
carefully chosen as all of them decrease cardiac
function. In children with muscular dystrophy,
cardiac function is often already compromised
especially at more advanced stages of the
disease.
As a result, it is important - and for large
operations even mandatory - to perform extensive
preoperative monitoring. Depending on the
specific situation, this screening may include a
cardiac ultrasound, an electrocardiogram,
pulmonary function tests, as well as blood gas
analyses. It is thus of utmost importance to
inform the anaesthesiologist as early as
possible of the medical history of the child.
Individual treatment: The possibilities
of treating Duchenne muscular dystrophy
presented in these guidelines neither can be nor
are they intended to be a substitute for
well-balanced therapeutic measures for each
individual child. The application and extent
of possible and obligatory therapeutic measures
depend in each case on several factors which
have to be considered carefully together with
the boy, his family, the family doctor, and the
other experts. |
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STAGE I
None or Very Slight Clinical Symptoms
Age up to about 3 Years |
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At this very early
stage, when the very first clinical signs appear
and a muscular disease is suspected, the
establishment of a precise diagnosis for
the boy is absolutely necessary. As these
guidelines will be read by parents whose son
most probably has been diagnosed already, it
should be stressed that because Duchenne
muscular dystrophy is a hereditary disease,
younger boys in the same family and in those
related through the mother, if she is a carrier,
should also be checked for the disease. However,
if the mother is proven not to be a
carrier, then only her own children are at risk
due to a possible germline mosaicism.
Clinical diagnosis: Children with
Duchenne muscular dystrophy are born without any
clinical signs or symptoms of the disease. If no
special diagnostic measures for the detection of
a muscle disease are undertaken, the disease
often remains unrecognized until the age of two
to three years or older when the grandparents,
the parents, and the family doctor - often in
this order! - detect the first development
irregularities when the child does not start
walking before 18 months, has difficulties
climbing stairs, gets up from the floor with his
hands climbing up his thighs, Gowers'
manoevre, and develops large or
hyperthrophied calves. If no muscle disease is
suspected at this stage, the families often
start a diagnostic odyssey lasting many
months while they consult one doctor after
another unsuccessfully until they are finally
able to find a specialist for neuromuscular
diseases.
The optimal treatment of a child with a muscular
disease, however, depends on an early and
precise diagnosis. Within the group of
muscular diseases there is a multitude of
different forms, characterized by different
severity of symptoms and progression, different
modes of hereditary transmission resulting in
different complications at different times: loss
of muscle force, contractures, walking
difficulties, spinal curvature or scoliosis, and
restrictions of the pulmonary function. The
differential diagnosis, i.e., the decision that
the symptoms are caused by Duchenne muscular
dystrophy and not by any other form of
neuromuscular disease relies on the results of a
number of specific diagnostic procedures.
The most simple test, which should always be
performed immediately when a muscle disease is
suspected, is the determination of the protein
creatine kinase (CK) in the blood serum.
This protein is an enzyme which plays an
important role in the transfer and storage of
chemical energy in muscles. When the muscle
membrane is damaged as in Duchenne dystrophy,
this protein and many other substances leak out
into the blood stream. As creatine kinase occurs
mainly in muscles, a consistently positive CK
test with an activity of more than 1.000
units per liter is an indication of a dystrophic
process caused possibly by Duchenne muscular
dystrophy. A high CK test result alone, however,
is not a definite diagnosis but signifies only
that the child may have a muscular dystrophy.
Then, a number of more specific diagnostic
methods are available, which should be chosen
according to the individual situation. They
should not frighten the children more than
necessary. The recording of the electrical
activity of muscles by electromyography (EMG)
hurts when needle electrodes are used, and thus
should not be done if a child has high serum CK
activities and a muscular dystrophy is clearly
suspected because of other findings such as
large calves, difficulties of walking or when
there are other Duchenne children in the same or
closely related families. EMG scans with surface
electrodes can also be used, but ultrasound
imaging of the muscle gives as much
information, is painless, and the children can
even see their own muscles on the screen.
Computer tomography scans with X-rays
should not be used in children if detailed
definition of muscle structure is desired,
magnetic resonance imaging gives similar
results without the use of damaging radiation.
In spite of the availability of genetic tests, a
muscle biopsy, i.e., obtaining a sample
of muscle tissue, is still necessary in most
cases, unless there are other unequivocally
diagnosed Duchenne children in the immediate
family. But as the modern biochemical techniques
need only very small amounts of tissue, a
needle biopsy is considered sufficient by
several investigators instead of an open biopsy.
The advantage of the needle technique is that it
can be done under local anaesthesia after
sedation with chloral hydrate. More than one
muscle sample can be obtained through the same
incision and this is sufficient for the analysis
of the protein dystrophin. Immunochemical tests
with different antibodies allow distinction
between Duchenne and other forms of muscular
dystrophy (limbgirdle and Becker dystrophies).
Molecular diagnosis: In most cases, a
Duchenne diagnosis can be confirmed in the
leukocytes of a blood sample by genetic tests
for deletions, duplications, and point mutations
in the exons and sometimes in the introns of the
dystrophin gene. Often, the details of the
deletions allow to predict the severity of the
clinical course. Following genetic counseling,
the female relatives of the Duchenne boy, i.e.
his mother and sisters, and the sisters of his
mother and their daughters etc., can also be
tested for the same deletions so that these
persons at risk can be told whether they are
genetic carriers of the disease or not. If the
mother is shown not to be a carrier, then her
sisters and other relatives are not at risk,
only her daughters have a 7% carrier risk due to
a possible germline mosaic.
