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European Journal of Forensic Sciences
Case Report
www.ejfs.co.uk
DOI: 10.5455/ejfs.180614
Sudden death due to duchenne
muscular dystrophy: A case report
Basappa Subhas Hugar1, Sunil Kumar Kainoor2,
Yashwant Kumar Singh1, Akshith Raj Shetty1
Department of Forensic
Medicine, MS Ramaiah
Medical College,
Bengaluru, Karnataka,
India, 2Department
of Forensic Medicine,
Raichur Institute of
Medical Sciences, Raichur,
Karnataka, India
1
Address for correspondence:
Dr. Basappa S Hugar,
Department of Forensic
Medicine, MS Ramaiah
Medical College, MSRIT Post,
MSR Nagar, Bengaluru –
560 054, Karnataka, India.
Phone: +919448822654/
9739325152,
Fax: +918023606213,
E-mail: basavaraj_
[email protected]
Received: February 21, 2015
Accepted: May 04, 2015
Published: July 15, 2015
ABSTRACT
Duchenne muscular dystrophy (DMD) is an inherited, progressive, neuromuscular disorder. DMD is a sex-linked
recessive disease, which results in the absence of dystrophin, a protein found inside the muscle cell membrane.
It is characterized by progressive atrophy and weakness of skeletal muscle, skeletal-spinal deformities, limb
contractures, and restrictive lung disease resulting in life-threatening pulmonary problems. Despite recent
research developments, it continues to remain as a fatal disease. One such case of sudden death in a 22-year-old
male who was diagnosed to have DMD is being reported here. He presented with a waddling gait, toe walking,
and difficulty in standing up and hence was diagnosed to have DMD at the age of 6 years. There was steady
and progressive loss of muscle strength. One day he became suddenly breathless, collapsed and died. The
death was attributed to “respiratory failure duebroncho-pneumoniaa sequel to DMD”after medico-legal autopsy.
KEY WORDS: Forensic science, forensic pathology, broncho-pneumonia, duchenne muscular dystrophy,
respiratory failure, sudden death
INTRODUCTION
The muscular dystrophies are a group of inherited, progressive
neuromuscular disorders classified on the basis of specific
phenotypic and genetic characteristics [1]. Among such
conditions, duchenne muscular dystrophy (DMD) is the
most common and most debilitating disease [2]. DMD is
named after the Italian neurologist who in 1861 recognized
the condition as a distinct disease entity [3]. It is also called
as pseudo-hypertrophic muscular dystrophy because fatty and
fibrous tissue may replace certain enlarged muscle groups [4].
DMD is an inherited X-linked recessive condition. The gene
involved in DMD is the “dystrophin gene,” largest of all the
genes ever found spanning 2.5 megabases. Deletions are the
most common mechanism to cause the disease (60% cases).
Point mutations account for up to 20% to 30% of mutations
and duplications up to 6% [5].
This condition is characterized by progressive symmetric wasting
of the leg and pelvic muscles, skeletal-spinal deformities, limb
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contractures, and restrictive lung disease resulting in lifethreatening pulmonary problems as in our case. This disease
predominantly affects males and accounts for 50% of all
muscular dystrophy diseases. It appears insidiously between 3
and 5 years of age and spreads from the leg and pelvic muscles
to the involuntary muscles. Muscles rapidly deteriorate, and calf
muscles become firm and enlarged as a result of fatty deposits.
Affected children experience contractures of the heel cords and
iliotibial bands appear, and are associated with a characteristic
waddling gait, toe walking, lordosis, and difficulty in standing
up and climbing stairs by the age of 6 and display winged
scapulae when they raise their arms. Such persons are usually
confined to wheelchairs by 12 years of age, and there will be
progressive weakening of cardiac muscle causing tachycardia
and pulmonary problems. The patients affected may also
have cardiac murmurs, faint heart sounds, and chest pain and
may suffer arrhythmias or infections that produce overt heart
failure. However, it’s chronic ventilatory failure, often with a
superimposed acute respiratory insufficiency due to pneumonia,
mucus plugging, or atelectasis, which is the frequent cause of
death in individuals with DMD. 75-90% of DMD deaths are a
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Hugar, et al.: Duchenne muscular dystrophy: A case report
direct result of pulmonary complications [6]. In all such deaths,
usually the treating physician will certify the cause of death.
