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Duchenne Muscular Dystrophy

Chapter · June 2014

DOI: 10.1007/978-3-319-07500-6_1

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Chapter 1
Duchenne Muscular Dystrophy

Keywords Duchenne • Dystrophin • X-linked • Dilated cardiomyopathy

Description

Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy,

characterized by rapidly progressive muscle weakness and wasting due to degenera-
tion of skeletal and cardiac muscles. The onset of symptoms occurs in early child-
hood, and affected boys never achieve the ability to run or jump. The disease
progresses rapidly, and the patients develop a waddling gait and a positive Gowers’
sign and have difficulty in climbing stairs, with frequent falls. Loss of independent
ambulation occurs in average at 9.5 years in non-steroid-treated patients. Once
ambulation is lost, joint contractures and scoliosis develop rapidly. Cardiomyopathy
and respiratory failure are the main cause of death [1]. DMD is caused by the
absence of the sarcolemmal protein dystrophin [2], which results from mutations in
the DMD gene (Table 1.1). Diagnosis is based on the clinical picture, family history,
laboratory findings (CK is 100–200 times the normal), and a complete absence of
the dystrophin protein in muscle. Genetic analysis shows a frameshift deletion/
duplication or null mutations in the DMD gene, offering crucial data for prenatal
diagnosis.

Case Report

After an uncomplicated pregnancy, delivery, and neonatal period, motor milestones

were normal. The boy walked at 12 months and talked at 15 months. At age 2 years,
his gait seemed clumsy. In the following years, he had increasing difficulty running,

C. Angelini, Genetic Neuromuscular Disorders: A Case-Based Approach, 3

DOI 10.1007/978-3-319-07500-6_1, © Springer International Publishing Switzerland 2014
4 1 Duchenne Muscular Dystrophy

Table 1.1 Genetic data Disease symbol DMD

of DMD Disease MIM # 310200
Gene symbol DMD
Gene MIM # 300377
Protein Dystrophin
Chromosome locus Xp21.2
Inheritance X-linked recessive

walking, and climbing stairs. Examination at 8.5 years showed a waddling gait on
tiptoes, marked proximal weakness in the arms and legs, calf hypertrophy, and
severe lordosis. He could not rise from the floor or climb stairs unassisted. At
9.7 years, he could not walk. Serum CK values ranged between 8,500 and
25,000 U/L. EMG showed a myopathic pattern. Electrocardiography and echocar-
diography were normal. Intelligence was normal. The patient has never been treated
with steroids or surgical procedures.

Laboratory Exams

A quadriceps muscle biopsy at 9 years showed end-stage muscular dystrophy with

marked fiber size variation, central nuclei, active necrosis, and markedly increased
endo-perimysial connective tissue.
Dystrophin Western blot using antibodies against the proximal and central por-
tions of the rod domain gave no reaction. DNA showed an intragenic in-frame dele-
tion that involved exons 10–53.

Conclusion

Duchenne dystrophy can be due to point mutation or intragenic deletion or

duplication in the dystrophin gene. Usually, the analysis of dystrophin protein in
muscle showed absent protein, but in about 30 % of cases, occasional “revertant”
fibers can be detected [3, 4]. These partially dystrophin-positive fibers result from
spontaneously occurring reversion of the mutation in some nuclei, but their pres-
ence does not significantly influence the age at loss of ambulation.
Treatment with corticosteroids (deflazacort) is the gold standard [5].
Corticosteroids should be introduced when the child’s motor skills plateau, usually
between 5 and 7 years of age (Figs. 1.1 and 1.2). Complications of corticosteroid
therapy must be managed and include body weight management, H2 antagonists for
gastric protection, regular monitoring and treatment of osteoporosis, and ophthal-
mic assessment for cataracts and glaucoma. Regular cardiac monitoring is also
required to allow early treatment with ACE inhibitors. Surgery may be required for
correction of the scoliosis, and nocturnal BIPAP is beneficial for the treatment of
Conclusion 5

a b c d

e f g

h i

Fig. 1.1 Patients with Duchenne muscular dystrophy at different ages. Note calf hypertrophy
(a) and hypotrophy of the quadriceps muscles (b), gait on tiptoes and Achilles tendon retraction in
a steroid-treated patient with weight gain (c, d), and waddling gait in one long-walker patient (e).
Weakness and atrophy in the lower girdle muscles cause the Gowers’ maneuver (f–i): when the
patient rises from the floor, he needs to help himself with one or two hands

restrictive respiratory failure. DMD has a severe prognosis and life expectancy is
significantly reduced with death occurring in early adulthood. The use of steroids,
particularly deflazacort, has given a considerable result both in prolonging ambula-
tion and antagonizing secondary phenomenon such as respiratory insufficiency and/
or cardiomyopathy.
6 1 Duchenne Muscular Dystrophy

a b c d

e f g h

Fig. 1.2 Patients with Duchenne muscular dystrophy. Weakness and atrophy in the lower girdle
muscles cause difficulty rising from a chair (a–d) and climbing stairs (e, f). Weakness and atrophy
in the upper girdle muscles cause difficulty dressing (g) and lifting objects over the head (h)

Key Points

• Duchenne boys lose ambulation before 12 years; if treated with steroids, they
may prolong walking ability.
• Cardiomyopathy has to be monitored and treated.

References

1. Melacini P, Vianello A, Villanova C, Fanin M, Miorin M, Angelini C, et al. Cardiac and respira-
tory involvement in advanced-stage Duchenne muscular dystrophy. Neuromuscul Disord.
1996;6:367–76.
2. Hoffman EP, Brown Jr RH, Kunkel LM. Dystrophin: the protein product of the Duchenne
muscular dystrophy locus. Cell. 1987;51(6):919–28.
 References 7

3. Fanin M, Danieli GA, Vitiello L, Senter L, Angelini C. Prevalence of dystrophin-positive fibers

in 85 Duchenne muscular dystrophy patients. Neuromuscul Disord. 1992;2:41–5.
4. Fanin M, Danieli GA, Cadaldini M, Miorin M, Vitiello L, Angelini C. Dystrophin-positive
fibers in Duchenne dystrophy: origin and correlation to clinical course. Muscle Nerve.
1995;18:1115–20.
5. Angelini C, Pegoraro E, Turella E, Intino MT, Pini A, Costa C. Deflazacort in Duchenne
dystrophy: study of long-term effect. Muscle Nerve. 1994;17(4):386–91.

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