If, as is the case in 35% of all Duchenne boys,
no deletion is found and there are more Duchenne
boys in the same family, polymorphic
microsatellite markers or short tandemly
repeated sequences (STR's) inside the gene and
in its neighborhood can show the inheritance of
the gene through the family without needing to
know the exact mutation itself. If a boy with
clinical symptoms and high CK activities but
without a family history has no deletion or
duplication, then a point mutation in the
dystrophin gene can be assumed. There are
several methods to test for point mutations, but
they are time consuming and expensive and
therefore not performed regularly.
Final diagnosis: Both, biopsy
investigations and genetic analyses, are
generally necessary to make the diagnosis
definite but a biopsy should not be
necessary for a second Duchenne boy in the same
family when all other clinical and biochemical
data are unequivocal. But the real final
diagnosis, as regards clinical severity and
prognosis, must always be made by an expert on a
clinical basis, because there are exceptions to
the predictive value of gene tests.
If a Duchenne muscular dystrophy has become a
certainty, it is important that the results of
the diagnostic procedures are communicated to
the parents in a compassionate way, in
private, and with sufficient time so that all
questions regarding the prognosis, the
management of their son and the consequences for
the whole family can be discussed in all
necessary detail without using non-explained
medical terminology.
Genetic counseling. After a child has
been diagnosed with Duchenne muscular dystrophy
and definitely before his parents or other
relatives related through the mother decide to
have more children, the family should seek
genetic counseling, if possible from a
geneticist specialized in neuromuscular
diseases. It is obvious that the counselor
should give them as much information as
necessary in a language they understand so that
they can make their own decisions in accordance
with their plans for the future.
The precise recurrence risk for female relatives
of a Duchenne boy depends on the exact diagnosis
of the boy and of the carrier status of those
women seeking counseling. If they have not been
performed yet, the counselor will initiate these
diagnostic procedures on request and ask that
all medical-scientific reports are made
available to him or her. The exact carrier
diagnosis is essential for each woman at risk:
those who have an increased risk for a child
with Duchenne dystrophy should be offered
prenatal diagnosis in the early stages of a
possible pregnancy. At any rate, the
significance of a risk, whether high or low,
should be explained and it should be stressed
that in spite of a low risk, it is still
possible that a new child will be affected. It
is also important to understand that the
recurrence risk remains the same for any
subsequent child in a sibship independent of
whether any other child is affected or not. The
counselor should help the parents in a
non-directive way to reach a decision on the
different options of life and family planning
when faced with an increased recurrence risk.
Responsibility for mutations. Mutations
occur as a consequence of the basic laws of
nature. These occasional changes of genetic
information were necessary for the development
of life and evolution to ever more complex
organisms. Most of these biological and physical
processes causing mutations, like e.g. cell
division and cosmic rays, cannot be altered or
influenced in any way. Therefore, no person is
responsible or can be made responsible for
damaging mutations in his or her genes. In
particular, a carrier mother is not guilty and
cannot be blamed for the mutation that caused a
hereditary disease like the Duchenne muscular
dystrophy of her son! Such an attitude would not
help at all to come to terms with the problems
of the disease.
Prenatal diagnosis. The most practical
and recommended procedure is chorionic villi
sampling (CVS), a biopsy technique with
which fetal cells are obtained from the
developing placenta by suction through the
cervix or the abdomen. This technique can be
performed as early as the 10th week of pregnancy
but has about a 1-2% risk of inducing abortion.
The genetic material obtained from the fetal
cells is then analyzed for the sex of the child.
If it is a boy, the material is tested by
molecular diagnostic methods for the same
mutation as found in the first affected child.
An amniocentesis, the withdrawal of a few
milliliters of amniotic fluid can be performed
in the 14th or 15th week of gestation with an
abortion risk of 0.5-1%. The the few fetal cells
obtained either have to be grown in culture for
about another 2-3 weeks before analytical
techniques can be performed, or they can
sometimes be used directly as explained in the
previous paragraph.
Continued consultations. During the years
following the diagnosis, contacts with
experienced medical and social experts will be
necessary at regular intervals. In these
consultations, the problem of heredity and
psychosocial conditions, such as upbringing,
school and profession, may be discussed. The
many possibilities of obtaining help should be
presented. The parents need to be assisted in
their first contacts with the local health
authorities. The organizations for handicapped
persons and their parents in the different
countries can often provide direct assistance
through their personal care services. It is also
important to establish contacts between families
who are confronted by the same problems in
personal meetings or through letter services on
a national and international level. |
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STAGE II
Slight Muscle Weakness and Beginning
Restrictions of Movement
Age about 3 to 6 Years |
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At this early stage,
the first specific symptoms of the disease
manifest themselves: reduced muscle power, first
restrictions of movements through the full
normal range of the joints. The family
pediatrician and the physiotherapist with
special knowledge of neuromuscular diseases
should work together and see it as their first
goal to enhance and to protect the individual
muscular functions of the child as long as
possible. Both should involve the parents so
that they themselves can perform the treatments
and exercises, and above all, they should let
them be the best advocates of their son because
they know him best, know what he needs, what is
best for him and what his possibilities and his
limitations are. In many instances, they will
need to make decisions in his name.
Maintenance of muscle power. According to
the child's wishes, normal physical
activities should be allowed or encouraged.
Exaggerated power training or high-performance
sports must be avoided. Walking and other
physical activities should be encouraged
according to the individual possibilities of the
child. This kind of physical stress is not only
harmless but actually beneficial. As swimming
is a useful exercise, it should be taught very
early, and any style except butterfly is
recommended; water temperatures between 28 and
31°C are preferable, but this is not always easy
to find and not absolutely necessary. Bicycle
riding on a bicycle, tricycle or on a home
trainer is recommended. Ball games of any
kind, including European football, are also
recommended. The child should be encouraged to
dress himself and to take care of his own daily
needs as far as possible independently.