Thus, an autopsy surgeon rarely comes across such deaths. One
such case of sudden death due to bronchopneumonia is being
discussed along with relevant literature review.
regenerative activity. There was a moderate increase in
endomyseal fibrofatty tissue. Immunohistochemical stain for
dystrophin was negative in the muscle fibers (diagnosis: DMD).
CASE REPORT
A 22-year-old male said to have complained of acute exacerbation
of dyspnea, he was immediately taken to a nearby hospital where
he was declared as brought dead. Due to the young age and
sudden nature of the death the case was investigated thus the
autopsy was conducted.
It was learnt from the relatives during the interview that the
deceased was suffering from chronic breathlessness. Since
1 week, it was exacerbated and was associated with cough and
fever suggestive of the respiratory infection. Further, he was
diagnosed to have been suffering from DMD since childhood
(6 years). He was born to non-consanguineous parents with
normal birth and developmental milestones, followed by
proximal muscle weakness leading to difficulty in getting
up from the floor and inability to jump and run like other
children. No history of weakness in both upper limbs and no
history of similar illness in the family. There was a hypertrophy
of calf muscles and contractures of tendoachalis. Deep tendon
reflexes were exaggerated. Gower’s sign was positive. Creatine
phosphor kinase (CPK) level was high all the time (>5000).
IQ was 85. Left quadriceps muscle biopsy revealed features of
DMD. Immunohistochemical stain for dystrophin was negative.
At autopsy the body was of 22-year-old male, moderately
built and measured 150 cm in length. There was wasting of
muscles and abdomen was scaphoid shaped, the chest was
pigeon shaped [Figure 1], and winging of the scapula [Figure 2]
Chest circumference was 76 cm, abdomen circumference was
56 cm, the mid-thigh circumference was 31 cm [Figure 3] and
calf muscle circumference (10 cm below the knee) was 28 cm
[Figure 4]. Internal examination revealed consolidation of both
the lungs. Exploration of the tracheobronchial tree showed pus
(bronchopneumonia) [Figure 5], which upon sectioning showed
patchy areas of consolidations around the bronchi and exuded
pus with admixed froth.
Figure 1: Generalised wasting of muscles with scaphoid shaped
abdomen and pigeon shaped chest
Figure 2: Generalised wasting of muscles of back resulting in winged
of scapulae
The heart weighed 255 g. Right ventricular wall thickness was
0.5 cm, left ventricular wall thickness was 1.5 cm and coronary
arteries were patent. Aorta showed fatty streaks. The stomach
contained 50 ml of brown color fluid with no unusual smell and
mucosa was normal. All other organs were intact and congested.
Histopathology examination confirmed presence of confluent
bronchopneumonia. Heart showed hypertrophic changes,
fibrosis and hyalinization of peripheral muscular fibers
[Figure 6]. Previous hospital records were procured. The
investigation reports revealed that left quadriceps muscle biopsy
showed the distortion of fascicular architecture with fall out of
myofibers in each of the fascicles, rounding with hyalinization
of fibers, prominent myonecrosis with phagocytosis and
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Figure 3: Wasting of thigh muscles (mid-thigh circumference-32 cm)
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Hugar, et al.: Duchenne muscular dystrophy: A case report
DISCUSSION
Despite recent research developments, DMD remains a
fatal neuromuscular disease. It is the second most common
genetic disorder in humans, affecting one in 3,000 live male
births [7]. 1 in 3500 of the population may be expected to
have a disabling inherited neuromuscular disease, including the
commoner forms of muscular dystrophy (Duchenne, Becker,
facioscapulohumeral, limb-girdle), myotonic dystrophy and
congenital myotonias, proximal spinal muscular atrophies, and
the hereditary motor and sensory neuropathies presenting in
childhood or in later life [8]. Boys with DMD have an absolute
absence of dystrophin, leading to deterioration of the muscle
cells and replacement with a fibrofatty tissue [9].
