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Duchenne Muscular Dystrophy
Sections of this chapter were written with the collaboration of Association Française Contre les Myopathies
(AFM) and the Duchenne Family Support Group (UK).
Clinical Picture
DMD
Duchenne Muscular Dystrophy (DMD) is one of the most frequent
hereditary diseases. It is a degenerative genetic disease caused by a mutation
of the dystrophin gene located on the X chromosome leading to an absence
of dystrophin, a protein that helps keep muscles intact. As an X-linked
recessive disease, it affects mainly boys. Its estimated prevalence is one
in 3 500 males. DMD symptoms usually begin in childhood causing general
muscle weakness, resulting in clumsiness while walking, problems getting
up, difficulties climbing stairs, abnormally enlarged calves and even
weakness in the hands. At about 5 to 6 years old, contractures or stiffness
develop in the foot, knee and hip joints. The progressive muscle wasting
leads, at about 9 to 11 years of age, to the loss of the ability to walk.
Orthopaedic operations are often
necessary to correct the contractures
or spine deformation. When walking
becomes too difficult, an electric
wheelchair helps the child to regain
mobility and independence. DMD
progresses severely, eventually
affecting all voluntary muscles,
as well as involuntary muscles, such
as the heart and breathing muscles.
Life expectancy has increased during
Luc and Francis, Duchene Muscular Dystrophy
© Renault family.
the last decades thanks to optimal
management methods. For example,
breathing difficulties can be overcome by intermittent and later continuous,
mechanical ventilation. However, due to cardiac or other complications life
can be significantly shortened in patients with DMD. Most boys with DMD
have normal intelligence, but some have learning or behavioural difficulties.
Women can be carriers of DMD, but usually do not exhibit symptoms.
A small number of female carriers of the gene can experience milder symptoms
and are often called ‘manifesting carriers’. Although no cure is yet available,
symptomatic treatments, which include orthopaedic, respiratory and cardiac
therapies, help with many complications. DMD is also the subject of many
research projects and clinical trials in drug and gene therapies, whose aims
are to identify a more effective and long-lasting therapy.
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Living With Duchenne Muscular Dystrophy
Because DMD is usually detected early, a parent’s perspective reveals a great
deal about living with the disease. Discovering that one’s child has DMD can
be a considerable shock especially when, in infancy, the child can appear to
be normal and healthy. Parents are encouraged to learn as much about the
disease as soon as possible and engage in discussions for a long-term plan for
follow-up. The better parents are informed about DMD, the more quickly
they can implement helpful solutions when needs arise for their child.
Some patients with DMD begin having difficulty walking at the age of 1 to 3
years old. However, this is not always the case and some patients continue
walking for some time longer and attend school. At about 8 to 11 years of
age, patients become unable to walk. With the aid of wheelchairs as well as
possible structural alterations to school facilities, school
continues to be a possibility. In the home, structural changes
may be necessary as children slowly lose the ability to dress
‘“Go faster; climb the stairs,
concentrate” … the remorse
and bathe themselves and moving around the house becomes
caused by misplaced
increasingly difficult. However, with careful preparation,
demands is rarely discussed.’
Parent of Louis, France
modifications can be quickly made to adapt to the changing
situation of the child.
Patients with DMD must be encouraged to develop
independence of thought and make choices, and mistakes, on
their own so that the loss of physical independence is mitigated. Activities
such as painting, playing a musical instrument, reading and using a computer
cannot be overestimated as beneficial outlets for creativity and selfexpression for patients living with DMD. By their late teens or early 20s, the
condition is severe enough to shorten life expectancy. Patients and their
families must also live with the reality and psychological burden of an early
death. In families with multiple siblings, parents are encouraged to reassure
unaffected children by answering their questions openly and honestly.
Parents themselves are encouraged to speak to other families with the
diagnosis for support.
Diagnosis of Duchenne Muscular Dystrophy
PARTICIPANTS IN THE SURVEY
Responses from 913 families of DMD patients
from 13 countries were analysed (Figure 1).
The majority of respondents were male
(97%). The median age of patients at
diagnosis was 4 years, with a low
variability: 25% of patients diagnosed
before 3 years and 25% were diagnosed
after 6 years of age.
Figure 1 Survey participants
affected by DMD
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AWAITING DIAGNOSIS
Due to the age of onset of the disease, neonatal diagnoses were rare (5.2%)
resulting from other cases in the family in 50% cases, but also from neonatal
testing (one in three). Not including neonatal diagnoses, the time elapsed
between the first clinical manifestations and diagnosis was 16 months for
50% of patients (less than six months for 25% of patients and more than
three years for another 25% of diagnoses).