The boys are still children, thus all exercises
should be presented in a playful environment,
and they should only be performed to the extent
the diminishing muscle power allows. The
physical capabilities of other children should
not be used as a goal to be reached by all
means.
The joints especially prone to early
contractures, hip, knee, and ankle, need to be
fully moved in all directions during these
activities. The children, especially those who
are inclined to be passive, have to be
"stretched". Parents should be taught to carry
out additional daily stretching exercises and
incorporate them into the child's play as much
as possible as instructed by an experienced
physiotherapist.
Unnecessary bedrest is to be avoided, e.g. in
the case of uncomplicated fever. If bedrest
should be necessary for a longer period than two
days, intermittent active exercises for the
pelvic girdle must be carried out. The child
should be brought into upright position about 5
times daily for 5 to 10 minutes.
Physiotherapy. Although there is no
consensus among the experts on the importance of
physiotherapy for boys with Duchenne muscular
dystrophy, physiotherapy may have a positive
influence on the development of muscle weakness
and delaying contractures. Physiotherapy is also
necessary to develop good balance and to
encourage the child in new activities.
Physiotherapy can only be effective as long as
the joints are freely mobile in all directions
and as long as antagonist muscles are not
shortened. Already at this early stage, at an
age of 4 to 5 years, slight restrictions of the
range of motion of the joints become apparent:
hip, knee and ankle joints can no longer be
over-extended normally and also hip adduction is
affected, i.e., the legs cannot be closed
completely. In time, the muscles become
overstrained and start to deteriorate at an ever
increasing pace.
Night splints. There is a controversy
whether ankle braces or night splints
should be recommended at this stage of the
disease, since retardation of the development of
contractures has not been scientifically proven.
Their use can be a burden for the boy and his
family. However, if they are used early on and
regularly, the child may get used to them and
the braces may possibly delay the development of
foot contractures.
Early orthopaedic intervention. When the
doctor and, above all, the physiotherapist
detect these first signs of a deterioration of
the range of motion of the joints in both legs,
it is possible to release the contractures by an
early orthopaedic intervention. The objective of
this early operation is to preserve the boy's
walking ability without technical aids
and thus his independence for as long as
possible. As the development of contractures of
the feet, knees, and hips are retarded for
several years, there is much less need for
physiotherapeutic stretching exercises, and many
of the children have been able to walk without
assistance longer than without the operation. At
the end of their independent walking ability, so
operated children can be fitted with orthoses,
as described in
stage IV,
with none or only minor additional surgical
adjustment.
In effect, there are two approaches of
orthopaedic intervention which reflect different
philosophies: the more conservative approach
with a minimum of surgery at the end of the
independent ambulatory phase at about 10 years,
or the early treatment with comprehensive
surgery at about 5 years, when symptoms are
hardly seen, but with less physiotherapy during
the independent ambulatory phase.
If the parents decide to have the early
operation performed, it is obvious that this
should only be done in centers with extensive
experience of the surgical procedure and only
when the proper follow-up examinations are
available.
In these early orthopaedic operations, the
beginning deterioration of over-extension
capacity of the hip, knee, and ankle joints, as
well as the deterioration of the pelvic range of
motion, are fully corrected by the release of
hip, knee, and ankle contractures and the
partial removal of the iliotibial band, i.e., an
operation on soft tissues and tendons only.
Afterwards, the muscles regain their optimal
work capacity. About three days after the
operation, the child is able to get up from bed
and walk around under supervision of a
physiotherapist. The operation itself is not
difficult to perform for an orthopaedic surgeon
experienced in these methods. The long scars on
the thighs have only minor cosmetic
consequences.
Steroid treatment. Several studies over
the past 10 years have shown the benefit of
prednisone in Duchenne muscular dystrophy. The
main problem has been the inevitable side
effects, especially weight gain. Most of the
problems have shown up in older children.
Recently, younger children have also been
treated and different schedules of treatment
have been introduced to try to avert the side
effects. Deflazacort, a drug similar to
prednisone, has also been tested on the grounds
of having less side effects.
The steroids prednisone and
deflazacort can delay the muscle
deterioration for several years, probably due to
their anti-inflammatory effect. In a
double-blind study in Germany, these two drugs
have been compared with the result, that
deflazacort shows less weight gain than
prednisone, but more frequent development of
cataracts. The dosis most probably to be
recommended in the future will be 0.75 mg
prednisone/kg/day or 0.9 mg deflazacort/kg/day.
As the statistical evaluation of the study is
not yet been completed, a definite
recommendation for a medication with one of
these two steroids cannot be given at this time.
If parents wish to have their Duchenne son be
treated with these drugs, they need to get
information in which centers trials are being
performed, as this type of treatment should
be done only in the context of a scientific
study.
Kindergarten. At this stage of their
disease, Duchenne boys are only very slightly
handicapped. They should go to the kindergarten
in their neighborhood like the other children,
too. The kindergarten teacher, however, should
know about the disease so that s/he can avoid
the child undergoing too much physical stress.
S/he should also explain the situation to the
other children who are normally quite willing to
accept it and to help their friend when
necessary. |
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STAGE III
Increasing Muscle Weakness and Contractures
Age about 6-10 Years |
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At this
transitional stage before the loss of the
independent walking ability, the main problems
to face are the further decrease of muscle power
and the development of increasing contractures
in the muscles of the feet, legs, and hips which
will make it more and more difficult for the
children to maintain their balance while
walking. The boys who had their beginning
contractures released will have less problems
than those without these early operations. Some
of the following suggestions thus apply only as
far as problems have to be solved.