Figure 4: Relative hypertrophy of calf muscles (circumference-28 cm)
Figure 5: Exploration of tracheobronchial tree showing pus
(bronchopneumonia)
It is an inherited X-linked recessive condition caused by a
frameshift mutation in the dystrophin gene at the Xp21.2 locus
of the X chromosome. In approximately two-thirds of cases the
defective gene is passed on to a son through the mother’s faulty
X chromosome. In these cases, the mother is known as a “carrier”
who, in most cases, will show no symptoms of the disorder. In
only a small minority of carriers, there is a mild degree of muscle
weakness, usually limited to the shoulders and hips, and these
women are known as “manifesting carriers.” The genetic fault
may have arisen in a previous generation where there may be a
known family history. However, in approximately one-third of
DMD cases the genetic fault arises in the affected boy himself
and then it is known as a “spontaneous mutation [10].” The
present case could be due to spontaneous mutation as there was
no family history of such disease or any muscle weakness. DMD
is highly suspected in boys who have a markedly elevated serum
CPK level; in two-thirds of such patients, the diagnosis can be
confirmed by genetic testing. In our case also the CPK level
was high all the time (>5000). Large deletions or duplications
can be detected with the use of the multiplex polymerase
chain reaction and Southern blot techniques [11]. Detection
of point mutations is difficult. In patients without detectable
mutations, muscle biopsy with dystrophin analysis is necessary
for diagnosis [12,13]. In the present case left quadriceps muscle
biopsy was done at the age of 6 which revealed features of DMD.
Staining of muscle biopsy specimens with antidystrophin
antibodies in patients with DMD reveals a complete lack of
staining of sarcolemma, whereas specimens from patients with
Becker muscular dystrophy do have enough dystrophin present
so that partial staining of the sarcolemma is seen [9]. In our case,
the Immunohistochemical stain for dystrophin was negative
confirming it to be DMD.
Figure 6: Hypertrophied heart with areas of fibrosis
Finally, on perusal of autopsy findings and histo-pathological
examination report, and hospital case records the cause of
death was opined to be due to “respiratory failure as a result
of broncho-pneumonia as a sequel to DMD (Natural death).”
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Although all forms of muscular dystrophy share deterioration
of the respiratory and other skeletal muscles, respiratory
insufficiency in Duchenne follows a relentless downhill
course. Though the individual was of moderate built, there
was significant generalized wasting of skeletal muscles (except
calf muscles, which were hypertrophied) and winging of the
scapula. Abdomen was scaphoid shaped, chest was pigeon
shaped. The chest deformity as a result of progressive scoliosis
impairs pulmonary function, which is already compromised by
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Hugar, et al.: Duchenne muscular dystrophy: A case report
muscle weakness. By late adolescence, individuals with DMD
experience serious, recurrent pulmonary infections. In DMD,
death is most frequently a direct result of chronic ventilatory
failure, often with a superimposed acute respiratory insufficiency
due to pneumonia, mucus plugging, or atelectasis. 75-90% of
DMD deaths are a direct result of pulmonary complications. In
the present case also there was evidence of bronchopneumonia
at autopsy and histopathological examination.
The high incidence of illness and death in DMD from respiratory
causes is influenced by several interrelated pathophysiological
factors. Although the significance of each of the following
conditions is related closely to the extent of disease progression,
DMD patients are predisposed to the following life-threatening
complications:
• Restrictive lung disease as a result of respiratory muscle
weakness and spinal deformity.
• Ineffective cough as a result of the weakness of the muscles
of the abdomen and diaphragm.
• Immobility as a result of muscle weakness or discoordination.
• Predisposition to atelectasis as a result of secretion retention
and restrictive lung disease.