During the quest for diagnosis, 88% of families consulted one to five
physicians, and 10% of families consulted six to ten physicians. A significant
number of various examinations and tests (biological testing, 76%; genetic
testing, 39%; X-rays, 22%; and functional testing, 40%) were then
performed. Before obtaining the DMD diagnosis, another diagnosis was
given to 30% of patients. Although misdiagnosis for patients with DMD
occurred in a lower percentage of patients than that observed overall for
the 16 surveyed diseases (41%), it results in a significantly delayed diagnosis
(twice as long as for another somatic diseases and three times as long in case
of psychological or psychiatric diagnoses).
Inappropriate treatments resulting from misdiagnoses occurred in 54% of
patients (medical, 12%; surgical, 5%; or psychiatric, 10%). For 55% of
the families, a delay in diagnosis was considered responsible for deleterious
consequences. The more frequent consequences included maladapted family
behaviour (18%) (e.g. complaint or punishment for a boy ‘medically
diagnosed’ as lazy) and a lack of confidence in medicine.
Consequences were associated with longer delay in diagnosis (four times
longer) (Figure 2).
Lack of confidence in medicine
Inadapted behaviour
Birth of other affected children
Figure 2 Consequences of
delays in diagnosis in DMD
patients.
Death
Cognitive
Psychological
Physical
0%
10%
20%
DMD
30%
all
DIAGNOSIS
Diagnosis of DMD was obtained on the basis of biological (39%), clinical
(23%) and genetic (17%) data. The structure providing the diagnosis was
usually a specialised centre (24%) or another hospital structure (64%)
located in another region or country for 29% of families, and for which
contact details were obtained from non-medical sources in 25% of cases.
Access to diagnosis required a financial contribution from 44% of families,
and was considered as high or very high by 10% of these.
A second opinion was sought by 23% of patients to confirm the diagnosis.
Confirmation occurred in a private practice more often (13%) than for the
first diagnosis (7%).
Results
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DMD
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ANNOUNCEMENT OF DIAGNOSIS
Communication of the diagnosis occurred during a standard private
consultation in 72% of cases, but also by telephone (6%) or in written form
without explanation (10%). For 20% of patients, the diagnoses were given
without information on the disease. When provided, the sources were
medical in 66% of cases, but also patient organisations 20% of the time.
Psychological support accompanied 32% of the announcements of
the diagnosis and was provided
by a psychologist (9%),
Figure 3
another health professional
Satisfaction with
(12%) or a patient
conditions under
which diagnosis was
organisation member (6%).
announced
to DMD
Almost all families (92%)
patients.
reported that this support
should be systematically
proposed.
acceptable
well-adapted
poor
unacceptable
GENETIC ASPECTS
The genetic nature of the disease was explained to families in 87% of cases.
Genetic counselling was provided for 76% of families, keeping in mind that
in 5% of cases the consequence of delay in diagnosis was
‘Duchenne muscular dystrophy
the birth of another affected boy. Whether based on the
is usually diagnosed late, at the
age of 5 or 6. A second, even
suggestion of a health professional (66%) or not, this
a third child, or a cousin may
information was communicated to the family in 91% of
already have been born before
the first has been diagnosed
cases and resulted in the detection of carriers of the
with the disease. Imagine the
defective gene in 26% of cases and diagnosis of a relative
consequences for the family!’
Parent of Louis, France
already showing symptoms (5%) or not (3%).
Reactions to the Results
Diagnosis of DMD is technically very simple. It can, however, be easily
missed as the onset of the disease is in early childhood, after the child has
begun to walk. This makes symptoms such as new difficulty in walking
difficult to recognise as symptoms of DMD. Sometimes when children with
DMD have associated cognitive impairment, psychological misdiagnoses are
inappropriately made, leading to delays in obtaining the correct diagnosis.
The worst consequence of a delayed diagnosis is the birth of other affected
children. Taking care of a baby and an older child with DMD is very demanding.
Parents are ‘on call’ day and night. Neonatal diagnosis is possible, simple
and inexpensive and can prevent the consequences of a delayed diagnosis.
The announcement of the diagnosis is always a shock, and as such should be
given under appropriate conditions — never standing in a corridor.
The announcement of the disease may need to be delivered over several sessions,
as adequately communicating all the necessary information is very difficult
in one sitting. Competent psychologists with knowledge of genetic diseases
with serious prognoses should systematically propose psychological support.