Physiotherapy. The activities and
exercises of the early phase should be
continued. In order to strengthen the decreasing
muscle power and to treat the contractures in
the best possible way, active exercises of the
affected muscles have to be carried out on a
daily basis and with the parents' help. As
soon as contractures appear, an experienced
physiotherapist should show the parents how to
treat them twice a day by stretching the
Achilles tendon, the connective tissue band from
the iliac bone to the lower leg (iliotibial
band), and the knee-flexors. The stretching of
the muscles, ligaments, and joints should be
carried out 10 to 15 times, using each time the
full range of motion of a joint. These exercises
should last 10 seconds each time and should be
carried out slowly with the active
cooperation of the child.
Furthermore, supplementary exercises are
recommended: bending the upper body against a
wall while keeping the feet flat on the floor;
lying in prone position while reading or
watching television. The equino-varus foot
position has to be avoided by means of a support
at the ankle joint.
If at all possible, these exercises should be
incorporated into the child's playing
activities. Other activities should be
considered like playful wrestling with an adult
on the floor, therapeutic horseback riding,
European football, basketball, gymnastic ball,
and karate. These exercises enhance balance
because the children have to develop
compensatory movements to maintain balance while
walking.
All these exercises and activities need to be
carried out daily by family members and be
supervised by the physiotherapist at least twice
a month and by the family doctor every 3 months.
The physiotherapist should also make respiratory
measurements to determine a baseline and also to
watch for the signs that indicate the need for
the first or further orthopaedic interventions.
Orthopaedic measures. When the child
starts walking on tiptoes, i.e., develops an
equino-varus position of the feet, a transfer of
the tendon of a lower-leg muscle (tibialis
posterior) onto the forefoot from above can be
useful. This muscle normally moves the foot
downward. The transfer counteracts the formation
of the equino-varus deformity and permits the
child to wear normal shoes. This operation can
be performed with the later operations on the
hip, knee, and ankle joints.
Light-weight shoes with profiled soles are
useful so that the child will not fall on
slippery floors. However, special or orthopaedic
shoes are not recommended at this stage.
School: As most Duchenne boys are as
intelligent as other children, they can and
should attend a regular school. Here again, the
teachers should let all pupils and their parents
know what kind of disease Duchenne muscular
dystrophy is, that it is not contagious
and that to have such a disease is neither the
fault of the child nor of his parents.
All children should know that their weak friend
sometimes needs help but only as much as
necessary. It is important that Duchenne
children are allowed to do tasks which they are
still able to perform like writing
independently. If writing by hand becomes too
difficult, a computer should be made available
to them. To participate in sports activities
will be difficult but they should not be
excluded completely from competitive games or
other activities, e.g., they can play the role
of referee.
If at all possible, the class room should be
easily accessible by ramps or an elevator wide
enough for a wheelchair. The same is true for
the toilet rooms. It is recommended that always
one of the older students is made responsible to
take special care of the handicapped child for
one particular day.
Psychological counseling. At the age of
about 8 to 10 years, and sometimes earlier, the
children become aware what kind of disease they
have and that there is no cure. When children
start asking about death and dying, it is less
dramatic if this is handled at home or in school
as a subject of general interest that concerns
not only a child with a dangerous disease. In
many countries, conscientious objectors of
military service have to provide social
services, these young men are often the best and
most dedicated helpers of handicapped persons.
At this stage, they can become an advocate for
the child and might be available for difficult
discussions, too. In some cases the parents
might wish to have these questions answered by a
psychologist, and they themselves might also
need professional counseling to be able to
better cope with these questions and problems. |
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STAGE IV
Reduced Walking Ability
Age about 10-14 Years |
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In spite of all
management efforts, the deteriorating muscles
will make it more and more difficult for the
child to keep his balance. Independent walking
will sooner or later become impossible due to
the development of contractures and loss of
muscle strength. In order to maintain the boy in
an optimal condition as long as possible, his
walking and standing ability can be extended for
a few years by the use of long leg braces,
also called orthoses or calipers. In most cases,
an orthopaedic intervention will be necessary
before the orthoses can be used.
The child walks with stiff legs in the long leg
braces which means that the gait in the braces
is not always a practical gait for outdoor
walking. He will also need an electrical
wheelchair for moving over long distances.
However, the braces do not only give the child
the opportunity to walk indenpendently indoors.
They make the care and handling more easy for
the parents or his siblings because it is then
not necessary to lift him when he has to go to
the toilet, to the basin, to bed or to get
dressed as he can stand up by himself with only
a little help. Standing and walking with the
braces stretches the muscles that tend to
develop contractures in the legs. Therefore, it
reduces the need of physiotherapy as well. For
the child, it feels as a relief to be able to
stand up as many times a day as he wants and to
stretch the back and the legs when he would
otherwise be confined to sit in a chair.
There are, however, some experts who object
against using calipers because walking in them
is not quite normal and, therefore, rather
stressful. The use of a wheelchair is sometimes
seen as the easier solution. But the positive
consequences of the braces for the daily life of
the child and the advantages of an early use of
an electric wheelchair which allows the child to
better keep up with his peers outdoors leads to
the recommendation to use both, braces and
wheelchair at this stage of the disease.
Operative Measures: Independent
ambulation with braces or orthoses of the legs
for a limited period of time can only be
achieved by an operative release of the
contractures at both legs provided the muscles
are still sufficiently functioning for a
well-balanced trunk. But even after independent
walking with orthoses has been lost after some
time, it is still advantageous for the boy to
have joints without contractures, which
considerably facilitate his daily life
activities and further treatment.