• Chronic aspiration as a result of dysphagia and exacerbated
by ineffective cough [6].
The clinical course of DMD is characterized by the development
of both spinal deformity and progressive respiratory insufficiency
secondary to failure of the breathing apparatus. Without the
muscular strength necessary to take regular deep breaths, the
lungs and chest wall stiffen, limiting the ability to take in
sufficient oxygen to meet metabolic requirements [14]. Hence
in the DMD, prognosis depends on the ventilator assistance.
With increased quality of life and prolonged survival of muscular
dystrophy patients, heart failure, and arrhythmias contribute
to a larger extent to premature death. Cardiomyopathy is first
evident on electrocardiography and echocardiography after
10 years of age. The incidence increases with age, being present
in all patients over 18 years of age. Most patients develop dilated
cardiomyopathy, sometimes preceded by localizedhypertrophy
and isolated conduction defects. In the present case, the heart
showed hypertrophic changes, fibrosis and hyalinization of
peripheral muscular fibers. Ventricular arrhythmias occur
frequently in DMD patients with impaired ventricular function
and may be an additional marker of deteriorating myocardial
function. Progressive heart disease due to congestive heart
failure or sudden death is the cause of death in 10-20% of
DMD patients, but the percentage of primary cardiac death
is expected to rise now that more successful management of
respiratory complications reduces mortality due to pulmonary
causes. Indeed, ventricular dysfunction appeared to be a
powerful predictor of mortality [15]. In all patients with Xp21
linked muscular dystrophy, a routine baseline cardiac assessment
should be done at the age of 10 years and reviewed after intervals
of 1-2 years [16].
Such complications, especially in the later stages of this disease,
can cause sudden death. Duchenne’s muscular dystrophy
usually causes death due to pulmonary or cardiac compromise
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in the second or third decade of life and within 10-15 years of
symptom onset [17]. The deceased died after 17 years after the
onset of symptoms in this case. It was evident from the history,
past medical records and autopsy findings that deceased was
suffering from DMD and had bronchopneumonia. Though the
heart showed hypertrophic changes, fibrosis and hyalinization of
peripheral muscular fibers at autopsy, the death was attributed
to bronchopneumonia since it was confluent and the death was
preceded by the symptoms suggestive of “chronic respiratory
failure, with a superimposed pneumonia.”
Although presently there is no cure for DMD, meaningful
supportive care can be provided by means of active physiotherapy
to delay the development of muscle contractures and deformities;
scoliosis management; routine airway clearance therapy to
prevent or reduce the pulmonary morbidities associated with
secretion retention; noninvasive ventilation and assisted
ventilation delivered via tracheostomy. The improvements
in general care, glucocorticoid corticosteroid treatment, noninvasive ventilatory support, and cardiomyopathy and scoliosis
management have significantly changed the course of DMD
in treated individuals, so that survival into adulthood is now a
realistic possibility for most patients [18]. The implementation
of outcome reporting for Muscular Dystrophy Association clinics
might promote the benefit of longevity of life to patients with
DMD [19].
CONCLUSION
DMD is an inherited, progressive neuromuscular disorder.
Despite recent research developments, it continues to remain
as a fatal disease. Though there is no successful treatment of the
disease, orthopedic appliances, exercise, physical therapy, and
surgery to correct contractures can help preserve mobility. These
patients may benefit from low-resistance training in which
mechanical damage is avoided and by which the metabolic and
possibly contractile properties are optimized. Several of the
reports on training effects in various types of muscle disorders
indicate that the gain in muscle function is related to the initial
muscle strength. Therefore, if muscle training regimens are to be
used, they should commence in the early stages of the disease, at
which time there is still a substantial amount of trainable muscle
tissue. When such cases are encountered in forensic practice,
it is usually as sudden death and in such cases confirmation of
the disorder will go a long way in educating the relatives and in
promoting early diagnosis of the same.
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Source of Support: Nil, Conflict of Interest: None declared.
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