Only if the children can still walk and stand
each day for a few hours, positive effects on
respiration can be expected and the development
of contractures and spine deformation,
scoliosis, will be retarded. For these
reasons, the boy and his family should be
interested in maintaining ambulation and
standing as long as possible and the
exclusive use of a wheelchair should be
postponed as long as possible.
The rather simple orthopaedic operation and the
fitting with orthoses should be done when the
children are at the end of their walking ability
(age about 10 years). Any contractures at the
hip, knees, or ankles have to be released by
tenotomy, i.e., release of the tendons, so that
the patient can be fitted with the orthoses or
calipers. These orthoses have to be individually
made by a specialized orthotist or orthopaedic
mechanic. A typical treatment protocol would be:
day 1, admission to the hospital and moulding
for preparation of the orthoses; day 2:
bilateral percutaneous tenotomy of the Achilles
tendon and hip flexors; day 3 to 5: bed rest;
day 6: fitting the orthoses and standing with
orthoses; day 7 and 8: assisted and free walking
in orthoses; day 9: discharge from the hospital.
It is important that bed rest during the day is
kept at a minimum. There is only little pain
after the operation, mainly at the heel, which
can be easily controlled with the usual drugs.
The children walk in orthoses with locked knees
and only on flat surfaces, they should wear them
most of the day. An upper lip on the orthoses,
on which the child "sits" while using them, is
important for keeping balance.
Control examinations: At this phase of
the disease, when the Duchenne boy often remains
in a seated position for a long time, a
scoliosis or spine deformity starts to
develop as well as a pelvic obliquity. Now, the
spine and the pelvis should be examined every 6
months so that a surgical stabilization can be
considered as early as possible at the beginning
of the next stage, the wheelchair stage. At
these control examinations, the spine must be
X-rayed from the front and from the side in an
upright sitting position.
For an early detection of disorders of the
pulmonary function, the vital capacity, i.e.,
the maximum volume of expiration after maximum
inspiration, and the peak flow, i.e., the
maximal forced expiratory flow, should be
measured at least twice a year from the age of 9
years on.
Prevention of respiratory problems: At
this point, a prophylactic respiratory
exercises are recommended along with
physiotherapy. This should be incorporated into
the child's play, if possible, and started
before the age of 9. It is important to teach
the parents how to prevent accumulation of
secretions in the airways by giving manual
support for coughing whenever needed (see
paragraph on assisted coughing below), by
letting the child change position from side to
side or to the back during the night. In case
that secretions have accumulated they can be
removed by tapping and vibration of the chest in
different body positions eventually with the
head in low position. Smoking is never
permitted in the presence of the child. If
pulmonary infections with breathing difficulties
occur at this stage, the boy has to be
hospitalized immediately.
Cardiomyopathy: The protein dystrophin is
not only missing from the skeletal but also from
the cardiac muscles, this leads in time to a
heart involvement or cardiomyopathy, and that
becomes normally the most important problem in
the late stages of the disease. Some Duchenne
boys develop early myocardial dysfunctions
before respiratory insufficiency, and it is
often difficult to determine the real problem.
Below the age of 14 years, about 15% have
significant cardiac abnormalities. The cardiac
problems of Duchenne boys, however, are
alleviated by the diminishing muscle mass which
reduces the load on the pumping capacity of the
heart.
Most Duchenne boys do not complain about cardiac
problems because they are not physically active
and their other problems are greater. But every
boy should be checked by a cardiologist yearly
from 8 years on, with echocardiography from age
10, with ultrasound and Doppler technique to
determine the myocardial contractivity from age
12. The diagnostic value of electrocardiography
is limited. Before any surgery, it is important
to evaluate cardiac function. Cardiac
insufficiency should be treated with inhibitors
of the angiotensin converting enzyme (ACE
inhibitors). Steroids for treating cardiac
problems are not recommended and a treatment
with digoxin without careful monitoring is
dangerous and can lead to severe arhythmias.
Dental problems: An imbalance between the
oral muscles and an enlargement of the tongue
may cause a crossbite of the molars in most
Duchenne boys. As this imbalance is the result
of the natural course of the disease, a
correction of this particular problem is not
recommended. |
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STAGE V
Adolescent Stage
Age about 12 to 18 Years |
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At this stage, the
diminishing muscle power will reduce the walking
ability of the boy further so that he is no
longer able to walk for a longer period without
assistance, and only short distances can be
covered without excessive fatigue. If the child
does not already have a wheelchair, the use of a
wheelchair must be considered, both for outdoor
activities as for indoors. Although the
wheelchair is often perceived as the
materialized milestone of an irreversible
process, its use, which cannot be avoided,
should not be considered as a catastrophe. It
relieves the child of much physical stress and
at this stage helps him more than it hinders him
to perform his daily activities.
Most of the boys with Duchenne muscular
dystrophy stop walking independently between 10
and 12 years. Those who still can walk without
braces at this stage may have an intermediate
form of Duchenne dystrophy or even Becker
dystrophy. It is advisable then to check their
original diagnosis by the modern methods.
The wheelchair: In most cases, an
electric wheelchair should be used from the
outset because a manual wheelchair to be powered
by the boy himself might be sufficient for a few
months only. However, a narrow and light manual
wheelchair is recommended and helpful for moving
inside the house and especially for visiting
places that are not adapted for an electrical
wheelchair.
Size and weight of the wheelchair as well as the
configuration of the wheels and their diameter
should be chosen according to body size and
preferable use, for outdoors or for indoors. It
should be possible to bring the back of the
wheelchair with the headrest into an almost
horizontal position to allow an intermittent
relaxation of the spine. It should also be
possible to tip both the backrest and the seat
backwards in one unit. The foot rests should be
adjustable individually so that the sitting
position can be changed. To keep the spine as
straight as possible and to avoid that the boy
sits asymmetrically, the lordosis of the lumbar
spine should be strongly supported and the arm
rests and the control panel of the wheelchair
should be close to the body. For safety and
comfort reasons, the wheelchair should have a
security belt with an electric tightening
mechanism.
The adolescent stage is characterized by an
increase of the existing contractures
at the hip, knee, and ankle joints as well as by
a curvature of the spine
(kyphoscoliosis). Contractures of the elbows,
wrists, and fingers will gradually also appear.
Duchenne boys who use their wheelchair
exclusively, can complain of feeling tired in
the back, pressure on the buttocks, and cold
feet. To some extent, this can be improved by a
correction of the sitting position with cushions
and by applying the electrically operated
functions of the wheelchair mentioned above
which allow the boy to change his position by
himself as often as he wishes.
Physiotherapy: At this point, the further
development of contractures of the legs
constitutes a major discomfort for the boys.
Virtually only the sitting position is available
and he can sleep only on the sides and on the
back with the knees bent and supported by
pillows. Therefore, further stretching exercises
for the muscles and tendons should be carried
out regularly to retard the progression of the
contractures also in the arms.
The physiotherapist should accompany the boy and
follow up on the therapeutic measures taken
which can increase the life expectancy and
quality considerably: scoliosis operation, and
mechanical ventilation. The role of the
physiotherapist is also to prepare the boy and
his parents for these interventions.
The young man is now old enough to decide
himself how to be treated and to be the master
of his own time. Together with the specialists,
he should decide how to integrate the physical
exercises into his daily life activities. He
should have enough time to develop and pursue
his social and intellectual abilities in a way
that would allow him to compensate as much as
possible for his physical disability.
The aim of physiotherapy is to maintain the
physical independence as far as possible by
physical exercises and by accepting all offers
of help. An ever growing series of technical
aids is able to compensate for weakness and
disabilities. As the physiotherapist is often
closer to the family than the other medical
specialists, s/he can play a mediating role,
advising when it is time for particular
interventions, e.g. the use of mechanical
respiratory aids by intermittent positive
pressure breathing (IPPB) or aids for keeping
the airways free from secretions such as
continuous positive airway pressure (CPAP). S/he
also should teach the parents assisted coughing
techniques to remove secretions and to overcome
life threatening respiratory incidents.
Respiratory management: The prognosis for
Duchenne boys, i.e. his future life, depends to
a large extent on his respiratory function.
Inspiratory and expiratory muscles are affected
by the disease and respiratory problems will
occur with or without additional spinal
deformities. The consequences are sleep
breathing disorders and frequent respiratory
infections.
The parents and their son should understand the
symptoms associated with respiratory dysfunction
and, when they are present, immediately contact
the medical experts to evaluate the need for
respiratory treatment. Respiratory dysfunction
starts with symptoms of nocturnal
hypoventilation: insomnia, nightmares, frequent
calls at night, nocturnal and morning headaches,
daytime fatigue and sleepiness, decrease of
intellectual performance, loss of appetite,
weightloss, frequent respiratory infections, and
cardiac rhythm abnormalities. Arterial blood
gases, vital capacity, and respiratory muscle
strength should be measured, and breathing
during sleep monitored. Symptoms of
underventilation with muscle strength less than
30%, vital capacity less than 50% or 1.5 liters,
a partial oxygen pressure of less than 75 mm Hg
and/or a partial carbon dioxide pressure of more
than 45 mm Hg and/or nocturnal oxygen
desaturation of less than 90% are indications
for beginning treatment. Swallowing disorders
and associated factors like obesity and smoking
put a patient at higher risk.
Treatment should begin with the education of the
parents and their son to prevent respiratory
infections, to control weight, to avoid
intestinal problems such as constipation, and to
learn assisted coughing and secretion removal
techniques. Respiratory assistance should be
started at night with a ventilator through a
nasal mask, and later, when needed, daytime
ventilation using a mouthpiece can be added. In
the earlier stages, nocturnal ventilation is
sufficient to eliminate symptoms of
underventilation. Intermittent ventilation
through a mouthpiece on demand during the day (4
to 5 times per minute) with the ventilator
installed on the wheelchair is very beneficial
at later stages. Preventive ventilation before
symptoms occur is not effective.
Treatment of underventilation with oxygen alone
is not indicated and can be dangerous!
Tracheostomy ventilation, i.e. breathing
through an opening in the windpipe, is
recommended when patients have little
respiratory autonomy and show poor results of
non-invasive ventilation or when swallowing
disorders lead to chronic aspiration of saliva
and food. Tracheostomy is very effective, but it
is not usually reversible and increases
drastically the dependency on care which might
not be available in every case.
Assisted coughing: The clearing of the
lungs from secretion normally achieved by
coughing is difficult for the Duchenne boys
whose abdominal and respiratory muscles are
severely deteriorated. Specially trained
physiotherapists know how to assist him and
should show the parents or other caregivers this
technique which may be lifesaving in an
emergency. This is very important as the
inability to cough in an emergency leads quite
often to death by suffocation.
Operative correction of scoliosis: When a
Duchenne boy starts to use the wheelchair
predominantly, the further weakening of the
muscles of the back leads to a progressive
deformation of the spine, i.e., a scoliosis
develops. This deformation cannot be corrected
by corsets but only by surgical stabilization.
Among the different surgery techniques, the most
often used are the Luque and
Cotrel-Dubousset techniques in which the
spine is stabilized by steel rods attached to
the vertebrae with loops of wire or screws. This
rather extensive operation has become routine
and up to 80% of the Duchenne boys in the
developed countries are operated in this way.
These operations should only be performed in
centers with experience and only when follow-up
over several years is assured.
At the time of spine correction, Duchenne boys
have a cardiomyopathy though mostly without
clinical signs of a cardial insufficiency.
Before surgery, it is not possible to assess the
real cardial stress tolerance caused by the
operation. It is noteworthy that during spine
surgery, the boys do not usually show left
ventricle problems but rather signs of a right
ventricle insufficiency. They also have a
platelet function deficiency in spite of a
normal bleeding time and therefore need
extensive blood transfusion during surgery and
substitution with the protease inhibitor
aprotinin.
After the operation, the boy does not need a
corset. The operation generally has no major
influence on the growth as the spine has
normally stopped growing at an age of 12 to 14
years. On the contrary, as the spine is
straightened by the operation, the children
become taller. The majority of boys and their
parents have positively evaluated the sitting
position, the cosmetic improvement, and the
quality of life after the surgical correction of
the spine. More than 90% would give their
consent for this rather extensive operation
again.
The best time for the operation is, when the
angle of the spinal curve while sitting just
exceeds 20°. A preventive operation before the
onset of scoliosis is not recommended.
Prerequisites for the operation are a good
general condition and a minimum vital capacity
of about 30% of normal. The extent of the
curvature, however, is normally not the limiting
factor for the operation. The correction of
scoliosis by spine surgery does not necessarily
increase vital capacity. However, the children
can breathe better and often need less assisted
respiration afterwards. In addition,
spondylodesis (spine fusion) during the
operation will help to minimize the secondary
chest deformities. It is important that the
scoliosis operation is followed up by adapting
the wheelchair and the height of the table to
make sure that the young man can maintain use of
his hands for eating and writing as he did
before the operation.
School and professional training: There
are many Duchenne boys who attend high school or
even university. If the proper technical aids
are available, there are practically no
limitations for a challenging education as long
as no physical power is required. Computer
programmer always comes first as a possible
profession, but there are many others like
translators, interpreters, teachers, attorneys,
telephone operators, secretaries, writers, even
politicians. The parents and the whole family
should encourage and help the boy if he wishes
to pursue a particular professional education.
In many countries, financial assistance is
available for the training of handicapped
persons.
Psychological counseling: At the onset of
puberty, Duchenne boys become aware more than
before that they will not be able to lead a
normal emotional and sexual life. Here again,
the services of a professional psychologist will
be needed. |
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STAGE VI
Adult Stage
Age more than about 18 Years |
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At this stage, most
of the skeletal muscles have deteriorated and
the young man depends on a number of technical
aids including continuous mechanical
respiration. In spite of this situation, with
the proper help, they can, if they wish and if
they have access to all necessary technical
aids, lead a meaningful and even productive
life. But long-term personal assistance would be
very helpful if it is available for those who
wish to become independent of their parents.
Specific problems. The problems that
might appear at this stage are: difficulties in
sitting upright in the wheelchair and in
controlling the head or difficulties in
operating the joystick of the wheelchair with
the hands. These problems can usually be solved
by technical adaptations of the wheelchair.
Difficulties in operating the keyboard of a
computer can also be solved by using a
minikeyboard that can be held and operated in
one hand. In the event of swallowing
difficulties a correct positioning for the
head has to be ensured; it may be necessary to
feed mashed or liquid food. These problems can
aften be solved by proper ventilation, if
necessary after tracheostomy. Sleeping
problems caused by a lack of mobility of the
body may be improved by the use of foam rubber
mattresses or a special air mattress, whose side
chambers can be inflated alternately, and
devices which avoid the pressure of the blanket
on the feet like a foot cradle.
Transportation problems can be overcome with
hydraulic lifting devices in the toilet and
bathroom; special beds which can be tilted
electrically are often indispensible.
The young men are adults. Although most
of the decisions concerning his life had to be
made by his parents, the young man with Duchenne
muscular dystrophy is now an adult. That means,
he himself can and should decide how and to what
extent to accept the suggestions of his medical
and social advisers. This is especially
important when decisions are due whether to
begin mechanical ventilation with or without a
tracheostomy. Even the most important decision,
namely whether to ask for medical emergency
measures, should they become necessary, should
be left to the young adult himself. In fact he
should make his views known and give the
corresponding instructions in a legal binding
way before emergencies arise.
School, education, professional life. As
mentioned above, there are practically no limits
for a well-maintained young man with Duchenne
muscular dystrophy, who has all necessary
technical aids, to attend school or university
or to pursue a profession as long as no physical
power is necessary. In most countries there are
laws which prohibit the discrimination of
handicapped people, and that means that all
physical barriers which would impede access must
be removed and all help provided so that people
with Duchenne muscular dystrophy can participate
in all life activities. However, an excellent
education does not automatically guarantee an
adequate working place or professional position.
It will be difficult to find work at all because
competition will be severe and rejection may
have serious consequences. Unpaid or underpaid
work may often be better than no work at all.
Sexuality: This is a very difficult
subject because Duchenne boys are sexually quite
normal but their handicap makes it almost
impossible for them to live a normal sexual
life. Not only these problems make it mandatory
that the young adults have enough privacy. This
would be easier to achieve if they were able to
live outside their parents' home in an
environment which encourages independent living
and partnerships. Although it is still an
exception, marriages or partnerships between a
man with Duchenne dystrophy and a
non-handicapped woman are known. If the female
partner is not a Duchenne carrier herself, their
children have no increased risk for Duchenne
dystrophy. The affected man would transmit his
intact Y-chromosome to all of his sons, thus the
sons would be completely free of the disease and
also would not transmit it further. All
daughters would receive the X-chromosome with
the mutation and therefore be carriers who would
then transmit the mutated gene to their children
with a risk of 50%. |
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Conclusion and
Outlook |
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Duchenne muscular dystrophy has
always been with mankind and also with all
animals which have muscles. It got its name in
the last century after the French physician
Duchenne de Boulogne described it in 1868.
From the mode of inheritance, it was known at
the beginning of this century that a defect on
the X-chromosome was responsible for the
disease, but only in 1986 was the gene itself,
the dystrophin gene, identified and
shortly afterwards the protein dystrophin,
which is missing in Duchenne boys,
characterized. The fast pace of genetic research
gave rise to an optimism that a gene therapeutic
approach would soon be able to replace the gene
and the protein and thus cure the disease.
This optimism was premature. The first clinical
studies in 1991 with a gene replacement method,
myoblast transfer, showed that a
technique which looks promising in laboratory
animals like mice was ineffective in
Duchenne boys. Now, more than a decade after the
detection of the gene, there is still no
therapy, neither for Duchenne dystrophy nor for
any other hereditary disease like cystic
fibrosis. A whole series of gene transporters,
viruses or other vectors, are being studied in
dystrophic mice and dogs. But before they can be
injected into the muscles of children, it has to
be shown that they are safe and effective first
in mice, then in dogs and finally in Duchenne
children, i.e., they must cause the
re-appearance of dystrophin at the inner face of
the muscle membrane and improve the muscle
function considerably. The next step would be
the development of a method that would allow the
application into the blood stream so that all
muscles, also those of the heart and the lung,
could be reached. All these studies will need
time-consuming experiments with large groups of
Duchenne boys. And last but not least, the
technical and economic problems of large-scale
manufacture of the therapeutic agent must be
solved.
All these requirements must be considered and
evaluated before it is possible to make any
prediction of how long it will take until a safe
and effective therapy becomes available for
children with Duchenne muscular dystrophy. The
answer to this question is the most important
one for the parents and their sons. It will
probably take several years, more like ten years
than five, until Duchenne muscular dystrophy is
conquered. This is not what has been hoped for,
that is the negative side of this difficult
problem, the positive is that there are more and
more capable and dedicated researchers in
laboratories all over the world working on a
cure: therefore, it is certain that an effective
therapy will be there, sooner or later.
Text prepared by Dr. Günter Scheuerbrandt
Im Talgrund 2, D-79874 Breitnau, Germany
E-Mail
with the help of the following experts:
Egbert Bakker, Ph.D.
Professor dr. Gert-Jan B. van Ommen
Department of Human Genetics
Leiden University
Wassenaarseweg 72
NL-2333 AL LEIDEN
Human geneticists and molecular biologists
Mary Beth Deering
2305 South Greenwood Drive
USA-JOHNSON CITY, TN 37604
Physiotherapist
Professor Denis Duboc
Service de cardiologie
Hôpital Cochin
27 rue de faubourg St. Jacques
F-75014 PARIS
Cardiologist
Professor Victor Dubowitz, M.D., Ph.D.,
F.R.C.P., D.CH.
Francesco Muntoni, M.D.
Department of Paediatrics and Neonatal Medicine
Imperial College School of Medicine
University of London
Hammersmith Hospital
Du Cane Road
GB-LONDON W12 ONN
Child neurologists
Professor Dr. med. Raimund Forst
Orthopädische Klinik
Technische Hochschule Aachen
Pauwelsstraße 30
D-52057 AACHEN
Orthopaedic surgeon
Dott. Claudia Granata
Dott. Luciano Merlini
Istituto Ortopedico Rizzoli
Via Pupilli 1
I-40136 BOLOGNA
Neurologists
Dipl.-päd. Inge Heußner-Enderle
Deutsche Gesellschaft für
Muskelkranke
Im Moos 4
D-79112 FREIBURG
Family counselor
Professor Eric P. Hoffman, Ph.D.
Judith C. T. van Deutekom, Ph.D.
Department of Molecular Genetics and
Biochemistry
University of Pittsburgh School of Medicine
Biomedical Science Tower, Room W1211
USA-PITTSBURGH, PA 15261
Molecular biologists
Dr. med.
Stefan Kochanek
Zentrum für Molekularbiologische Medizin
Universität zu Köln
Kerpener Straße 34
D-50931 KÖLN
Molecular biologist
Dr. Patrick Leger
5, rue de la chèvre
F-69370 ST. DIDIER au mont d'Or
Professor Dr. med. Bernd Reitter
Kinderklinik der Universität Mainz
Langenbeckstraße 1
D-55101 MAINZ
Child neurologist
Birgit F. Steffensen
Institut for Muskelsvind
Muskelsvindfonden
Kongsvang Allé 23
DK-8000 ÅRHUS C
Physiotherapist
J. Andoni Urtizberea, M.D.
Association Française contre les Myopathies
1, rue de l'Internationale
F-91000 EVRY
Pediatrician and Physiatrist
Professor Dr. med. Gerhard Wolff
Institut für Humangenetik und Anthropologie
Universität Freiburg/Br.
Breisacher Straße 33
D-79106 FREIBURG
Human geneticist and Psychotherapist
Financial support for the meeting and these
guidelines is gratefully acknowledged to VSB
Fonds, Welzorg; Stichting Patientenfonds, the
Netherlands and Rotary Club
Aschaffenburg-Schönbusch, Germany. |
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